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  • 1.
    Aeinehband, Shahin
    et al.
    Karolinska Institutet.
    Lindblom, Rickard P. F.
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khademi, Mohsen
    Karolinska Institutet.
    Olsson, Tomas
    Karolinska Institutet.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Darreh-Shori, Taher
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0122048Article in journal (Refereed)
    Abstract [en]

    Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  • 2.
    Darreh-Shori, Taher
    et al.
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Aeinehband, Shahin
    Karolinska University Hospital Solna.
    Piehl, Fredrik
    Karolinska University Hospital Solna.
    Lindblom, Rickard P. F.
    Karolinska University Hospital Solna.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Långström, Bengt
    Uppsala University;Imperial College, UK;Odense University Hospital, University of Southern Denmark, Denmark.
    Almkvist, Ove
    Karolinska Institutet;Stockholm University.
    Nordberg, Agneta
    Karolinska Institutet;Karolinska University Hospital Huddinge.
    Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 11, p. 2465-2481Article in journal (Refereed)
    Abstract [en]

    Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE-K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1 beta, and tumor necrosis factor (TNF)-alpha. BCHE-K noncarriers displayed 100%-150% higher glial fibrillary acidic protein and 64%-110% higher S100B than BCHE-K carriers, who, in contrast, had 40%-80% higher interleukin-1b and 21%-27% higher TNF-alpha compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low beta-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-alpha and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of astroglial function is a beneficial response, rather than a disease-driving mechanism. Further studies are needed to explore the therapeutic potential of manipulating BuChE activity or astroglial functional status. (C) 2013 Elsevier Inc. All rights reserved.

  • 3.
    Della Santina, Siddhartha
    Linnaeus University, Faculty of Business, Economics and Design, School of Design.
    Reasons of the Heart: Art and the shaping of modern politics2012Conference paper (Other academic)
    Abstract [en]

    Since the advent of what Germain Bazin famously described as the “museum age”, many have argued  that “art”, as a mode of creative production rooted in aesthetics, has become increasingly rarified, institutionalized and entangled in the politics and sociology of taste, making it a poor medium for critical appraisal of social or political issues. Drawing primarily on the history of the development of modern art, Terry Eagleton’s thesis on the advent of the aesthetic as a philosophical category advanced in The Ideology of the Aesthetic, and modern theories of mind which root rationality in the senses, I will argue that, notwithstanding the undisputed “entertainment” value of art, and its commercialization, the differentiation between aesthetic-­‐artistic knowledge and rational-­‐scientific knowledge might not be so simple to sustain, and that art thus serves a fundamental, if often unnoticed function in shaping social and political values in the contemporary world. 

  • 4.
    Egeland, Jens
    et al.
    Vestfold Hosp Trust, Norway ; Univ Oslo, Norway.
    Lovstad, Marianne
    Univ Oslo, Norway ;Sunnaas Rehabil Hosp, Norway.
    Norup, Anne
    Copenhagen Univ Hosp, Denmark.
    Nybo, Taina
    Univ Helsinki, Finland ; Helsinki Univ Hosp, Finland.
    Persson, Bengt A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Rivera, Diego Fernando
    Surcolombiana Univ, Colombia.
    Schanke, Anne-Kristine
    Univ Oslo, Norway ; Sunnaas Rehabil Hosp, Norway.
    Sigurdardottir, Solrun
    Sunnaas Rehabil Hosp, Norway ; Univ Oslo, Norway.
    Arango-Lasprilla, Juan Carlos
    Cruces Univ Hosp, Spain ; Univ Deusto, Spain.
    Following international trends while subject to past traditions: neuropsychological test use in the Nordic countries2016In: Clinical Neuropsychologist (Neuropsychology, Development and Cognition: Section D), ISSN 1385-4046, E-ISSN 1744-4144, Vol. 30, p. 1479-1500Article in journal (Refereed)
    Abstract [en]

    Objective: Historically, the neuropsychological test traditions of the four Nordic countries have spanned from the flexible and qualitative tradition of Luria-Christensen to the quantitative large battery approach of Halstead and Klove-Matthews. This study reports current test use and discusses whether these traditions still influence attitudes toward test use and choice of tests. Method: The study is based on survey data from 702 Nordic neuropsychologists. Results: The average participant used 9 tests in a standard assessment, and 25 tests overall in their practice. Test use was moderated by nationality, competence level, practice profile, and by attitude toward test selection. Participants who chose their tests flexibly used fewer tests than those adhering to the flexible battery approach, but had fewer tests from which to choose. Testing patients with psychiatric disorders was associated with using more tests. IQ, memory, attention, and executive function were the domains with the largest utilization rate, while tests of motor, visual/spatial, and language were used by few. There is a lack of academic achievement tests. Screening tests played a minor role in specialized assessments, and symptom validity tests were seldom applied on a standard basis. Most tests were of Anglo-American origin. Conclusions: New test methods are implemented rapidly in the Nordic countries, but test selection is also characterized by the dominating position of established and much researched tests. The Halstead-Reitan and Luria traditions are currently weak, but national differences in size of test batteries seem to be influenced by these longstanding traditions.

  • 5.
    Ferreira, Marisa Borges
    et al.
    University of Minho, Portugal;Association “Todos com a Esclerose Multipla (TEM)”, Portugal.
    Pereira, Paulo Alexandre
    Association “Todos com a Esclerose Multipla (TEM)”, Portugal;University of Minho, Portugal.
    Parreira, Marta
    Association “Todos com a Esclerose Multipla (TEM)”, Portugal.
    Sousa, Ines
    University of Minho, Portugal.
    Figueiredo, José
    Association “Todos com a Esclerose Multipla (TEM)”, Portugal.
    Cerqueira, João José
    University of Minho, Portugal;Hospital de Braga, Portugal.
    Macedo, António Filipe
    Linnaeus University, Faculty of Health and Life Sciences, Department of Medicine and Optometry. University of Minho, Portugal.
    Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients2018In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 6, p. 1-18, article id e5737Article in journal (Refereed)
    Abstract [en]

    Background

    The Stroop test is frequently used to assess deficits in inhibitory control in people with multiple sclerosis (MS). This test has limitations and antisaccade eye movements, that also measure inhibitory control, may be an alternative to Stroop.

    Objectives

    The aim of this study was twofold: (i) to investigate if the performance in the antisaccade task is altered in patients with MS and (ii) to investigate the correlation between performances in neuropsychological tests, the Stroop test and the antisaccade task.

    Methods

    We measured antisaccades (AS) parameters with an infrared eye tracker (SMIRED 250 Hz) using a standard AS paradigm. A total of 38 subjects diagnosed with MS and 38 age and gender matched controls participated in this study. Neuropsychological measures were obtained from the MS group.

    Results

    Patients with MS have higher error rates and prolonged latency than controls in the antisaccade task. There was a consistent association between the Stroop performance and AS latency. Stroop performance but not AS latency was associated with other neuropsychological measures in which the MS group showed deficits.

    Conclusions

    Our findings suggest that AS may be a selective and independent measure to investigate inhibitory control in patients with MS. More studies are necessary to confirm our results and to describe brain correlates associated with impaired performance in the antisaccade task in people diagnosed with MS.

  • 6.
    Garbarini, Francesca
    et al.
    Univ Turin, Italy.
    Riccardo, Boero
    Los Alamos Natl Lab, USA.
    Francesco, D'Agata
    Univ Turin, Italy.
    Bravo, Giangiacomo
    Linnaeus University, Faculty of Social Sciences, Department of Social Studies.
    Cristina, Mosso
    Univ Turin, Italy.
    Franco, Cauda
    Univ Turin, Italy.
    Sergio, Duca
    Koelliker Hosp, CCS FMRI, Turin, Italy.
    Giuliano, Geminiani
    Univ Turin, Italy.
    Katiuscia, Sacco
    Univ Turin, Italy.
    Neural Correlates of Gender Differences in Reputation Building2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e106285-Article in journal (Refereed)
    Abstract [en]

    Gender differences in cooperative choices and their neural correlates were investigated in a situation where reputation represented a crucial issue. Males and females were involved in an economic exchange (trust game) where economic and reputational payoffs had to be balanced in order to increase personal welfare. At the behavioral level, females showed a stronger reaction to negative reputation judgments that led to higher cooperation than males, measured by back transfers in the game. The neuroanatomical counterpart of this gender difference was found within the reward network (engaged in producing expectations of positive results) and reputation-related brain networks, such as the self-control network (engaged in strategically resisting the temptation to defect) and the mentalizing network (engaged in thinking about how one is viewed by others), in which the dorsolateral prefrontal cortex (DLPFC) and the medial (M)PFC respectively play a crucial role. Furthermore, both DLPFC and MPFC activity correlated with the amount of back transfer, as well as with the personality dimensions assessed with the Big-Five Questionnaire (BFQ-2). Males, according to their greater DLPFC recruitment and their higher level of the BFQ-2 subscale of Dominance, were more focused on implementing a profit-maximizing strategy, pursuing this target irrespectively of others' judgments. On the contrary, females, according to their greater MPFC activity and their lower level of Dominance, were more focused on the reputation per se and not on the strategic component of reputation building. These findings shed light on the sexual dimorphism related to cooperative behavior and its neural correlates.

  • 7.
    Gunnarsson, Helena E. M.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Neron HSU AB, Osby.
    Grahn, Birgitta
    Lund University ; Reg Skåne ; Reg Kronoberg.
    Agerström, Jens
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Impaired psychomotor ability and attention in patients with persistent pain: a cross-sectional comparative study2016In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 9, p. 825-835Article in journal (Refereed)
    Abstract [en]

    Background and aims: Patients with pain have shown cognitive impairment across various domains. Although the pain qualities vary among patients, research has overlooked how cognitive performance is affected by the duration and persistence of pain. The current study sought to fill this gap by examining how qualitatively different pain states relate to the following cognitive functions: sustained attention, cognitive control, and psychomotor ability. Patients and methods: Patients with musculoskeletal pain in primary care were divided into three pain groups: acute pain (duration <3 months), regularly recurrent pain (duration >3 months), and persistent pain (duration >3 months). These groups were then compared with healthy controls. The MapCog Spectra Test, the Color Word Test, and the Grooved Pegboard Test were used to measure sustained attention, cognitive control, and psychomotor ability, respectively. Results: Patients with persistent pain showed significantly worse sustained attention and psychomotor ability compared with healthy controls. The acute pain group showed a significant decrease in psychomotor ability, and the regularly recurrent pain group showed a significant decrease in sustained attention. These results remained unchanged when age, education, and medication were taken into account. Conclusion: Persistent musculoskeletal pain seems to impair performance on a wider range of cognitive tasks than acute or regularly recurrent pain, using pain-free individuals as a benchmark. However, there is some evidence of impairment in psychomotor ability among patients with acute pain and some impairment in sustained attention among patients with regularly recurrent pain.

  • 8.
    Hagman, Göran
    et al.
    Karolinska Institutet.
    Solomon, Alina
    University of Eastern Finland, Kuopio, Finland.
    Kårehult, Ingemar
    Karolinska Institutet.
    Vuorinen, Miika
    University of Eastern Finland, Kuopio, Finland.
    Håkansson, Krister
    Karolinska Institutet.
    Soininen, Hilkka
    University of Eastern Finland, Kuopio, Finland.
    Kivipelto, Miia
    Karolinska Institutet.
    Midlife hopelessness and white matter lesions two decades later: A population-based study2010In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 7, no 4, Supplement, p. 595-595Article in journal (Other academic)
    Abstract [en]

    Background: Hopelessness has been associated with increased cardiovas- cular disease mortality and morbidity, subclinical atherosclerosis and meta- bolic syndrome. This study investigates the relation between midlife hopelessness and white matter lesions (WMLs) 20 years later in a Finnish population of men and women. Methods: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study in Finland were derived from random, population-based samples previously surveyed in 1972,1977, 1982 or 1987. In 1998, 1449 (73%) individuals aged 65-79 years participated in the re-examination. A subgroup (n1⁄4112, including 39 dementia cases, 31 mild cognitive impairment (MCI) cases and 42 con- trols) underwent 1.5T MRI scanning at re-examination, and WMLs were as- sessed from FLAIR-images using a semi-quantitative visual rating scale. Hopelessness was measured by 2 questionnaire items (expectations about future and reaching goals). Results: Subjects with increased hopelessness had a significantly higher risk of developing more severe WMLs two de- cades later. OR (95% CI) was 4.35 (1.36-13.46) in ordinal regression anal- yses adjusted for age, sex education, follow-up time, presence of the APOEe4 allele, systolic blood pressure, BMI, history of stroke, heart infarct, smoking and level of midlife leisure physical activity. Conclusions: Higher levels of hopelessness at midlife seem to be related to more severe WMLs later in life. Since WMLs may contribute to late-life cognitive impairment, lifestyle management of midlife vascular risk factors (which also increase the risk of dementia and cognitive impairment) may have better effects if people’s expectations are more thoroughly discussed.

  • 9.
    Hamlett, Eric D.
    et al.
    Medical University of Southern Carolina, USA ; University of Denver, USA.
    Goetzl, Edward J.
    Jewish Home of San Francisco, USA ; University of California, USA.
    Ledreux, Aurélie
    Medical University of Southern Carolina, USA ; University of Denver, USA.
    Vasilevko, Vitaly
    University of California, USA.
    Boger, Heather A.
    Medical University of Southern Carolina, USA.
    LaRosa, Angela
    Medical University of Southern Carolina, USA.
    Clark, David
    Medical University of Southern Carolina, USA.
    Carroll, Steven L.
    Medical University of Southern Carolina, USA.
    Carmona-Iragui, María
    Biomedical Research Institute Sant Pau, Spain ; Down Medical Centre, Spain.
    Fortea, Juan
    Biomedical Research Institute Sant Pau, Spain ; Down Medical Centre, Spain.
    Mufson, Elliott J.
    Barrow Neurological Institute, USA.
    Sabbagh, Marwan
    Barrow Neurological Institute, USA.
    Mohammed, Abdul K. H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet.
    Hartley, Dean
    Alzheimer's Association, USA.
    Doran, Eric
    University of California, USA.
    Lott, Ira T.
    University of California, USA.
    Granholm, Ann-Charlotte
    Medical University of Southern Carolina, USA.
    Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome2017In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 5, p. 541-549Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid-β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD.

    METHODS: AD neuropathogenic proteins Aβ1-42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls.

    RESULTS: Neuronal exosome levels of Aβ1-42, P-T181-tau, and P-S396-tau were significantly elevated in individuals with DS compared with age-matched controls at all ages beginning in childhood. No significant gender differences were observed.

    DISCUSSION: These early increases in Aβ1-42, P-T181-tau, and P-S396-tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.

  • 10.
    Harmat, László
    et al.
    Karolinska Institutet.
    de Manzano, Örjan
    Karolinska Institutet.
    Theorell, Töres
    Karolinska Intitutet.
    Högman, Lennart
    Stockholm University.
    Fischer, Håkan
    Stockholm University.
    Ullén, Fredrik
    Karolinska Institutet.
    Physiological correlates of the flow experience during computer game playing2015In: International Journal of Psychophysiology, ISSN 0167-8760, E-ISSN 1872-7697, Vol. 97, no 1, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Flow is the subjective experience of effortless attention, reduced self-awareness, and enjoyment that typicallyoccurs during optimal task performance. Previous studies have suggested that flow may be associated with anon-reciprocal coactivation of the sympathetic and parasympathetic systems and, on a cortical level, with astate of hypofrontality and implicit processing. Here, we test these hypotheses, using the computer gameTETRIS as model task. The participants (n= 77) played TETRIS under three conditions that differed in difficulty(Easy b Optimal b Difficult). Cardiac and respiratory activities, and the average oxygenation changes of theprefrontal cortexwere measured continuously with functional near infrared spectroscopy (fNIRS) during performance.The Optimal condition was characterized by the highest levels of state flow, positive affect, and effortlessattention. The associations between self-reported psychological flow and physiological measures were investigatedusing a series of repeated measures linear mixed model analyses. The results showed that higher flowwas associated with larger respiratory depth and lower LF. The higher respiratory depth during high flow isindicative of a more relaxed state with an increased parasympathetic activity, and thus provides partial supportfor the main hypotheses. There was no association between frontal cortical oxygenation and flow, even at liberalthresholds; i.e. we found no support that flow is related to a state of hypofrontality.

  • 11.
    Hokkanen, Laura
    et al.
    Univ Helsinki, Finland.
    Lettner, Sandra
    Hosp Sisters Char, Austria.
    Barbosa, Fernando
    Univ Porto, Porto, Portugal.
    Constantinou, Marios
    Univ Nicosia, Cyprus.
    Harper, Lauren
    Rivendell Tyrone & Fermanagh Hosp, UK.
    Kasten, Erich
    MSH Univ Appl Sci & Med Univ, Germany.
    Mondini, Sara
    Univ Padua, Italy.
    Persson, Bengt A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Varako, Nataliya
    Lomonosov Moscow State Univ, Russia.
    Hessen, Erik
    Univ Oslo, Norway;Akershus Univ Hosp, Norway.
    Training models and status of clinical neuropsychologists in Europe: Results of a survey on 30 countries2019In: Clinical Neuropsychologist (Neuropsychology, Development and Cognition: Section D), ISSN 1385-4046, E-ISSN 1744-4144, Vol. 33, no 1, p. 32-56Article in journal (Refereed)
    Abstract [en]

    Objective: The aims of the study were to analyze the current European situation of specialist education and training within clinical neuropsychology, and the legal and professional status of clinical neuropsychologists in different European countries. Method: An online survey was prepared in 2016 by a Task Force established by the European Federation of Psychological Associations, and representatives of 30 countries gave their responses. Response rate was 76%. Results: Only three countries were reported to regulate the title of clinical neuropsychologist as well as the education and practice of clinical neuropsychologists by law. The most common university degree required to practice clinical neuropsychology was the master's degree; a doctoral degree was required in two countries. The length of the specialist education after the master's degree varied between 12 and 60 months. In one third of the countries, no commonly agreed upon model for specialist education existed. A more systematic training model and a longer duration of training were associated with independence in the work of clinical neuropsychologists. Conclusions: As legal regulation is mostly absent and training models differ, those actively practicing clinical neuropsychology in Europe have a very heterogeneous educational background and skill level. There is a need for a European standardization of specialist training in clinical neuropsychology. Guiding principles for establishing the common core requirements are presented.

  • 12.
    Håkansson, Krister
    et al.
    Karolinska Institutet.
    Helkala, Eeva-Liisa
    University of Kuopio,, Kuopio, Finland.
    Soininen, Hilkka
    University of Kuopio,, Kuopio, Finland.
    Nissinen, Aulikki
    National Institute for Health and Welfare, Helsinki, Finland.
    Mohammed, Abdul K. H.
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Education, Psychology and Sport Science. Karolinska institutet.
    Winblad, Bengt
    Karolinska Institutet.
    Kivipelto, Miia
    Karolinska Institutet.
    Perceived marital problems in midlife are associated with cognitive health in later life2010In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 7, no 4, Supplement, p. 595-595Article in journal (Other academic)
  • 13.
    Håkansson, Krister
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet ; Stockholm University.
    Ledreux, Aurelie
    Karolinska Institutet ; Medical University of South Carolina, USA.
    Daffner, Kirk
    Harvard Medical School, USA.
    Terjestam, Yvonne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Bergman, Patrick
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Carlsson, Roger
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Kivipelto, Miia
    Karolinska Institutet.
    Granholm, Ann-Charlotte
    Medical University of South Carolina, USA.
    Mohammed, Abdul K. H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function2017In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 55, no 2, p. 645-657Article in journal (Refereed)
    Abstract [en]

    Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.

  • 14. Jacobsson, Lars
    et al.
    Ahlström, Margareta
    Stockholm university.
    Benderix, Ylva
    Linnaeus University, Faculty of Social Sciences, Department of pedagogy.
    Bergman, Bo
    Billstedt, Eva
    Davidsson, Thomas
    Ehlers, Stephan
    Grann, Martin
    Halldner-Henriksson, Linda
    Jonsson, Ulf
    Löfmark, Rurik
    Mejare, Ingegerd
    Nordin, Viviann
    Nordlund, Anders
    Starke, Mikaela
    Söderpalm, Bo
    Söderström, Margareta
    von Knorring, Anne-Liis
    Östlund, Pernilla
    Autismspektrumtillstånd: Diagnostik och insatser, vårdens organisation och patientens delaktighet. En systematisk litterturöversikt2013Report (Refereed)
  • 15.
    Johansson, Jessica
    et al.
    Örebro University.
    Landgren, Magnus
    Skaraborg Hospital.
    Fernell, Elisabeth
    Skaraborg Hospital ; Sahlgrenska Academy.
    Vumma, Ravi
    Örebro University.
    Åhlin, Arne
    Skaraborg Hospital.
    Bjerkenstedt, Lars
    Strömstad Academy.
    Venizelos, Nikolaos
    Örebro University.
    Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study2011In: Behavioral and Brain Functions, ISSN 1744-9081, E-ISSN 1744-9081, Vol. 7, no 40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The amino acid tyrosine is the precursor for synthesis of the catecholamines dopamine and norepinephrine, while tryptophan is the precursor of serotonin. A disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other psychiatric disorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim of this study was to explore whether children with ADHD may have disturbed amino acid transport.

    METHODS: Fibroblast cells were cultured from skin biopsies obtained from 14 boys diagnosed with ADHD and from 13 matching boys without a diagnosis of a developmental disorder. Transport of the amino acids tyrosine, tryptophan and alanine across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (V(max)) and affinity constant (K(m)) were determined. Any difference between the two groups was analyzed by Student's unpaired t-test or the Mann Whitney U test.

    RESULTS: The ADHD group had significantly decreased V(max) (p = 0.039) and K(m) (increased affinity) (p = 0.010) of tryptophan transport in comparison to controls. They also had a significantly higher V(max)of alanine transport (p = 0.031), but the Km of alanine transport did not differ significantly. There were no significant differences in any of the kinetic parameters regarding tyrosine transport in fibroblasts for the ADHD group.

    CONCLUSIONS: Tryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB). Hence, a decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB in the ADHD group. This could lead to deficient serotonin access in the brain that might cause disturbances in both the serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected. The physiological importance of an elevated transport capacity of alanine to the brain is not known to date.

  • 16.
    Johansson, Kjell
    et al.
    The Wallenberg Retina Center, Department of Ophthalmology, Lund University Hospital, SE-221 85 Lund, Sweden.
    Ehinger, Berndt
    The Wallenberg Retina Center, Department of Ophthalmology, Lund University Hospital, SE-221 85 Lund, Sweden.
    Postnatal development of the rat retina and some of its neurotransmitter systems in vitro.2001In: Progress in Brain Research, Vol. 131, p. 589-598Article, review/survey (Other academic)
  • 17.
    Kakooza-Mwesige, Angelina
    et al.
    Makerere Univ, Uganda;Mulago Hosp, Uganda.
    Mohammed, Abdul K. H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Kristensson, Krister
    Karolinska Institutet.
    Juliano, Sharon L.
    Uniformed Serv Univ Hlth Sci, USA.
    Lutwama, Julius J.
    Uganda Virus Res Inst, Uganda.
    Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 82Article, review/survey (Refereed)
    Abstract [en]

    The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood.

  • 18. Lagrosen, Yvonne
    et al.
    Travis, Frederick
    Lagrosen, Stefan
    Högskolan Väst, Avd för företagsekonomi.
    Brain integration as a driver for quality management success2012In: International Journal of Quality and Service Sciences, ISSN 1756-669X, E-ISSN 1756-6703, Vol. 4, no 3, p. 253-269Article in journal (Refereed)
    Abstract [en]

    In this paper research leading to quality management success is examined, elaborated, and highlighted in a new profound way by focusing on the most fundamental aspect of the human dimension, the brain. The purpose is to examine the relationship between brain functioning and quality management success. In this examination, the role of core values, profound organizational learning and values of quality management are explained.

     

    Design/methodology/approach

    The paper builds on a conceptual review of research in the areas of quality management success, values of quality management, core values and neurophysiology with focus on brain integration. 

     

    Findings

    The relation of core values with brain functioning is described based on previous research. A framework with logical steps from brain integration, via core values, quality management values and quality management practices to quality management success is developed.

     

    Research limitations/implications

    The paper adds to the understanding of the role brain integration has for success in quality management efforts. A limitation is that it only builds on previous research.

     

    Practical implications

    The findings provide a deeper understanding of quality management success and should thus be valuable for quality managers and leaders striving for excellence for their organisations.

     

    Originality/value

    The importance and crucial role of brain integration for quality management success has not been elaborated in the literature of quality management before.

     

    Keywords

    Quality management, brain integration, core values, organisational learning, quality management success, culture, quality management values, decision-making

     

     

  • 19.
    Mollick, Tanzina
    et al.
    Örebro University.
    Mohlin, Camilla
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Johansson, Kjell
    Örebro University.
    Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina2016In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1646, p. 522-534Article in journal (Refereed)
    Abstract [en]

    Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Müller cell gliosis only seemed to be alleviated in terms of reduced Müller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Müller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined.

  • 20.
    Norrby, Marlene
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Evertsson, Kim
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Fjällström, Ann-Kristin
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Svensson, Anna
    Tågerud, Sven
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Akt (protein kinase B) isoform phosphorylation and signaling downstream of mTOR (mammalian target of rapamycin) in denervated atrophic and hypertrophic mouse skeletal muscle.2012In: Journal of Molecular Signaling, ISSN 1750-2187, E-ISSN 1750-2187, Vol. 7, no June, p. Article ID: 7-Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: BACKGROUND: The present study examines the hypothesis that Akt (protein kinase B)/mTOR (mammalian target of rapamycin) signaling is increased in hypertrophic and decreased in atrophic denervated muscle. Protein expression and phosphorylation of Akt1, Akt2, glycogen synthase kinase-3beta (GSK-3beta), eukaryotic initiation factor 4E binding protein 1 (4EBP1), 70 kD ribosomal protein S6 kinase (p70S6K1) and ribosomal protein S6 (rpS6) were examined in six-days denervated mouse anterior tibial (atrophic) and hemidiaphragm (hypertrophic) muscles. RESULTS: In denervated hypertrophic muscle expression of total Akt1, Akt2, GSK-3beta, p70S6K1 and rpS6 proteins increased 2-10 fold whereas total 4EBP1 protein remained unaltered. In denervated atrophic muscle Akt1 and Akt2 total protein increased 2-16 fold. A small increase in expression of total rpS6 protein was also observed with no apparent changes in levels of total GSK-3beta, 4EBP1 or p70S6K1 proteins. The level of phosphorylated proteins increased 3-13 fold for all the proteins in hypertrophic denervated muscle. No significant changes in phosphorylated Akt1 or GSK-3beta were detected in atrophic denervated muscle. The phosphorylation levels of Akt2, 4EBP1, p70S6K1 and rpS6 were increased 2-18 fold in atrophic denervated muscle. CONCLUSIONS: The results are consistent with increased Akt/mTOR signaling in hypertrophic skeletal muscle. Decreased levels of phosphorylated Akt (S473/S474) were not observed in denervated atrophic muscle and results downstream of mTOR indicate increased protein synthesis in denervated atrophic anterior tibial muscle as well as in denervated hypertrophic hemidiaphragm muscle. Increased protein degradation, rather than decreased protein synthesis, is likely to be responsible for the loss of muscle mass in denervated atrophic muscles.

  • 21.
    Persson, M L
    et al.
    Karolinska University Hospital.
    Johansson, J
    Örebro University.
    Vumma, R
    Örebro University.
    Raita, J
    Karolinska University Hospital.
    Bjerkenstedt, L
    Linköping University.
    Wiesel, F-A
    Uppsala University.
    Venizelos, N
    Örebro University.
    Aberrant amino acid transport in fibroblasts from patients with bipolar disorder2009In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 457, no 1, p. 49-52Article in journal (Refereed)
    Abstract [en]

    Aberrant tyrosine transport is a repeated finding in fibroblasts from schizophrenic patients. The transport aberration could lead to disturbances in the dopaminergic and noradrenergic neurotransmitter systems. Tyrosine and tryptophan are the precursors of the neurotransmitters dopamine and serotonin. Disturbed dopaminergic, noradrenergic and serotoninergic systems are implicated as causes of bipolar disorder. Hence, the aim of this study was to explore whether patients with bipolar disorder have an aberrant transport of tyrosine and/or tryptophan. Fibroblast cell lines from patients with bipolar type-1 disorder (n=10) and healthy controls (n=10) were included in this study. All patients fulfilled the DSM-IV diagnostic criteria. The transport of amino acids across the cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport velocity (V(max)) and affinity constant (K(m)) were determined. A significantly lower V(max) for tyrosine (p=0.027) was found in patients with bipolar type-1 disorder in comparison to healthy controls. No significant differences in K(m) for tyrosine and in the kinetic parameters of tryptophan between patients with bipolar type-1 disorder and healthy controls were observed. The decreased tyrosine transport (low V(max)) found in this study may indicate less access of dopamine in the brain, resulting in disturbed dopaminergic and/or noradrenergic neurotransmission, that secondarily could lead to disturbances in other central neurotransmitter systems, such as the serotoninergic system. However, as sample size was small in this study and an age difference between patients and controls existed, the present findings should be considered as pilot data. Further studies with larger sample number are needed to elucidate the transport aberration and the significance of these findings.

  • 22.
    Persson, ML
    et al.
    Stockholm County Council.
    Johansson, J
    Örebro University.
    Vumma, Ravi
    Örebro University.
    Raita, J
    Stockholm County Council.
    Bjerkenstedt, L
    Linköping University.
    Wiesel, FA
    Uppsala University.
    Venizelos, N
    Örebro University.
    Aberrant amino acid transport in fibroblasts from patients with bipolar disorder2009In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 457, no 1, p. 49-52, article id 19429160Article in journal (Refereed)
    Abstract [en]

    Aberrant tyrosine transport is a repeated finding in fibroblasts from schizophrenic patients. The transport aberration could lead to disturbances in the dopaminergic and noradrenergic neurotransmitter systems. Tyrosine and tryptophan are the precursors of the neurotransmitters dopamine and serotonin. Disturbed dopaminergic, noradrenergic and serotoninergic systems are implicated as causes of bipolar disorder. Hence, the aim of this study was to explore whether patients with bipolar disorder have an aberrant transport of tyrosine and/or tryptophan. Fibroblast cell lines from patients with bipolar type-1 disorder (n=10) and healthy controls (n=10) were included in this study. All patients fulfilled the DSM-IV diagnostic criteria. The transport of amino acids across the cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport velocity (V(max)) and affinity constant (K(m)) were determined. A significantly lower V(max) for tyrosine (p=0.027) was found in patients with bipolar type-1 disorder in comparison to healthy controls. No significant differences in K(m) for tyrosine and in the kinetic parameters of tryptophan between patients with bipolar type-1 disorder and healthy controls were observed. The decreased tyrosine transport (low V(max)) found in this study may indicate less access of dopamine in the brain, resulting in disturbed dopaminergic and/or noradrenergic neurotransmission, that secondarily could lead to disturbances in other central neurotransmitter systems, such as the serotoninergic system. However, as sample size was small in this study and an age difference between patients and controls existed, the present findings should be considered as pilot data. Further studies with larger sample number are needed to elucidate the transport aberration and the significance of these findings.

  • 23.
    Prohovnik, Isak
    et al.
    University of Lund.
    Håkansson, Krister
    University of Lund.
    Risberg, Jarl
    University of Lund.
    Observations on the functional significance of regional cerebral blood flow in "resting" normal subjects.1980In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 18, no 2, p. 203-17Article in journal (Refereed)
    Abstract [en]

    Regional Cerebral Blood Flow (rCBF) of 16 cortical regions was measured bilaterally in 22 healthy adults, with 4–8 repeated measurements per individual. All measurements were done during “rest”, i.e. with minimal external stimulation, by the Xe-133 inhalation method. The data are presented to serve as normal controls for research and clinical work, but more importantly because of their significance for neuropsychological theory. Some rCBF variance is shown to be meaningfully related to handedness, habituation processes, biological rhythms and possibly to regional lateral dominance. Further data and discussion relate to the possible role of frontal lobe structures during non-task-oriented cognition. Finally, data are interpreted as showing that regional functional coupling across the midline, in this situation, is inversely related to the characteristic level-of-processing associated with each area.

  • 24.
    Ricci, S.
    et al.
    Univ Roma La Sapienza, Italy.
    Businaro, R.
    Sapienza Univ, Italy.
    Ippoliti, F.
    Univ Roma La Sapienza, Italy.
    Lo Vasco, V. R.
    Univ Roma La Sapienza, Italy.
    Massoni, F.
    Univ Roma La Sapienza, Italy.
    Onofri, E.
    Univ Roma La Sapienza, Italy.
    Troili, G. M.
    Univ Roma La Sapienza, Italy.
    Pontecorvi, V.
    Sapienza Univ, Italy.
    Morelli, M.
    Sapienza Univ, Italy.
    Ricciardi, Max Rapp
    University of Gothenburg.
    Archer, Trevor
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science. University of Gothenburg.
    Altered Cytokine and BDNF Levels in Autism Spectrum Disorder2013In: Neurotoxicity research, ISSN 1029-8428, E-ISSN 1476-3524, Vol. 24, no 4, p. 491-501Article in journal (Refereed)
    Abstract [en]

    The contribution of neuroimmune functioning and brain-derived neurotrophic factor (BDNF) to functional dysregulation in autism spectrum disorder was assessed in 29 patients under treatment in two specialized centers of Basilicata (Chiaromonte and Matera), Southern Italy, through analysis of serum levels of cytokines and BDNF. Elevated levels of the pro-inflammatory cytokine, including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were observed, regardless of age and gender. Comparisons were made with age-and gender-related healthy controls. The present findings reinforce current notions regarding immunoexcitotoxic mechanisms contributing to the pathophysiology of autistic disorder.

  • 25.
    Tusch, Erich S.
    et al.
    Harvard Med Sch, USA.
    Alperin, Brittany R.
    Oregon Hlth & Sci Univ, USA.
    Ryan, Eliza
    Harvard Med Sch, USA.
    Holcomb, Phillip J.
    Tufts Univ, USA.
    Mohammed, Abdul K. H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet.
    Daffner, Kirk R.
    Harvard Med Sch, USA.
    Changes in Neural Activity Underlying Working Memory after Computerized Cognitive Training in Older Adults2016In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, article id 255Article in journal (Refereed)
    Abstract [en]

    Computerized cognitive training (CCT) may counter the impact of aging on cognition, but both the efficacy and neurocognitive mechanisms underlying CCT remain controversial. In this study, 35 older individuals were randomly assigned to Cogmed adaptive working memory (WM) CCT or an active control CCT, featuring five weeks of five similar to 40 min sessions per week. Before and after the 5-week intervention, event-related potentials were measured while subjects completed a visual n-back task with three levels of demand (0-back, 1-back, 2-back). The anterior P3a served as an index of directing attention and the posterior P3b as an index of categorizationNVM updating. We hypothesized that adaptive CCT would be associated with decreased P3 amplitude at low WM demand and increased P3 amplitude at high WM demand. The adaptive CCT group exhibited a training-related increase in the amplitude of the anterior P3a and posterior P3b in response to target stimuli across n-back tasks, while subjects in the active control CCT group demonstrated a post-training decrease in the anterior P3a. Performance did not differ between groups or sessions. Larger overall P3 amplitudes were strongly associated with better task performance. Increased post-CCT P3 amplitude correlated with improved task performance; this relationship was especially robust at high task load. Our findings suggest that adaptive WM training was associated with increased orienting of attention, as indexed by the P3a, and the enhancement of categorization/WM updating processes, as indexed by the P3b. Increased P3 amplitude was linked to improved performance; however. there was no direct association between adaptive training and improved performance.

  • 26.
    Vumma, Ravi
    et al.
    Örebro University.
    Johansson, Jessica
    Örebro University.
    Lewander, Tommy
    Uppsala University Hospital.
    Venizelos, Nikolaos
    Örebro University.
    Tryptophan transport in human fibroblast cells-a functional characterization.2011In: International Journal of Tryptophan Research, ISSN 1178-6469, Vol. 4, p. 19-27Article in journal (Refereed)
    Abstract [en]

    There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to identify the main transporters of tryptophan in fibroblast cell lines from healthy controls.Tryptophan kinetic parameters (V(max) and K(m)) at low and high concentrations were measured in fibroblasts using the cluster tray method. Uptake of (3)H (5)-L-tryptophan at different concentrations in the presence and absence of excess concentrations of inhibitors or combinations of inhibitors of amino acid transporters were also measured. Tryptophan transport at high concentration (0.5 mM) had low affinity and high V(max) and the LAT1 isoform of system-L was responsible for approximately 40% of the total uptake of tryptophan. In comparison, tryptophan transport at low concentration (50 nM) had higher affinity, lower V(max) and approximately 80% of tryptophan uptake was transported by system-L with LAT1 as the major isoform. The uptake of tryptophan at the low concentration was mainly sodium (Na(+)) dependent, while uptake at high substrate concentration was mainly Na(+) independent. A series of different transporter inhibitors had varying inhibitory effects on tryptophan uptake.This study indicates that tryptophan is transported by multiple transporters that are active at different substrate concentrations in human fibroblast cells. The tryptophan transport trough system-L was mainly facilitated by the LAT1 isoform, at both low and high substrate concentrations of tryptophan.

  • 27.
    Vumma, Ravi
    et al.
    Örebro University.
    Wiesel, Frits-Axel
    Uppsala University Hospital.
    Flyckt, Lena
    Danderyd's Hospital.
    Bjerkenstedt, Lars
    Linköping University.
    Venizelos, Nikolaos
    Örebro University.
    Functional characterization of tyrosine transport in fibroblast cells from healthy controls2008In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 434, no 1, p. 56-60Article in journal (Refereed)
    Abstract [en]

    Human fibroblast cells are an advantageous model to study the transport of amino acids across cell membranes, since one can control the environmental factors. A major problem in all earlier studies is the lack of precise and detailed knowledge regarding the expression and functionality of tyrosine transporters in human fibroblasts. This motivated us to perform a systematic functional characterization of the tyrosine transport in fibroblast cells with respect to the isoforms of system-L (LAT1, LAT2, LAT3, LAT4), which is the major transporter of tyrosine. Ten (n=10) fibroblast cell lines from healthy volunteers were included in the study. Uptake of L-[U-14C] tyrosine in fibroblasts was measured using the cluster tray method in the presence and absence of excess concentrations of various combinations of inhibitors. This study demonstrated that LAT1 is involved in 90% of total uptake of tyrosine and also around 51% of alanine. Not more than 10% can be accounted for by LAT2, LAT3 and LAT4 isoforms. LAT2 seems to be functionally weak in uptake of tyrosine while LAT3 and LAT4 contributed around 7%. 10% could be contributed by system-A (ATA2 isoform). Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine transport through the LAT1 isoform has a higher affinity compared to system-L. In conclusion, the LAT1 isoform is the major transporter of tyrosine in human fibroblast cells. Competition between tyrosine and alanine for transport is shown to exist, probably between LAT1 and LAT2 isoforms. This study established fibroblast cells as a suitable experimental model for studying amino acid transport defects in humans.

  • 28.
    Wadenberg, Marie-Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Manetti, Dina
    Univ Florence, Italy.
    Romanelli, Maria Novella
    Univ Florence, Italy.
    Arias, Hugo R.
    Calif Northstate Univ, USA.
    Significance of the nicotinic alpha7 receptor in cognition and antipsychotic-like behavior in the rat2017In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 333, p. 129-134Article in journal (Refereed)
    Abstract [en]

    Schizophrenic (SCH) patients show cognitive impairment in attentional performance. Positive allosteric modulators (PAMs) of alpha 7 nicotinic acetylcholine receptors (nAChRs) such as the Alzheimer's drug galantamine (GAL) and PAM-2 are documented to have pro-cognitive properties. However, it is not well established if these properties would be lost, or may hamper antipsychotic efficacy, when given as an adjunct to an antipsychotic which is needed for managing psychotic symptoms. Using adult male Wistar rats, we here investigated the effects of: a) GAL, alone or co-administered with the antipsychotic risperidone (RISP), on acute phencyclidine (PCP) induced deficits in the attentional set-shifting (ASST) test; b) PAM-2, alone and co-administered with RISP, in the conditioned avoidance response (CAR) test for antipsychotic activity. Acute PCP produced selective and significant SCH-like impairment in extra dimensional shift (EDS) performance, which was completely reversed by GAL. The ability of GAL to reverse PCP-induced EDS impairment was not prevented when co-administered with RISP, suggesting that the combination of GAL and low doses of RISP may be used to improve the cognitive impairment in SCH. Pretreatment with methyllycaconitine (MLA), a selective alpha 7 nAChR antagonist, completely prevented the reversal elicited by GAL, supporting the concept that alpha 7 nAChRs are involved in this process. On the other hand, PAM-2 alone had no effects on CAR, but enhanced, although not significantly, the antipsychotic-like effect of RISP when administered together. In conclusion, alpha 7 PAMs, in addition to alleviate the cognitive impairments observed in SCH patients, may enhance the anti psychotic efficacy of atypical antipsychotics.

  • 29.
    Waxegård, Gustaf
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Thulesius, Hans
    Region Kronoberg, Sweden;Lund University, Sweden.
    Integrating care for neurodevelopmental disorders by unpacking control: A grounded theory study2016In: International Journal of Qualitative Studies on Health and Well-being, ISSN 1748-2623, E-ISSN 1748-2631, Vol. 11, article id 31987Article in journal (Refereed)
    Abstract [en]

    Background: To establish integrated healthcare pathways for patients with neurodevelopmental disorders ( ND) such as autism spectrum disorder and attention-deficit hyperactivity disorder is challenging. This study sets out to investigate the main concerns for healthcare professionals when integrating ND care pathways and how they resolve these concerns. Methods: Using classic grounded theory ( Glaser), we analysed efforts to improve and integrate an ND care pathway for children and youth in a Swedish region over a period of 6 years. Data from 42 individual interviews with a range of ND professionals, nine group interviews with healthcare teams, participant observation, a 2-day dialogue conference, focus group meetings, regional media coverage, and reports from other Swedish regional ND projects were analysed. Results: The main concern for participants was to deal with overwhelming ND complexity by unpacking control, which is control over strategies to define patients' status and needs. Unpacking control is key to the professionals' strivings to expand constructive life space for patients, to squeeze health care to reach available care goals, to promote professional ideologies, and to uphold workplace integrity. Control-seeking behaviour in relation to ND unpacking is ubiquitous and complicates integration of ND care pathways. Conclusions: The Unpacking control theory expands central aspects of professions theory and may help to improve ND care development.

  • 30.
    Williams, Donald
    et al.
    University of California, USA.
    Carlsson, Rickard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Bürkner, Paul-Christian
    University of Münster, Germany.
    Between-litter variation in developmental studies of hormones and behavior: Inflated false positives and diminished power2017In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 47, p. 154-166Article in journal (Refereed)
    Abstract [en]

    Developmental studies of hormones and behavior often include littermates—rodent siblings that share early-life experiences and genes. Due to between-litter variation (i.e., litter effects), the statistical assumption of independent observations is untenable. In two literatures—natural variation in maternal care and prenatal stress—entire litters are categorized based on maternal behavior or experimental condition. Here, we (1) review both literatures; (2) simulate false positive rates for commonly used statistical methods in each literature; and (3) characterize small sample performance of multilevel models (MLM) and generalized estimating equations (GEE). We found that the assumption of independence was routinely violated (>85%), false positives (α = 0.05) exceeded nominal levels (up to 0.70), and power (1−β) rarely surpassed 0.80 (even for optimistic sample and effect sizes). Additionally, we show that MLMs and GEEs have adequate performance for common research designs. We discuss implications for the extant literature, the field of behavioral neuroendocrinology, and provide recommendations.

  • 31.
    Yang, Lin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Role of butyrate in counteracting the influence of oxidative stress on amino acid transport implicated in neuropsychiatric disorders2018Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
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