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  • 1. Codita, Alina
    et al.
    Gumucio, Astrid
    Lannfelt, Lars
    Gellerfors, Pär
    Winblad, Bengt
    Mohammed, Abdul K. H.
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Education, Psychology and Sport Science. Karolinska institutet.
    Nilsson, Lars N G
    Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study.2010In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 215, no 1, p. 83-94Article in journal (Refereed)
    Abstract [en]

    Transgenic animals expressing mutant human amyloid precursor protein (APP) are used as models for Alzheimer disease (AD). Ideally, behavioral tests improve the predictive validity of studies on animals by mirroring the functional impact of AD-like neuropathology. Learning and memory studies in APP transgenic models have been difficult to replicate. Standardization of procedures, automatization or improved protocol design can improve reproducibility. Here the IntelliCage, an automated system, was used for behavioral testing of APP female transgenic mice with both the Arctic and Swedish mutations, the tg-ArcSwe model. Protocols covering exploration, operant learning, place learning and extinction of place preference as well as passive avoidance tests were used for longitudinal characterization of behavior. Differences in exploratory activity were significant at four months of age, when plaque-free tg-ArcSwe mice visited less frequently the IntelliCage corners and initially performed fewer visits with licks compared to non-tg animals, inside the new environment. Fourteen months old tg-ArcSwe mice required a longer time to re-habituate to the IntelliCages than non-tg mice. At both ages tg-ArcSwe mice perseverated in place preference extinction test. Fourteen months old tg-ArcSwe mice were impaired in hippocampus-dependent spatial passive avoidance learning. This deficit was found to inversely correlate to calbindin-D28k immunoreactivity in the polymorphic layer of the dentate gyrus. Reduced water intake and body weight were observed in 4 months old tg-ArcSwe animals. The body weight difference increased with age. Thus behavioral and metabolic changes in the tg-ArcSwe APP model were detected using the IntelliCage, a system which provides the opportunity for standardized automated longitudinal behavioral phenotyping.

  • 2.
    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.

  • 3. Zhu, Shun-Wei
    et al.
    Codita, Alina
    Bogdanovic, Nenad
    Hjerling-Leffler, Jens
    Ernfors, Patrik
    Winblad, Bengt
    Dickins, David W.
    Mohammed, Abdul K. H.
    Växjö University, Faculty of Humanities and Social Sciences, School of Social Sciences. Alzheimer's Disease Research Center, NVS Department, Karolinska Institutet, Stockholm 141 86, Sweden.
    Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice2009In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 197, no 2, p. 339-346Article in journal (Refereed)
    Abstract [en]

    It is widely accepted that brain derived neurotrophic factor (BDNF) plays a crucial role in mediating changes in learning and memory performance induced by environmental conditions. In order to ascertain whether BDNF modulates environmentally induced changes in exploratory behaviour, we examined mice carrying a deletion in one copy of the BDNF gene. Young heterozygous male BDNF knockout mice (BDNF+/−) and their wild-type (WT) controls were exposed to the enriched environment condition (EC) or the standard condition (SC) for 8 weeks. Exploratory behaviour was assessed in the open-field (OF) and hole-board (HB) test. Brains from EC and SC reared animals were processed for Golgi-Cox staining and the dendritic spine density in the dentate gyrus (DG) and CA1 hippocampal regions were examined. We found behavioural differences both due to the genetic modification and the environmental manipulation, with the BDNF+/− mice being more active in the OF whereas the EC mice had increased exploratory behaviour in the HB test. Environmental enrichment also led to an increase in dendritic spines in the hippocampal CA1 region and DG of the wild-type mice. This effect was also found in the enriched BDNF+/− mice, but was less pronounced. Our findings support the critical role of BDNF in behavioural and neural plasticity associated with environmental enrichment and suggest that besides maze learning performance, BDNF dependent mechanisms are also involved in other aspects of behaviour. Here we provide additional evidence that exploratory activity is influenced by BDNF.

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