Maladaptive exploratory behavior and neuropathology of the PS-1 P117L Alzheimer transgenic mice

Article Article scientifique Rapport de cas Maladaptive exploratory behavior and neuropathology of the PS-1 P117L Alzheimer transgenic mice eng 2013 author Zufferey Valérie 652934 author Vallet Philippe 526543 author Moeri Michael 632971 author Moulin-Sallanon Marcelle author Piotton Françoise 22090 author Marin Pascale 22116 author Savioz Armand 0000-0001-8059-8281 135243 17-22 10.1016/j.brainresbull.2013.01.011 23396115 0361-9230 Patients with the early-onset Alzheimer's disease P117L mutation in the presenilin-1 gene (PS-1) present pathological hallmarks in the hippocampus, the frontal cortex and the basal ganglia. In the present work we determined by immunohistochemistry which brain regions were injured in the transgenic PS-1 P117L mice, in comparison to their littermates, the B6D2 mice. Furthermore, as these regions are involved in novelty detection, we investigated the behavior of these mice in tests for object and place novelty recognition. Limited numbers of senile plaques and neurofibrillary tangles were detected in aged PS-1 P117L mice in the CA1 only, indicating that the disease is restrained to an initial neuropathological stage. Western blots showed a change in PSD-95 expression (p=0.03), not in NR2A subunit, NR2B subunit and synaptophysin expressions in the frontal cortex, suggesting specific synaptic alterations. The behavioral tests repeatedly revealed, despite a non-significant preference for object or place novelty, maladaptive exploratory behavior of the PS-1 P117L mice in novel environmental conditions, not due to locomotor problems. These mice, unlike the B6D2 mice, were less inhibited to visit the center of the cages (p=0.01) and they continued to move excessively in the presence of a displaced object (p=0.021). Overall, the PS-1 P117L mice appear to be in an initial Alzheimer's disease-like neuropathological stage, and they showed a lack of reaction toward novel environmental conditions. Dewey 590 Dewey 616.89 44 Département de génétique et évolution 162 60 Département de psychiatrie 225 false 1 Groupe Bouras Constantin (neuropsychiatrie) 1 Brain research bulletin 94 5ca3a0cb-08e1-49d1-b275-2bbee4a3abb6 Article (Published version) Restricted 1-s2.0-S0361923013000129-main.pdf 589039 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Maladaptive exploratory behavior and neuropathology of the PS-1 P117L Alzheimer transgenic mice	Brain research bulletin			2013	623	2

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Moeri, Michael