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Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer's disease

Takahashi, Hisaaki
Brasnjevic, Ivona
Rutten, Bart P. F.
Van Der Kolk, Nicolien
Perl, Daniel P.
Steinbusch, Harry W. M.
Schmitz, Christoph
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Published in Brain Structure and Function. 2010, vol. 214, no. 2-3, p. 145-160
Abstract Hippocampal atrophy and neuron loss are commonly found in Alzheimer's disease (AD). However, the underlying molecular mechanisms and the fate in the AD hippocampus of subpopulations of interneurons that express the calcium-binding proteins parvalbumin (PV) and calretinin (CR) has not yet been properly assessed. Using quantitative stereologic methods, we analyzed the regional pattern of age-related loss of PV- and CR-immunoreactive (ir) neurons in the hippocampus of mice that carry M233T/L235P knocked-in mutations in presenilin-1 (PS1) and overexpress a mutated human beta-amyloid precursor protein (APP), namely, the APP(SL)/PS1 KI mice, as well as in APP(SL) mice and PS1 KI mice. We found a loss of PV-ir neurons (40-50%) in the CA1-2, and a loss of CR-ir neurons (37-52%) in the dentate gyrus and hilus of APP(SL)/PS1 KI mice. Interestingly, comparable PV- and CR-ir neuron losses were observed in the dentate gyrus of postmortem brain specimens obtained from patients with AD. The loss of these interneurons in AD may have substantial functional repercussions on local inhibitory processes in the hippocampus.
Keywords AgedAged, 80 and overAlzheimer Disease/*genetics/*pathology/physiopathologyAmyloid beta-Protein Precursor/geneticsAnimalsBiological Markers/metabolismCalcium-Binding Protein, Vitamin D-Dependent/metabolismCell CountDentate Gyrus/metabolism/pathology/physiopathologyFemaleGene Knock-In TechniquesHippocampus/metabolism/*pathology/physiopathologyHumansInterneurons/metabolism/*pathologyMaleMiceNerve Degeneration/*genetics/metabolism/physiopathologyNeural Inhibition/geneticsParvalbumins/metabolismPresenilin-1/genetics
PMID: 20213270
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Research group Groupe Bouras Constantin (neuropsychiatrie) (1)
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TAKAHASHI, Hisaaki et al. Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer's disease. In: Brain Structure and Function, 2010, vol. 214, n° 2-3, p. 145-160. https://archive-ouverte.unige.ch/unige:21331

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Deposited on : 2012-05-23

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