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

Department of Neuroscience, Maastricht University, 6200 MD, Maastricht, The Netherlands.
Brain Structure and Function (Impact Factor: 4.57). 03/2010; 214(2-3):145-60. DOI: 10.1007/s00429-010-0242-4
Source: PubMed

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.

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Available from: Daniel P Perl, Aug 23, 2015
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    • "). Marked loss in CR-IR cells was previously reported in the hippocampus of mice with experimental AD and in human patients (Takahashi et al., 2010). Our results demonstrate a significant age-dependent vulnerability of CR + cells in the SGZ, a site of adult neurogenesis. "
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    • "PV is an essential element of learning networks. The decrease in their cell number occurs in some cases of epilepsy (Castro et al., 2011; Dinocourt et al., 2003), Alzheimer's disease (Brady and Mufson, 1997; Takahashi et al., 2010), schizophrenia (Nullmeier et al., 2011; Zhang and Reynolds, 2002), and other disorders such as dementia with Lewis bodies (Bernstein et al., 2011). Although the rhythmicity Fig. 4 – Distributions of CB-IR, CR-IR and PV-IR neurons in the polymorphic layer of the dentate gyrus of the primate Sapajus apella. "
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    • "The model we used mimics many features of AD, including robust neuroinflammation, synaptic damage and neuronal loss in the hippocampus as has also been shown in our institution. The loss of CR neurons that has been recently reported (Baglietto-Vargas et al., 2010; Stepanichev et al., 2006; Takahashi et al., 2010) refers to a different experimental condition, where PS1/AbetaPP transgenic mice were used and the observations were carried out on 2–12 month old mice. However, even if the differences could be species-specific, we agree with these authors that CR-containing hippocampal neurons are early targets of βA pathology, induced in our study by central administration. "
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