A role for β2*nicotinic receptors in a model of local amyloid pathology induced in dentate gyrus

NEUROBIOLOGY OF AGING

卷:46

Article

Lombardo, Sylvia^1,2,3  Catteau, Julie^1,2  Besson, Morgane^1,2  Maskos, Uwe^1,2 

[1] Inst Pasteur, Dept Neurosci, Unite Neurobiol Integrat Syst Cholinerg, Paris, France

[2] CNRS, UMR 3571, Paris, France

[3] Tufts Univ, Sch Med, Dept Neurosci, Alzheimers Dis Res Lab, Boston, MA 02111 USA

关键词: In vivo amyloid pathology;    Amyloid precursor protein;    alpha 7 nicotinic receptor;    beta 2 nicotinic receptor;    Memory deficit;    Hippocampus;   

DOI  :  10.1016/j.neurobiolaging.2016.06.005

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD) is characterized by the presence of plaques and tangles. Only certain brain regions are vulnerable to progressive neurodegeneration. It is therefore important to study the contribution of key brain structures to AD pathology. Here, we investigated the consequences of amyloid accumulation specifically in dentate gyrus (DG). This was obtained with viral transduction of human amyloid precursor protein harboring 3 pathogenic mutations (hAPP-SLA, Swedish, London, and Austrian) in DG. Adult wild-type C57Bl/6J mice exhibited long-term expression of hAPP-SLA, synthesis and deposition of oligomeric amyloid beta (A beta), and associated memory impairment. We then investigated the role of alpha 7 or beta 2 subunits of the nicotinic acetylcholine receptor by transducing hAPP-SLA into C57Bl/6J mice knock-out (KO) for alpha 7 or beta 2 subunits. beta 2 KO mice did not exhibit memory loss induced by hAPP-SLA expression, whereas aged mice lacking the alpha 7 subunit displayed a hAPP-SLA independent cognitive deficit. The present data reveal a role for beta 2 containing nicotinic acetylcholine receptors in the memory deficits associated with DG specific amyloid beta expression. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

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