title: A role for β2* nicotinic receptors in a model of local amyloid pathology induced in dentate gyrus.
abstract: 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 (Aβ), and associated memory impairment. We then investigated the role of α7 or β2 subunits of the nicotinic acetylcholine receptor by transducing hAPP-SLA into C57Bl/6J mice knock-out (KO) for α7 or β2 subunits. β2 KO mice did not exhibit memory loss induced by hAPP-SLA expression, whereas aged mice lacking the α7 subunit displayed a hAPP-SLA independent cognitive deficit. The present data reveal a role for β2 containing nicotinic acetylcholine receptors in the memory deficits associated with DG specific amyloid beta expression.
authors: Institut Pasteur, Département de Neuroscience, Unité Neurobiologie intégrative des systèmes cholinergiques, Paris, France; CNRS, UMR 3571, Paris, France.
authors: Sylvia
authors: S
authors: Lombardo
authors: Institut Pasteur, Département de Neuroscience, Unité Neurobiologie intégrative des systèmes cholinergiques, Paris, France; CNRS, UMR 3571, Paris, France.
authors: Julie
authors: J
authors: Catteau
authors: Institut Pasteur, Département de Neuroscience, Unité Neurobiologie intégrative des systèmes cholinergiques, Paris, France; CNRS, UMR 3571, Paris, France.
authors: Morgane
authors: M
authors: Besson
authors: Institut Pasteur, Département de Neuroscience, Unité Neurobiologie intégrative des systèmes cholinergiques, Paris, France; CNRS, UMR 3571, Paris, France. Electronic address: umaskos@pasteur.fr.
authors: Uwe
authors: U
authors: Maskos
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D011978:Receptors, Nicotinic
keywords: Amyloid precursor protein; Hippocampus; In vivo amyloid pathology; Memory deficit; α7 nicotinic receptor; β2 nicotinic receptor