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Article Dans Une Revue Neurobiology of Aging Année : 2016

A role for b2* nicotinic receptors in a model of local amyloid pathology induced in dentate gyrus

Résumé

Keywords: In vivo amyloid pathology Amyloid precursor protein a7 nicotinic receptor b2 nicotinic receptor Memory deficit Hippocampus a b s t r a c t 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 (Ab), and associated memory impairment. We then investigated the role of a7 or b2 subunits of the nicotinic acetylcholine receptor by transducing hAPP-SLA into C57Bl/ 6J mice knockout (KO) for a7 or b2 subunits. b2 KO mice did not exhibit memory loss induced by hAPP-SLA expression, whereas aged mice lacking the a7 subunit displayed a hAPP-SLA independent cognitive deficit. The present data reveal a role for b2 containing nicotinic acetylcholine receptors in the memory deficits associated with DG specific amyloid beta expression.
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hal-01573489 , version 1 (10-08-2017)

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Sylvia Lombardo, Julie Catteau, Morgane Besson, Uwe Maskos. A role for b2* nicotinic receptors in a model of local amyloid pathology induced in dentate gyrus. Neurobiology of Aging, 2016, 46, pp.221-234. ⟨10.1016/j.neurobiolaging.2016.06.005⟩. ⟨hal-01573489⟩
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