Amyloid β-Induced Upregulation of Na_v1.6 Underlies Neuronal Hyperactivity in Tg2576 Alzheimer's Disease Mouse Model.

ABSTRACT: Hyperexcitability and alterations in neuronal networks contribute to cognitive impairment in Alzheimer's Disease (AD). Voltage-gated sodium channels (Na_V), which are crucial for regulating neuronal excitability, have been implicated in AD-related hippocampal hyperactivity and higher incidence of spontaneous non-convulsive seizures. Here, we show by using primary hippocampal neurons exposed to amyloid-β_1-42 (Aβ_1-42) oligomers and from Tg2576 mouse embryos, that the selective upregulation of Na_V1.6 subtype contributes to membrane depolarization and to the increase of spike frequency, thereby resulting in neuronal hyperexcitability. Interestingly, we also found that Na_V1.6 overexpression is responsible for the aberrant neuronal activity o

SUBMITTER: Ciccone R 

PROVIDER: S-EPMC6753212 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature