Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-β protein accumulation.

ABSTRACT: Increasing evidence suggests that recurrent Herpes Simplex Virus type 1 (HSV-1) infection spreading to the CNS is a risk factor for Alzheimer's Disease (AD) but the underlying mechanisms have not been fully elucidated yet. Here we demonstrate that in cultured mouse cortical neurons HSV-1 induced Ca(2+)-dependent activation of glycogen synthase kinase (GSK)-3. This event was critical for the HSV-1-dependent phosphorylation of amyloid precursor protein (APP) at Thr668 and the following intraneuronal accumulation of amyloid-β protein (Aβ). HSV-1-infected neurons also exhibited: i) significantly reduced expression of the presynaptic proteins synapsin-1 and synaptophysin; ii) depressed synaptic transmission. These effects depended on GSK-3 activation and intraneuronal accumulation of Aβ. In fac

SUBMITTER: Piacentini R 

PROVIDER: S-EPMC4614347 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature