| First Author | Piacentini R | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 15444 | PubMed ID | 26487282 |
| Mgi Jnum | J:336369 | Mgi Id | MGI:6216004 |
| Doi | 10.1038/srep15444 | Citation | Piacentini R, et al. (2015) Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-beta protein accumulation. Sci Rep 5:15444 |
| abstractText | 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-beta protein (Abeta). 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 Abeta. In fact, either the selective GSK-3 inhibitor, SB216763, or a specific antibody recognizing Abeta (4G8) significantly counteracted the effects induced by HSV-1 at the synaptic level. Moreover, in neurons derived from APP KO mice and infected with HSV-1 Abeta accumulation was not found and synaptic protein expression was only slightly reduced when compared to wild-type infected neurons. These data further support our contention that HSV-1 infections spreading to the CNS may contribute to AD phenotype. |
