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

Roberto Piacentini, Domenica Donatella Li Puma, Cristian Ripoli, Claudio Grassi, Maria Elena Marcocci, Giovanna De Chiara, Enrico Garaci, Anna Teresa Palamara

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

57 Citazioni (Scopus)

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 fact, either the selective GSK-3 inhibitor, SB216763, or a specific antibody recognizing Aβ (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 Aβ 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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine14
RivistaScientific Reports
Volume2015
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • AMYLOID-BETA
  • HERPES
  • Herpes simplex virus type 1
  • NEURONS

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