HSV-1 promotes Ca2+-mediated APP phosphorylation and Aβ accumulation in rat cortical neurons

Roberto Piacentini, Livia Civitelli, Cristian Ripoli, Maria Elena Marcocci, Giovanna De Chiara, Enrico Garaci, Gian Battista Azzena, Anna Teresa Palamara, Claudio Grassi

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75 Citations (Scopus)


Epidemiological and experimental findings suggest that chronic infection with herpes simplex virus type 1 (HSV-1) may be a risk factor for Alzheimer’s disease (AD), but the molecular mechanisms underlying this association have not been fully identified. We investigated the effects of HSV-1 on excitability and intracellular calcium signaling in rat cortical neurons and the impact of these effects on amyloid precursor protein (APP) processing and the production of amyloid-β peptide (Aβ). Membrane depolarization triggering firing rate increases was observed shortly after neurons were challenged with HSV-1 and was still evident 12 hours postinfection. These effects depended on persistent sodium current activation and potassium current inhibition. The virally induced hyperexcitability triggered intracellular Ca2+ signals that significantly increased intraneuronal Ca2+ levels. It also enhanced activity- and Ca2+-dependent APP phosphorylation and intracellular accumulation of Aβ42. These findings indicate that HSV-1 causes functional changes in cortical neurons that promote APP processing and Aβ production, and they are compatible with the co-factorial role for HSV-1 in the pathogenesis of AD suggested by previous findings.
Original languageEnglish
Pages (from-to)2323.e13-2323.e26
Number of pages14
JournalNeurobiology of Aging
Publication statusPublished - 2011


  • Amyloid Beta Protein
  • Herpes Simplex Type-1


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