Herpes Simplex Virus type 1 (HSV-1) increases the excitability of rat neocortical neurons and triggers amyloid precursor protein (APP) processing.

Roberto Piacentini, Cristian Ripoli, Livia Civitelli, Maria Elena Marcocci, Giovanna De Chiara, Anna Teresa Palamara, Claudio Grassi

Risultato della ricerca: Contributo in rivistaContributo a convegno


Introduction: HSV-1 infection may spread within the central nervous system and cause neurological disorders including encephalitis and epileptic seizures. Recurrent HSV-1 infections have also been proposed to play a co-factorial role in the pathogenesis of Alzheimer’s disease. Objective: Aim of our study was to determine the effects of HSV-1 on electrophysiological properties of cortical neurons, and the pathophysiological impact of virally induced changes. Methods: Patch-clamp, immunofluorescence and Western blot experiments were performed on rat cultured cortical neurons either soon after challenge with HSV-1 or 12 24 hours post-infection (hpi). Results: Cell exposure to HSV-1 induced membrane depolarization (11.8±0.7 mV) that triggered action potentials and increased the discharge rate of spontaneously firing neurons (from 0.1±0.1 to 1.1±0.3 Hz). This effect depended on viral binding to neuronal membrane. In fact, when cells were challenged with HSV-1 pretreated with heparin (which prevents the binding of viral glicoproteins to membrane receptors) no depolarization was observed whereas when we applied UV-inactivated HSV-1 (that binds to membrane but is unable to replicate) the observed responses were similar to those produced by active virus. In most neurons, membrane depolarization started soon after HSV-1 application and steady-state was reached after 2 10 s. This effect was due to both inhibition of leak K+ currents and increase of persistent Na+ currents (+53% at 20 mV). Neither transient Na+ currents nor Ca2+ currents were affected. Similar effects were observed 12 hpi. The HSV-1-induced neuronal hyperexcitability triggered intracellular Ca2+ signals promoting APP processing and intracellular and extracellular accumulation of amyloid-b peptide and several neurotoxic APP fragments. Conclusions: Changes in neuronal electrophysiological properties induced by HSV-1 may play a role in the pathophysiology of epileptic seizures and neurodegeneration.
Lingua originaleEnglish
pagine (da-a)S106-S106
Numero di pagine1
RivistaClinical Neurophysiology
Stato di pubblicazionePubblicato - 2011
Evento14th European Congress on Clinical Neurophysiology - Roma
Durata: 21 giu 201124 giu 2011


  • Amyloid precursor protein
  • Amyloid-beta protein
  • Calcium signals
  • Cav1 channels
  • HSV-1
  • Persistent Na+ currents


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