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Modified age-dependent expression of NaV1.6 in an ALS model correlates with motor cortex excitability alterations.
Saba, Luana; Viscomi, Maria Teresa; Martini, Alessandro; Caioli, Silvia; Mercuri, Nicola Biagio; Guatteo, Ezia; Zona, Cristina.
Afiliação
  • Saba L; Department of Systems Medicine, University of Rome "Tor Vergata" via Montpellier 1, Rome 00133, Italy.
  • Viscomi MT; Università Cattolica del Sacro Cuore, Istituto di Istologia ed Embriologia, Fondazione Policlinico Universitario A. Gemelli, Largo F. Vito 1, Rome 00168, Italy.
  • Martini A; IRCCS Fondazione Santa Lucia, via del Fosso di Fiorano 64, Rome 00143, Italy.
  • Caioli S; IRCCS Fondazione Santa Lucia, via del Fosso di Fiorano 64, Rome 00143, Italy.
  • Mercuri NB; Department of Systems Medicine, University of Rome "Tor Vergata" via Montpellier 1, Rome 00133, Italy; IRCCS Fondazione Santa Lucia, via del Fosso di Fiorano 64, Rome 00143, Italy.
  • Guatteo E; IRCCS Fondazione Santa Lucia, via del Fosso di Fiorano 64, Rome 00143, Italy; Department of Motor Science and Wellness, University of Naples 'Parthenope', Via Medina 40, Naples 80133, Italy.
  • Zona C; Department of Systems Medicine, University of Rome "Tor Vergata" via Montpellier 1, Rome 00133, Italy; IRCCS Fondazione Santa Lucia, via del Fosso di Fiorano 64, Rome 00143, Italy. Electronic address: zona@uniroma2.it.
Neurobiol Dis ; 130: 104532, 2019 10.
Article em En | MEDLINE | ID: mdl-31302244
Cortical hyperexcitability is an early and intrinsic feature of Amyotrophic Lateral Sclerosis (ALS), but the mechanisms underlying this critical neuronal dysfunction are poorly understood. Recently, we have demonstrated that layer V pyramidal neurons (PNs) in the primary motor cortex (M1) of one-month old (P30) G93A ALS mice display an early hyperexcitability status compared to Control mice. In order to investigate the time-dependent evolution of the cortical excitability in the G93A ALS model, here we have performed an electrophysiological and immunohistochemical study at three different mouse ages. M1 PNs from 14-days old (P14) G93A mice have shown no excitability alterations, while M1 PNs from 3-months old (P90) G93A mice have shown a hypoexcitability status, compared to Control mice. These age-dependent cortical excitability dysfunctions correlate with a similar time-dependent trend of the persistent sodium current (INaP) amplitude alterations, suggesting that INaP may play a crucial role in the G93A cortical excitability aberrations. Specifically, immunohistochemistry experiments have indicated that the expression level of the NaV1.6 channel, one of the voltage-gated Na+ channels mainly distributed within the central nervous system, varies in G93A primary motor cortex during disease progression, according to the excitability and INaP alterations, but not in other cortical areas. Microfluorometry experiments, combined with electrophysiological recordings, have verified that P30 G93A PNs hyperexcitability is associated to a greater accumulation of intracellular calcium ([Ca2+]i) compared to Control PNs, and that this difference is still present when G93A and Control PNs fire action potentials at the same frequency. These results suggest that [Ca2+]i de-regulation in G93A PNs may contribute to neuronal demise and that the NaV1.6 channels could be a potential therapeutic target to ameliorate ALS disease progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canal de Sódio Disparado por Voltagem NAV1.6 / Esclerose Lateral Amiotrófica / Córtex Motor / Neurônios Motores Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canal de Sódio Disparado por Voltagem NAV1.6 / Esclerose Lateral Amiotrófica / Córtex Motor / Neurônios Motores Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article