Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis

Silvia Rossi, Valentina De Chiara, Alessandra Musella, Mauro Cozzolino, Giorgio Bernardi, Mauro MacCarrone, Nicola B. Mercuri, Maria Teresa Carrí, Diego Centonze

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons. However, additional neuronal systems are also involved, and the aim of this study was to investigate the involvement of the nucleus striatum. By means of neurophysiological recordings in slices, we have investigated both excitatory and inhibitory synaptic transmission in the striatum of G93A-SOD1 ALS mice, along with the sensitivity of these synapses to cannabinoid CB1 receptor stimulation. We have observed reduced frequency of glutamate-mediated spontaneous excitatory postsynaptic currents (EPSCs) and increased frequency of GABA-mediated spontaneous inhibitory postsynaptic currents (IPSCs) recorded from striatal neurons of ALS mice, possibly due to presynaptic defects in transmitter release. The sensitivity of cannabinoid CB1 receptors controlling both glutamate and GABA transmission was remarkably potentiated in ALS mice, indicating that adaptations of the endocannabinoid system might be involved in the pathophysiology of ALS. In conclusion, our data identify possible physiological correlates of striatal dysfunction in ALS mice, and suggest that cannabinoid CB1 receptors might be potential therapeutic targets for this dramatic disease.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalAmyotrophic Lateral Sclerosis
Volume11
Issue number1-2
DOIs
Publication statusPublished - 2010

Keywords

  • ALS
  • CB1 receptors
  • Endocannabinoids
  • EPSC
  • IPSC

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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