title: Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis.
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.
authors.affiliation: Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.forename: Valentina
authors.initials: V
authors.lastname: De Chiara
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.forename: Mauro
authors.initials: M
authors.lastname: Cozzolino
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Mercuri
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Carrì
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D003342:Corpus Striatum / Q000503:physiopathology; D004195:Disease Models, Animal; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009410:Nerve Degeneration / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D013759:Dronabinol; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C062018:HU 211