Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis
- 1 January 2010
- journal article
- Published by Taylor & Francis Ltd in Amyotrophic Lateral Sclerosis
- Vol. 11 (1-2), 83-90
- https://doi.org/10.3109/17482960902977954
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.Keywords
This publication has 52 references indexed in Scilit:
- D2Dopamine Receptor Activation Facilitates Endocannabinoid-Mediated Long-Term Synaptic Depression of GABAergic Synaptic Transmission in Midbrain Dopamine Neurons via cAMP-Protein Kinase A SignalingJournal of Neuroscience, 2008
- The prostaglandin E2 EP2 receptor accelerates disease progression and inflammation in a model of amyotrophic lateral sclerosisAnnals of Neurology, 2008
- Cysteine 111 Affects Aggregation and Cytotoxicity of Mutant Cu,Zn-superoxide Dismutase Associated with Familial Amyotrophic Lateral SclerosisOnline Journal of Public Health Informatics, 2008
- Chronic cocaine sensitizes striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptorsEuropean Journal of Neuroscience, 2007
- The CB2 cannabinoid agonist AM‐1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onsetJournal of Neurochemistry, 2007
- Depolarization‐induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2‐arachidonoylglycerolJournal Of Physiology-London, 2006
- Tetrahydrocannabinol‐induced neurotoxicity depends on CB1 receptor‐mediated c‐Jun N‐terminal kinase activation in cultured cortical neuronsBritish Journal of Pharmacology, 2003
- Inflammatory processes in amyotrophic lateral sclerosisMuscle & Nerve, 2002
- Locomotor activity and a conditioned fear responseNeuroReport, 2000
- Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosisNature, 1993