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 language | English |
|---|---|
| Pages (from-to) | 83-90 |
| Number of pages | 8 |
| Journal | Amyotrophic Lateral Sclerosis |
| Volume | 11 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - 2010 |
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Keywords
- ALS
- CB1 receptors
- Endocannabinoids
- EPSC
- IPSC
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
Cite this
Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis. / Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Cozzolino, Mauro; Bernardi, Giorgio; MacCarrone, Mauro; Mercuri, Nicola B.; Carrí, Maria Teresa; Centonze, Diego.
In: Amyotrophic Lateral Sclerosis, Vol. 11, No. 1-2, 2010, p. 83-90.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis
AU - Rossi, Silvia
AU - De Chiara, Valentina
AU - Musella, Alessandra
AU - Cozzolino, Mauro
AU - Bernardi, Giorgio
AU - MacCarrone, Mauro
AU - Mercuri, Nicola B.
AU - Carrí, Maria Teresa
AU - Centonze, Diego
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - ALS
KW - CB1 receptors
KW - Endocannabinoids
KW - EPSC
KW - IPSC
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U2 - 10.3109/17482960902977954
DO - 10.3109/17482960902977954
M3 - Article
VL - 11
SP - 83
EP - 90
JO - Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
JF - Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
SN - 1466-0822
IS - 1-2
ER -