Abstract
Accumulating evidence supports the role of astrocytes in endocannabinoid mediated modulation of neural activity. It has been reported that some astrocytes express the cannabinoid type 1 receptor (CB1-R), the activation of which is leading to Ca2+ mobilization from internal stores and a consecutive release of glutamate. It has also been documented that astrocytes have the potential to produce the endocannabinoid 2-arachidonoylglycerol, one of the best known CB1-R agonist. However, no relationship between CB1-R activation and 2-arachidonoylglycerol production has ever been demonstrated. Here we show that rat spinal astrocytes co-express CB1-Rs and the 2-arachidonoylglycerol synthesizing enzyme, diacylglycerol lipase-alpha in close vicinity to each other. We also demonstrate that activation of CB1-Rs induces a substantial elevation of intracellular Ca2+ concentration in astrocytes. Finally, we provide evidence that the evoked Ca2+ transients lead to the production of 2-arachidonoylglycerol in cultured astrocytes. The results provide evidence for a novel cannabinoid induced endocannabinoid release mechanism in astrocytes which broadens the bidirectional signaling repertoire between astrocytes and neurons.
Highlights
Accumulating evidence supports the role of astrocytes in endocannabinoid mediated modulation of neural activity
We showed that rat spinal astrocytes both in spinal cord slices and in culture co-express cannabinoid type 1 receptor (CB1-R) and DGLα in close proximity to each other
We demonstrated that activation of CB1-Rs evokes a substantial elevation in [Ca2+]i in micro-domains of processes of cultured astrocytes
Summary
Accumulating evidence supports the role of astrocytes in endocannabinoid mediated modulation of neural activity. It has been reported that some astrocytes express the cannabinoid type 1 receptor (CB1-R), the activation of which is leading to Ca2+ mobilization from internal stores and a consecutive release of glutamate. Though activation of CB1-Rs on astrocytes leads to Ca2+ mobilization[16,17] and Ca2+ transients may evoke the production of 2-AG22–24, 2-AG release from astrocytes evoked by CB1-R activation has never been demonstrated. Filling up these gaps in our knowledge seems important given that endocannabinoid mediated neuron-astrocyte-neuron signaling appears to be crucial in many functions of the central nervous system including pain processing in the spinal dorsal horn. In the present study, we investigated whether spinal astrocytes can release 2-AG in response to activation of their CB1-Rs
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