Abstract
The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.
Highlights
The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation
We investigated the roles of TRPV1 in the anterior cingulate cortex (ACC) of the rodent brain[31] and we evaluated the impact of neuropathic pain on the channel function
In the present study we found that a monoclonal anti-TRPV1 antibody stained fibers and cell bodies in ACC sections of both adult (n 1⁄4 9 mice; Fig. 1a,b) and young mice (n 1⁄4 8, Supplementary Fig. 1)
Summary
The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. In the cortex of mice suffering from neuropathic pain, TRPV1 is present in neurons affecting their intrinsic electrical properties and synaptic strength. These findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication. With regards to its role in the central nervous system, it is widely accepted that TRPV1 activation mostly modulates synaptic transmission by a presynaptic mechanism[11,12,13,14]. Some work on cultured microglia and microglial cell lines shows that TRPV1 is functionally expressed in brain resident immune cells. TRPV1 causes a variety of effects ranging from microglia cell death to phagocytosis, cell migration, cytokine production and ROS generation[25,26,27,28,29,30]
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