TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice.
TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice.
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DOI：
10.1038/ncomms15292
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发表时间：
2017-05-10
影响因子：
16.6
通讯作者：
Marinelli S
中科院分区：
文献类型：
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作者：
Marrone MC;Morabito A;Giustizieri M;Chiurchiù V;Leuti A;Mattioli M;Marinelli S;Riganti L;Lombardi M;Murana E;Totaro A;Piomelli D;Ragozzino D;Oddi S;Maccarrone M;Verderio C;Marinelli S
辣椒素受体 TRPV1 在感觉系统中被广泛认为是疼痛和炎症的关键成分。大量证据表明 TRPV1 在大脑中也有功能，尽管其作用仍存在争议。在这里，我们报告TRPV1在小胶质细胞而不是前扣带皮层和其他大脑区域的神经元中高度表达。我们发现，刺激小胶质细胞 TRPV1 本身可以控制皮质小胶质细胞的激活，并通过促进细胞外小胶质细胞微泡脱落来间接增强神经元中的谷氨酸能传递。相反，在患有神经性疼痛的小鼠的皮层中，TRPV1 也存在于神经元中，影响其内在电特性和突触强度。总而言之，这些发现表明大脑 TRPV1 是有害刺激的潜在探测器，也是小胶质细胞与神经元通讯的关键参与者。 TRPV1 已知在外周结构和脊髓中表达，特别是在疼痛处理方面。作者在此表明，在大脑中，特别是前扣带皮层，TRPV1 在小胶质细胞中进行功能性表达； TRPV1 的刺激会激活小胶质细胞，进而影响谷氨酸能神经传递。
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. TRPV1 is known to be expressed in peripheral structures and the spinal cord, especially for pain processing. Here the authors show that in the brain, in particular the anterior cingulate cortex, TRPV1 is functionally expressed in microglia; stimulation of TRPV1 activates microglia, which in turn affects glutamatergic neurotransmission.