Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system.
Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system.
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DOI：
10.1016/j.neuropharm.2017.10.026
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发表时间：
2018-01
影响因子：
4.7
通讯作者：
Nicoletti F
中科院分区：
文献类型：
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作者：
Di Menna L;Joffe ME;Iacovelli L;Orlando R;Lindsley CW;Mairesse J;Gressèns P;Cannella M;Caraci F;Copani A;Bruno V;Battaglia G;Conn PJ;Nicoletti F
mGlu5受体参与活性依赖性突触可塑性的机制，并且被开发用于治疗CNS病症的药物靶向。我们报告说，mGlu3受体，这是传统上与控制神经递质释放，支持mGlu5受体信号在神经元中，并在很大程度上有助于强大的mGlu5受体介导的多磷酸肌醇水解在出生后的早期生活。在皮质锥体神经元中，mGlu3受体激活增强mGlu5受体介导的体细胞Ca 2+动员，而mGlu3受体介导的前额皮质长期抑郁需要mGlu5受体的内源性激活。mGlu3和mGlu5受体之间的相互作用也与神经元毒性机制有关，mGlu3受体影响mGlu5受体对兴奋性毒性神经元死亡的影响。这些发现揭示了mGlu受体在生理学和病理学中所起的复杂作用，并建议重新考虑mGlu受体领域的一些现有教条。
mGlu5 receptors are involved in mechanisms of activity-dependent synaptic plasticity, and are targeted by drugs developed for the treatment of CNS disorders. We report that mGlu3 receptors, which are traditionally linked to the control of neurotransmitter release, support mGlu5 receptor signaling in neurons and largely contribute to the robust mGlu5 receptor-mediated polyphosphoinositide hydrolysis in the early postnatal life. In cortical pyramidal neurons, mGlu3 receptor activation potentiated mGlu5 receptor-mediated somatic Ca2+ mobilization, and mGlu3 receptor-mediated long-term depression in the prefrontal cortex required the endogenous activation of mGlu5 receptors. The interaction between mGlu3 and mGlu5 receptors was also relevant to mechanisms of neuronal toxicity, with mGlu3 receptors shaping the influence of mGlu5 receptors on excitotoxic neuronal death. These findings shed new light into the complex role played by mGlu receptors in physiology and pathology, and suggest reconsideration of some of the current dogmas in the mGlu receptor field.