海马 CA1 锥体神经元中的 mGluR5 介导应激诱导的焦虑样行为。
mGluR5 in hippocampal CA1 pyramidal neurons mediates stress-induced anxiety-like behavior.
机构信息
State Key Laboratory of Organ Failure Research, Institute of Brain Diseases, Nanfang Hospital, Southern Medical University; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
出版信息
Neuropsychopharmacology. 2023 Jul;48(8):1164-1174. doi: 10.1038/s41386-023-01548-w. Epub 2023 Feb 16.
Pharmacological manipulation of mGluR5 has showed that mGluR5 is implicated in the pathophysiology of anxiety and mGluR5 has been proposed as a potential drug target for anxiety disorders. Nevertheless, the mechanism underlying the mGluR5 involvement in stress-induced anxiety-like behavior remains largely unknown. Here, we found that chronic restraint stress induced anxiety-like behavior and decreased the expression of mGluR5 in hippocampal CA1. Specific knockdown of mGluR5 in hippocampal CA1 pyramidal neurons produced anxiety-like behavior. Furthermore, both chronic restraint stress and mGluR5 knockdown impaired inhibitory synaptic inputs in hippocampal CA1 pyramidal neurons. Notably, positive allosteric modulator of mGluR5 rescued stress-induced anxiety-like behavior and restored the inhibitory synaptic inputs. These findings point to an essential role for mGluR5 in hippocampal CA1 pyramidal neurons in mediating stress-induced anxiety-like behavior.
药物对 mGluR5 的调控作用表明，mGluR5 参与了焦虑症的病理生理学过程，mGluR5 被认为是焦虑症的潜在药物靶点。然而，mGluR5 参与应激诱导的焦虑样行为的机制在很大程度上仍不清楚。在这里，我们发现慢性束缚应激诱导焦虑样行为，并降低海马 CA1 区 mGluR5 的表达。海马 CA1 锥体神经元中 mGluR5 的特异性敲低会产生焦虑样行为。此外，慢性束缚应激和 mGluR5 敲低均损害了海马 CA1 锥体神经元中的抑制性突触传入。值得注意的是，mGluR5 的正变构调节剂挽救了应激诱导的焦虑样行为，并恢复了抑制性突触传入。这些发现表明，mGluR5 在海马 CA1 锥体神经元中对于介导应激诱导的焦虑样行为具有重要作用。
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