临床前精神分裂症模型中的血清素和谷氨酸相互作用。,ACS Chemical Neuroscience

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临床前精神分裂症模型中的血清素和谷氨酸相互作用。
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2019-03-12 , DOI: 10.1021/acschemneuro.9b00044
Urjita H Shah ₁ , Javier González-Maeso ₁

Affiliation

血清素能和谷氨酸能神经递质系统都与精神分裂症的病理生理学有关，并且有多种证据表明它们可以以功能相关的方式相互作用。特别是，已经证明血清素（5-羟色胺）2A（5-HT2A）受体和代谢型谷氨酸2型（mGlu2）受体可以组装成功能性异聚复合物并调节彼此的功能。这种异聚复合物与致幻剂和抗精神病药的作用机制有关，其作用已在体外和体内系统中得到证实。此外，当配体与异聚复合物结合时，Gi/o 和 Gq/11 蛋白活性变化的差异可用作预测药物的促精神病或抗精神病特性的指标。在精神分裂症受试者死后的人脑样本中，通过异聚体的信号传导失调，这可能与皮质功能的改变有关。mGlu2 和 5-HT2A 受体之间功能串扰的替代途径包括突触和表观遗传机制。本综述重点介绍了过去几年在阐明精神分裂症临床前模型中 5-HT2A 和 mGlu2 受体之间串扰的结构和功能机制方面取得的进展。

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Serotonin and Glutamate Interactions in Preclinical Schizophrenia Models.

The serotonergic and glutamatergic neurotransmitter systems have both been implicated in the pathophysiology of schizophrenia, and there are multiple lines of evidence to demonstrate that they can interact in a functionally relevant manner. Particularly, it has been demonstrated that serotonin (5-hydroxytryptamine) 2A (5-HT2A) receptors and metabotropic glutamate type 2 (mGlu2) receptors can assemble into a functional heteromeric complex and modulate each other's function. This heteromeric complex has been implicated in the mechanism of action of hallucinogens as well as antipsychotic agents, and its role has been demonstrated in both in vitro and in vivo systems. Additionally, the difference in the changes in Gi/o and Gq/11 protein activity when a ligand binds to the heteromeric complex can be used as an index to predict the pro- or antipsychotic properties of an agent. Signaling via the heteromer is dysregulated in postmortem human brain samples of schizophrenia subjects, which may be linked to altered cortical functions. Alternative routes for the functional crosstalk between mGlu2 and 5-HT2A receptors include synaptic and epigenetic mechanisms. This Review highlights the advances made over the past few years in elucidating the structural and functional mechanisms underlying crosstalk between 5-HT2A and mGlu2 receptors in preclinical models of schizophrenia.

更新日期：2019-02-26

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