The role of N-methyl-D-aspartate receptors and metabotropic glutamate receptor 5 in the prepulse inhibition paradigms for studying schizophrenia: pharmacology, neurodevelopment, and genetics.
The role of N-methyl-D-aspartate receptors and metabotropic glutamate receptor 5 in the prepulse inhibition paradigms for studying schizophrenia: pharmacology, neurodevelopment, and genetics.
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DOI：
10.1097/fbp.0000000000000352
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发表时间：
2018-02
影响因子：
1.6
通讯作者：
Zhemeng Wu;Zhigang Yang;Mengjiao Zhang;Xiaohan Bao;F. Han;Liang Li
中科院分区：
文献类型：
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作者：
Zhemeng Wu;Zhigang Yang;Mengjiao Zhang;Xiaohan Bao;F. Han;Liang Li
精神分裂症的阳性和阴性症状的治疗已经探索了几十年，但尚未发现完全成功的治疗方法。代谢型谷氨酸受体5（mGluR 5），增强与精神分裂症有关的脑区的N-甲基-D-天冬氨酸受体，已成为治疗精神分裂症的新药物靶点，特别是mGluR 5阳性变构调节剂。精神分裂症患者表现出前脉冲抑制（PPI）的缺陷，这是一种感觉运动门控的操作测量。在这篇综述中，我们专注于药理学，神经发育和遗传动物模型的破坏PPI，目的是显示潜在的作用mGluR 5在调节N-甲基-D-天冬氨酸受体的活性和他们的贡献对精神分裂症的治疗。由于精神分裂症患者PPI的注意调节功能受损与其症状严重程度相关，而基线PPI的注意调节功能受损与其症状严重程度无关，因此本文还强调了PPI注意调节功能的研究对于研究精神分裂症的认知障碍和神经功能障碍至关重要。
Treatments for the positive and negative symptoms of schizophrenia have been explored for decades, but no completely successful therapy has been found as yet. Metabotropic glutamate receptor 5 (mGluR5), which potentiates N-methyl-D-aspartate receptors in brain regions implicated in schizophrenia, has become a novel drug target in the treatment of schizophrenia, especially for the mGluR5-positive allosteric modulators. Individuals with schizophrenia show deficits in prepulse inhibition (PPI), which is an operational measurement of sensorimotor gating. In this review, we focus on pharmacological, neurodevelopmental, and genetic animal models of disrupted PPI, with the aim of showing the potential role of mGluR5 in modulating the activity of N-methyl-D-aspartate receptors and their contributions toward the treatment of schizophrenia. As, the impairment of attentional modulation of PPI, but not that of baseline PPI, in individuals with schizophrenia is correlated with their symptom severity, this review also highlights that investigation of attentional modulation of PPI is critical for studying both cognitive impairments and glutamatergic dysfunctions of schizophrenia.