Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2024-08-09 DOI:10.3390/ijms25168696

Masaya Yanagi, Mamoru Hashimoto

{"title":"Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators","authors":"Masaya Yanagi, Mamoru Hashimoto","doi":"10.3390/ijms25168696","DOIUrl":null,"url":null,"abstract":"Based on the pathophysiological changes observed in schizophrenia, the gamma-aminobutyric acid (GABA) hypothesis may facilitate the development of targeted treatments for this disease. This hypothesis, mainly derived from postmortem brain results, postulates dysfunctions in a subset of GABAergic neurons, particularly parvalbumin-containing interneurons. In the cerebral cortex, the fast spike firing of parvalbumin-positive GABAergic interneurons is regulated by the Kv3.1 and Kv3.2 channels, which belong to a potassium channel subfamily. Decreased Kv3.1 levels have been observed in the prefrontal cortex of patients with schizophrenia, prompting the investigation of Kv3 channel modulators for the treatment of schizophrenia. However, biomarkers that capture the dysfunction of parvalbumin neurons are required for these modulators to be effective in the pharmacotherapy of schizophrenia. Electroencephalography and magnetoencephalography studies have demonstrated impairments in evoked gamma oscillations in patients with schizophrenia, which may reflect the dysfunction of cortical parvalbumin neurons. This review summarizes these topics and provides an overview of how the development of therapeutics that incorporate biomarkers could innovate the treatment of schizophrenia and potentially change the targets of pharmacotherapy.","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"16 10","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Energy Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/ijms25168696","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}

引用次数: 0

Abstract

Based on the pathophysiological changes observed in schizophrenia, the gamma-aminobutyric acid (GABA) hypothesis may facilitate the development of targeted treatments for this disease. This hypothesis, mainly derived from postmortem brain results, postulates dysfunctions in a subset of GABAergic neurons, particularly parvalbumin-containing interneurons. In the cerebral cortex, the fast spike firing of parvalbumin-positive GABAergic interneurons is regulated by the Kv3.1 and Kv3.2 channels, which belong to a potassium channel subfamily. Decreased Kv3.1 levels have been observed in the prefrontal cortex of patients with schizophrenia, prompting the investigation of Kv3 channel modulators for the treatment of schizophrenia. However, biomarkers that capture the dysfunction of parvalbumin neurons are required for these modulators to be effective in the pharmacotherapy of schizophrenia. Electroencephalography and magnetoencephalography studies have demonstrated impairments in evoked gamma oscillations in patients with schizophrenia, which may reflect the dysfunction of cortical parvalbumin neurons. This review summarizes these topics and provides an overview of how the development of therapeutics that incorporate biomarkers could innovate the treatment of schizophrenia and potentially change the targets of pharmacotherapy.

查看原文本刊更多论文

精神分裂症中功能失调的副发光体神经元以及 Kv3 通道调节剂的临床应用途径

根据在精神分裂症中观察到的病理生理学变化，γ-氨基丁酸（GABA）假说可能有助于开发针对这种疾病的治疗方法。这一假说主要来自于死后大脑的研究结果，假定一部分GABA能神经元，尤其是含副缬氨酸的中间神经元出现功能障碍。在大脑皮层中，副发光素阳性的 GABA 能中间神经元的快速尖峰发射受 Kv3.1 和 Kv3.2 通道调节，它们属于钾通道亚家族。在精神分裂症患者的前额叶皮质中观察到了 Kv3.1 水平的降低，这促使人们开始研究用于治疗精神分裂症的 Kv3 通道调节剂。然而，这些调节剂要想在精神分裂症的药物治疗中有效，还需要能捕捉到副视神经元功能障碍的生物标志物。脑电图和脑磁图研究显示，精神分裂症患者的诱发伽马振荡出现障碍，这可能反映了大脑皮层副白质神经元的功能障碍。本综述总结了这些主题，并概述了结合生物标记物的治疗方法的开发可如何创新精神分裂症的治疗，并有可能改变药物治疗的目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.