相关实验视频

Updated: Jul 18, 2025

Author Spotlight: Advancing Genetic Epilepsy Studies with Multi-Electrode Array-Based Long-Term Electrophysiological Monitoring of Human Brain Assembloids

Author Spotlight: Advancing Genetic Epilepsy Studies with Multi-Electrode Array-Based Long-Term Electrophysiological Monitoring of Human Brain Assembloids

Published on: September 27, 2024

基于人类前脑器官的PCCB作为与GABAergic通路相关的精神分裂症相关基因的多奥米克分析

Wendiao Zhang^1,2,3,4, Ming Zhang¹, Zhenhong Xu^2,3,4

¹Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.

Nature communications

|August 24, 2023

概括

普罗皮尼尔-CoA碳氧化酶子单元β (PCCB) 的下调可能会通过影响GABAergic通路和线粒体功能来增加精神分裂症 (SCZ) 风险. 这项研究使用人类前脑器官来研究PCCBCB.

科学领域:

神经科学是一个神经科学.
遗传学遗传学是一个
分子生物学分子生物学

背景情况:

精神分裂症 (SCZ) 风险基因通常通过转录全基因组关联研究 (TWAS) 来确定.
作为一种潜在的SCZ风险基因,Propionyl-CoA Carboxylase Subunit Beta (PCCB) 被优先考虑.
在SCZ病原体中PCCB的作用仍然未被探索.

研究的目的:

研究PCCB在精神分裂症 (SCZ) 风险中的功能性作用.
检查SCZ相关的单核酸多态 (SNP) 对PCCB转录活性的影响.
阐明PCCB功能障碍可能导致SCZ的细胞和分子机制.

主要方法:

使用双化酶记者测定来评估SNP对PCCB转录的影响.
PCCB被击倒在人类前脑器官 (hFO) 中.
进行了包括RNA测序,代谢学,线粒体功能的测定和多电极阵列记录在内的多omics分析.

主要成果:

与SCZ相关的SNP (rs6791142,rs35874192) 证明了对PCCB转录活性的差异性基效应.
在hFOs中,PCCB的淘汰导致神经元功能基因的失调,特别是那些在玛-氨基黄油酸 (GABA) -活性突触通路中的基因.
代谢和线粒体分析显示,在PCCB缺乏的hFO中,由于三酸循环抑制,GABA水平下降.
在hFOs中,PCCB knockdown诱导了SCZ相关的表型,包括超神经活动和神经网络同步降低.

结论:

通过破坏GABAergic通路和线粒体功能,PCCB下调可能会导致SCZ风险.
这项研究强调了线粒体功能障碍在SCZ病变发生中的潜在作用.
人前脑器官为研究SCZ相关的基因功能提供了有价值的模型.

更多相关视频

2D and 3D Human Induced Pluripotent Stem Cell-Based Models to Dissect Primary Cilium Involvement during Neocortical Development

2D and 3D Human Induced Pluripotent Stem Cell-Based Models to Dissect Primary Cilium Involvement during Neocortical Development

Published on: March 25, 2022

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs

Published on: March 2, 2018

相关概念视频

Biological Causes of Schizophrenia

Biological Causes of Schizophrenia

Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...

Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders

Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders

Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...