转录和遗传分析表明,线粒体失调在精神分裂症中的作用
Lisa Bast1, Shuyang Yao2, José A Martínez-López1,3
1Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
medRxiv : the preprint server for health sciences
|March 31, 2025
概括
这项研究揭示了精神分裂症中细胞类型特定的基因表达变化,突出了线粒体功能障碍和神经元中改变的RNA处理作为关键因素. 这些发现推动了我们对精神分裂症的理解.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 精神分裂症是一种复杂的疾病,具有遗传基础和认知缺陷.
- 之前的研究表明神经系统发育受损,以及前额叶皮层的兴奋/抑制不平衡.
- 遗传研究已经确定了许多风险基因,涉及各种细胞类型,包括神经元,星球细胞和微质细胞.
研究的目的:
- 为了研究精神分裂症中细胞类型特定的分子干扰.
- 在精神分裂症中识别出新的,与病因相关的遗传和转录基因变异.
- 将基因分析与单核RNA测序数据相结合.
主要方法:
- 单核RNA测序 (snRNA-seq) 来自43例精神分裂症病例和42例对照的死后背部前额叶皮层 (布罗德曼区域8/9) 的536,618个核.
- 遗传关联和基因表达数据的生物信息分析.
- 在13种细胞类型的共同调节网络分析.
主要成果:
- 没有观察到总体细胞类型丰度的显著差异.
- 激发层2-3和深层脑内神经元表现出最差异化的基因表达,并产生显著的遗传风险.
- 下调的基因在跨膜运输和线粒体功能等途径中得到丰富;在RNA处理中上调的基因.
- 通过神经元亚型,星体细胞和寡细胞共享的基因程序涉及蛋白质修饰,离子运输和线粒体功能.
结论:
- 精神分裂症涉及细胞类型特定的转录基因变化,特别是在刺激神经元中.
- 线粒体功能障碍和RNA处理扰乱是关键的分子特征.
- 综合基因和转录组分析揭示了对精神分裂症病因学的新型细胞类型特定见解.
相关概念视频
Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
302
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...
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...
302
Biological Causes of Schizophrenia
29
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...
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
29
Human Genetics
487
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
487
Mitochondrial Membranes
6.6K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
6.6K
Animal Mitochondrial Genetics
7.4K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.4K
Mitochondria
8.9K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
8.9K


