在精神分裂症中,前额叶皮层刺激性突触的特定子集的分子组成发生变化
Andrea Lorincz1, Maria Ashaber2, Zoltan Nusser1
1Laboratory of Cellular Neurophysiology, HUN-REN Institute of Experimental Medicine, Budapest 1083, Hungary nusser@koki.hu lorincz@koki.hu.
概括
精神分裂症可能涉及异常的激发性突触传播. 这项研究发现,在精神分裂症患者的特定突触中,NMDA受体密度降低了,这些突触针对精神分裂症患者的parvalbumin内部神经元,这表明它在疾病病理生理学中发挥了作用.
科学领域:
- 神经科学是一个神经科学.
- 分子精神病学分子精神病学
- 突触生物学 突触生物学
背景情况:
- 精神分裂症的病理生理学与前额叶皮层中的异常激发性突触传播有关.
- 突触蛋白水平是突触功能的关键指标,但在人体死后大脑中研究它们是具有挑战性的.
- 以前的研究依赖于遗传证据,缺乏突触水平的直接功能读取.
研究的目的:
- 量化分析人类死后脑组织中个体激发性突触中的关键突触蛋白的密度和亚突触分布.
- 为了比较对照和精神分裂症患者之间的激发性突触的分子组成.
- 调查可能导致精神分裂症的突触变化.
主要方法:
- 优化了高分辨率的定量定位方法,以改善死后脑组织中的抗原识别.
- 利用PSD-95免疫活性作为激发性突触的标志物.
- 量化后突触AMPA和NMDA受体子单元,前突触Bassoon和Munc13-1,以及Munc13-1纳米集群.
主要成果:
- 在对照和精神分裂症患者之间,没有发现总体突触密度,大小或大多数突触蛋白 (PSD-95,AMPA,NMDA,Bassoon,Munc13-1) 的水平有显著差异.
- 显示神经递质释放部位的Munc13-1纳米团的数量在各组之间也相似.
- 与对照人群相比,在精神分裂症患者中观察到NMDA受体密度显著降低,特别是在激发性突触中准表达parvalbumin的内部神经元.
结论:
- 整体激发性突触密度和分子组成在精神分裂症患者的前额叶皮质中在很大程度上保留了.
- 在parvalbumin内部神经元上的突触处NMDA受体密度的特定缺陷可能导致精神分裂症的病理生理学.
- 这项研究强调了检查特定突触子集对于理解复杂的神经疾病的重要性.
更多相关视频
08:27Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
6.3K
09:07Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
12.2K
相关概念视频
01:29Biological Causes of Schizophrenia
146
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...
146
01:27Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
947
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...
947
01:29Excitatory and Inhibitory Effects of Neurotransmitters
10.8K
When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
10.8K
01:03Long-term Depression
2.6K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over...
Calcium Ion Concentration Mechanism
If over...
2.6K
01:29Psychological and Sociocultural Causes of Schizophrenia
185
Schizophrenia, a complex psychiatric disorder, has been historically misunderstood. Early psychological theories attributed its origins to childhood trauma and unresponsive parenting. However, contemporary research largely rejects these notions, favoring the vulnerability-stress hypothesis. This model proposes that individuals with a genetic predisposition to schizophrenia may develop the disorder following exposure to significant environmental stressors. Notably, studies on high-risk...
185
01:26Chemical Synapses
9.1K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
9.1K