通过CDKL5调节神经元激发能力的发育调节,并同时调节转录基因组
Wenlin Liao1,2, Kun-Ze Lee3,4
1Institute of Neuroscience, National Cheng-Chi University, Taipei 116, Taiwan.
Human molecular genetics
|September 9, 2023
概括
缺乏循环林依赖激酶类5 (CDKL5) 的小鼠表现出早期发作的和神经元过敏,为CDKL5缺乏障碍 (CDD) 和潜在的治疗标提供了洞察力.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- 循环素依赖性酶类5 (CDKL5) 对于神经元发育至关重要.
- CDKL5缺乏症 (CDD) 导致严重的神经发育问题,主要是早期发作的.
- 现有的小鼠模型缺乏自发性发作,阻碍了对CDKL5在早期大脑发育中的作用的理解.
研究的目的:
- 在缺乏CDKL5的小鼠中研究早期产后大脑活动.
- 确定与CDKL5缺乏相关的年龄相关和脑区域特定的分子变化.
- 探索CDKL5在新生儿过度兴奋性和方面的作用.
主要方法:
- 在新生小鼠中利用无线EEG遥测和视频录制.
- 在Cdkl5无细胞小鼠的背部海马和运动皮质中进行了无偏向的转录组概况.
- 在转录和蛋白质水平上验证了差异表达的基因.
主要成果:
- 缺乏CDKL5的小鼠在出生后第12天 (P12) 呈现自发性性EEG放电和爆发活动的增加.
- 活动是短暂的,在P14后消失.
- 确定了依赖年龄的,特定区域的基因表达变化,包括甘氨酸受体α2和胆囊托基宁.
结论:
- 在CDD的小鼠模型中证明了早期发作的神经元过敏性.
- 在出生后早期发育中突出过渡性活动.
- 提供了对CDD病因学的见解,并确定了新生儿治疗的潜在分子标.
关键词:
CDKL5缺陷障碍 (CDD) 是一种CDKL5缺陷障碍.在KCC2中,KCC2是KCC2.RNA测序 (RNA-seq) 是指RNA的测序.电脑电图 (EEG) 是一种电脑电图.新生儿发症 新生儿发症更多相关视频
12:01Induction of Protein Deletion Through In Utero Electroporation to Define Deficits in Neuronal Migration in Transgenic Models
Published on: January 12, 2015
10.3K
10:09Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
7.5K
相关概念视频
Regulation of Expression Occurs at Multiple Steps
22.8K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.8K
Regulation of Expression at Multiple Steps
942
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
942
Combinatorial Gene Control
8.4K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.4K
Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
Excitatory and Inhibitory Effects of Neurotransmitters
10.1K
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...
10.1K
Long-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
