星球细胞向连xin43 Hemichannel 抑制 防止 辐射诱导 能量载体 减少 神经元和星球细胞 proBDNF 运输到突触
Steffi Schumacher1, Sara Neyt2, Christian Vanhove2
1Physiology Group, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium.
Glia
|July 24, 2025
概括
放射治疗通过破坏葡萄糖运输和增加有害的亲BDNF来损害大脑功能. 使用TAT-Gap19准星细胞连xin 43 (Cx43) 半通道可以防止这些负面影响,在照射后保护神经功能.
科学领域:
- 神经科学是一个神经科学.
- 放射治疗研究 放射治疗研究
- 细胞生物学 细胞生物学
背景情况:
- 脑瘤的放射治疗导致血脑屏障 (BBB) 泄漏和神经元功能障碍.
- 早期的辐射后效应涉及天体细胞-神经元轴的变化.
研究的目的:
- 研究大脑X辐射对天体细胞-神经元轴的影响.
- 确定辐射诱导的神经元功能障碍背后的机制.
- 评估向星细胞连接素43 (Cx43) 半通道的治疗潜力.
主要方法:
- 在辐射后24小时 (20 Gy) 分析了动物大脑切片.
- 神经元和天体细胞载体的免疫特征 (GLUT3,MCT2,GLUT1).
- 评估18F-脱氧葡萄糖的吸收和电脑电图 (EEG) 记录.
- 测量亲脑衍生神经营养因子 (proBDNF) 水平和膀运输.
主要成果:
- 辐射降低了神经元GLUT3和MCT2的表达,但并没有降低神经细胞GLUT1.1.
- 照射后大脑葡萄糖吸收和EEG功率下降.
- 增加了ProBDNF水平,增强了星球细胞囊泡运输和释放.
- 用Cx43半通道阻塞剂TAT-Gap19进行预治疗,预防了所有观察到的神经元和功能变化.
结论:
- 星球细胞是减轻辐射诱导的大脑损伤的关键目标.
- 使用Gap19抑制Cx43半通道泄漏,可以防止大脑葡萄糖处理中出现的干扰.
- 阻断Cx43可以防止辐射诱导的proBDNF转运变化,从而保持神经功能.
相关概念视频
Excitatory and Inhibitory Effects of Neurotransmitters
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 specific...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Neurochemical Transmission: Sites of Drug Action
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...


