为了突触稳定,利用代谢控制:REST/NRSF将糖溶性抑制与刺激性神经传递联系起来
Daniele Ferrante1, Barbara Parisi2, Antonella Marte1,2
1Department of Experimental Medicine, University of Genova, Genova, Italy.
The Journal of physiology
|October 10, 2025
概括
使用2-脱氧-d-葡萄糖 (2DG) 抑制糖解激活REST/NRSF通路,降低刺激性突触强度. 这种代谢调节稳定了神经网络,并提供了控制多动和的潜力.
科学领域:
- 神经科学是一个神经科学.
- 细胞的新陈代谢
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 神经细胞的ATP产生依赖于休息时的氧化酸化和高活性时的糖解.
- 糖解抑制与通过表观遗传调节器REST/NRSF调节相关的过活性有关.
- REST/NRSF通过调节发射和突触活动来抵消神经元过活性的作用,但其代谢激活机制尚不清楚.
研究的目的:
- 调查REST/NRSF在抑制糖解对海马神经元活动的影响中的作用.
- 阐明REST/NRSF代谢激活控制神经元刺激性的机制.
主要方法:
- 用2-脱氧-d-葡萄糖 (2DG) 治疗海马神经元以抑制糖分解.
- 测量NADH/NAD+比率,REST/NRSF表达,以及核转位.
- 电生理学记录唤起和微型刺激后突触电流 (EPSCs/mEPSCs).
- 对GluA2阳性的点尺寸和GluA2表达的分析.
主要成果:
- 2DG治疗降低了NADH/NAD+比率,并增加了REST/NRSF表达和核转位.
- 2DG以依赖于REST/NRSF的方式降低了eEPSC和mEPSC的振幅,而不影响GABAergic输入或神经元发射特性.
- 这种减少与减少GluA2阳性点大小和GluA2表达有关,独立于突触密度变化.
结论:
- 取决于REST/NRSF的途径调解2DG诱导的刺激输入的下调,从而促进神经网络的稳定性.
- 这种机制增强了对神经元过度活动的恒常防御.
- 抑制葡萄糖代谢激活了稳定大脑网络的保护性反应,可能有助于控制发作.
相关概念视频
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.8K
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...
3.8K
01:29Excitatory and Inhibitory Effects of Neurotransmitters
12.6K
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...
12.6K
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
822
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
822
01:26Chemical Synapses
4.3K
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...
4.3K
01:26Chemical Synapses
11.3K
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...
11.3K
01:26Neurochemical Transmission: Sites of Drug Action
3.4K
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...
3.4K