Activation of P2Y2 Receptors Promotes Neuromuscular Junction Formation during Muscle Reinnervation

IF 0.5 4区 医学 Q4 NEUROSCIENCES Neurochemical Journal Pub Date : 2024-05-27 DOI:10.1134/s1819712424020144
Xianmin Song, Yingna Gao, Wei Wang, Hongliang Zheng, Minhui Zhu, Meng Li, Shicai Chen
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Abstract

Extracellular adenosine 5′-triphosphate (ATP), as neurotransmitter, is known to be an activity-dependent signaling molecule that regulates synaptic signaling. It is known to be co-released with acetylcholine from synaptic vesicle. The P2Y2 receptor (P2Y2R) is present in gastrocnemius muscles and co-localizes with post-synaptic acetylcholine receptors (AChRs). Accumulating evidence indicates that P2Y2R plays crucial roles in assembling neuromuscular junctions (NMJs), a peripheral synapse characterized by the clustering of AChRs on post-synaptic densities. This study investigated the alterations in P2Y2R expression during muscle reinnervation and the effect on NMJ formation. We found that P2Y2R consistently co-localized with AChR and sustained high expression in post-synaptic regions during muscle reinnervation. Notably, PSB1114-dependent stimulation of P2Y2R promoted NMJ formation and muscle reinnervation. The stimulatory effect of PSB1114 was significantly blocked by administration of the P2Y2R antagonist suramin. This study revealed distinctive patterns of expression and localization and a potential role of P2Y2R in promoting NMJ formation and regeneration during skeletal muscle reinnervation.

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激活 P2Y2 受体可在肌肉再支配过程中促进神经肌肉接头的形成
摘要细胞外腺苷-5′-三磷酸(ATP)作为一种神经递质,是一种调节突触信号的活动依赖性信号分子。众所周知,它与乙酰胆碱共同从突触小泡中释放。P2Y2 受体(P2Y2R)存在于腓肠肌中,并与突触后乙酰胆碱受体(AChRs)共定位。越来越多的证据表明,P2Y2R 在神经肌肉接头(NMJs)的组装中发挥着关键作用,NMJs 是一种外周突触,其特点是 AChRs 聚集在突触后密度上。本研究调查了肌肉神经支配过程中 P2Y2R 表达的变化及其对 NMJ 形成的影响。我们发现,在肌肉神经支配过程中,P2Y2R 始终与 AChR 共定位,并在突触后区域持续高表达。值得注意的是,PSB1114 依赖性刺激 P2Y2R 促进了 NMJ 的形成和肌肉神经支配。服用 P2Y2R 拮抗剂苏拉明可显著阻断 PSB1114 的刺激作用。这项研究揭示了 P2Y2R 的独特表达和定位模式,以及 P2Y2R 在骨骼肌神经支配过程中促进 NMJ 形成和再生的潜在作用。
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来源期刊
Neurochemical Journal
Neurochemical Journal 医学-神经科学
自引率
20.00%
发文量
40
审稿时长
>12 weeks
期刊介绍: Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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