周围神经损伤

    Progress in perisynaptic Schwann cell and neuromuscular junction research
  • Figure 1|NG2 and TBX21 expression improves the ability to study normal and pathological responses of PSCs at the NMJ. 

    The neuromuscular junction (NMJ) is widely studied for its utility in investigating synaptic properties and processes and neuromuscular changes in response to injury, aging, and disease. The NMJ consists of three essential anatomic components, the pre-synaptic motor axon terminal, the post-synaptic nicotinic acetylcholine receptors (AchRs) on the muscle, and the perisynaptic Schwann cell (PSC), also known as the terminal Schwann cell, that caps the synapse (Figure 1A). In addition to this tri-partite construction, another cell called the kranocyte is known to be involved in the structural makeup of the NMJ though even less is known about this cell type. The PSC is a protective cellular covering for the NMJ and serves various dynamic functions under normal and pathological conditions. The NMJ is a complex multi-component site of communication between motor axons and target musculature. The PSC is a specialized non-myelinating Schwann cell that protects, nourishes, and regulates synaptic function at the NMJ (Alvarez-Suarez et al., 2020). A dynamic reciprocal communication network exists between the PSC and muscle to adapt to and help modulate alterations to NMJ activity in healthy adults. The PSC produces and secretes trophic factors that influence the axon’s health, post-synaptic muscle, and overall integrity of the NMJ. Likewise, muscle also secretes trophic factors and other chemical mediators that influence the PSC and associated localized structures at the NMJ. 
    These interactions also directly affect PSCs to aid in neuromuscular reinnervation following nerve injury. Retraction of the motor axon terminals and Wallerian degeneration of the axonal segments distal to the injury site occurs acutely and rapidly post-injury. As part of this early response, localized acetylcholine decreases, and the PSC becomes activated and modifies its biochemistry and morphology. Some changes include an upregulation of glial fibrillary acidic protein and neuregulin-1/Erb receptor signaling as the extended cytoplasmic processes of the PSC interact with and guide the regenerating axon toward its muscular target. Trophic factors and guidance cues produced by activated PSCs can also directly influence neuromuscular reinnervation (Figure 1B). The result is PSC-facilitated reinnervation and reestablishment of the NMJ. Expression of G-coupled protein receptor, GPR126, by PSCs improves the ability of axons to successfully reinnervate NMJs after injury, with evidence suggesting it affects trophic factor production and influences target skeletal muscle chemokine and inflammatory response (Jablonka-Shariff et al., 2020). However, the extent of GPR126 expression fluctuations in PSCs over time post-injury is unclear. The correlation between its expression and changes in other components of the NMJ that influence regenerating motor axon innervation requires further investigation (Figure 1B). 


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  • 发布日期: 2021-12-17  浏览: 510
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