英国帝国理工学院Simone Di Giovanni和丹麦哥本哈根大学Carmelo Bellardita共同合作，近期取得重要工作进展。他们研究提出，巨噬细胞用谷氨酸激发肌梭以增强运动能力。相关研究成果2024年12月4日在线发表于《自然》杂志上。

据介绍，拉伸反射是运动系统的一个基本组成部分，它协调着运动背后的协调肌肉收缩。肌梭（MS）是这一过程的核心，它是一种专门的受体，能敏锐地捕捉到叶内肌纤维内张力的波动。MS中的张力变化引发了一系列神经元事件，包括感觉型Ia传入神经的初始去极化，随后导致脊髓内运动神经元的激活。这种神经元级联反应最终导致肌肉收缩，强调了肌肉骨骼系统和神经系统之间的闭环机制。

相比之下，研究人员报告了一种新的巨噬细胞群的发现，这些巨噬细胞在MS中具有独特的分子和功能特征，表达了合成和释放谷氨酸的机制。利用小鼠交叉遗传学、光遗传学和电生理学，研究人员发现MS巨噬细胞（MSMP）的激活在毫秒的时间尺度上驱动本体感觉神经元放电。MSMP通过激活MS的谷氨酸依赖机制激活脊髓回路、运动神经元和肌肉。

此外，MSMP通过增加谷氨酰胺酶的表达对神经和肌肉的激活做出反应，使其能够将肌肉收缩过程中肌细胞释放的谷氨酰胺转化为谷氨酸。后肢肌肉中MSMP的选择性沉默或耗竭破坏了力产生和感觉反馈校正的拉伸反射的调节，损害了小鼠的运动策略。

总之，这一研究结果发现了一种新的细胞成分，即MSMP，它直接调节神经活动和肌肉收缩。谷氨酸介导的MSMP信号传导及其对感觉线索的动态反应为人们对感觉和运动动作的理解引入了一个新的维度，可能为影响感觉运动功能的疾病提供创新的治疗方法。

附：英文原文

Title: Macrophages excite muscle spindles with glutamate to bolster locomotion

Author: Yan, Yuyang, Antolin, Nuria, Zhou, Luming, Xu, Luyang, Vargas, Irene Lisa, Gomez, Carlos Daniel, Kong, Guiping, Palmisano, Ilaria, Yang, Yi, Chadwick, Jessica, Mller, Franziska, Bull, Anthony M. J., Lo Celso, Cristina, Primiano, Guido, Servidei, Serenella, Perrier, Jean Franois, Bellardita, Carmelo, Di Giovanni, Simone

Issue&Volume: 2024-12-04

Abstract: The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.

DOI: 10.1038/s41586-024-08272-5

Source: https://www.nature.com/articles/s41586-024-08272-5

来源：科学网  小柯机器人