牽張反射是運(yùn)動系統(tǒng)的基本組成部分，它協(xié)調(diào)運(yùn)動背后的協(xié)調(diào)肌肉收縮。這個過程的核心是肌梭（MS），這是專門受體，與導(dǎo)靜脈內(nèi)肌纖維內(nèi)的張力波動密切相關(guān)。MS 中的張力變化會觸發(fā)一系列神經(jīng)元事件，包括感覺 Ia 型傳入神經(jīng)的初始去極化，隨后導(dǎo)致脊髓內(nèi)運(yùn)動神經(jīng)元的激活1,2。這種神經(jīng)元級聯(lián)反應(yīng)以肌肉收縮的執(zhí)行而告終，強(qiáng)調(diào)了肌肉骨骼和神經(jīng)系統(tǒng)之間假定的閉環(huán)機(jī)制。相比之下，我們在這里報(bào)告了在 MS 中發(fā)現(xiàn)的具有全新分子和功能特征的新巨噬細(xì)胞種群，這些特征表達(dá)合成和釋放谷氨酸的機(jī)制。使用小鼠交叉遺傳學(xué)與光遺傳學(xué)和電生理學(xué)，我們表明肌梭（MS）巨噬細(xì)胞（MSMP）的激活在毫秒時間尺度上驅(qū)動本體感覺神經(jīng)元放電。MSMP 通過激發(fā) MS 的谷氨酸依賴性機(jī)制激活脊髓回路、運(yùn)動神經(jīng)元和肌肉。此外，MSMP 通過增加谷氨酰胺酶的表達(dá)來響應(yīng)神經(jīng)和肌肉激活，使它們能夠?qū)⒓〖?xì)胞在肌肉收縮過程中釋放的攝取谷氨酰胺轉(zhuǎn)化為谷氨酸。后肢肌肉中 MSMP 的選擇性沉默或耗竭破壞了對牽張反射的調(diào)節(jié)以產(chǎn)生力和感覺反饋校正，損害了小鼠的運(yùn)動策略。我們的結(jié)果確定了一種新的細(xì)胞成分 MSMP，它直接調(diào)節(jié)神經(jīng)活動和肌肉收縮。MSMP 的谷氨酸介導(dǎo)的信號傳導(dǎo)及其對感覺線索的動態(tài)反應(yīng)為我們對感覺和運(yùn)動動作的理解引入了一個新的維度，有可能在影響感覺運(yùn)動功能的情況下提供創(chuàng)新的治療方法。

英文摘要：

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.

論文信息：

論文題目： Macrophages excite muscle spindles with glutamate to bolster locomotion

期刊名稱： Nature

時間期卷：Nature（2024）

在線時間：2024年12月4日

DOI：doi.org/10.1038/s41586-024-08272-5

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

注射方式：Day1一次，Day3一次