Clodronate Liposomes頻登Nature助力巨噬細胞全新的功能發現

更新時間：2024-12-25 點擊次數：633次

中文摘要：

牽張反射是運動系統的基本組成部分，它協調運動背后的協調肌肉收縮。這個過程的核心是肌梭（MS），這是專門受體，與導靜脈內肌纖維內的張力波動密切相關。MS 中的張力變化會觸發一系列神經元事件，包括感覺 Ia 型傳入神經的初始去極化，隨后導致脊髓內運動神經元的激活1,2。這種神經元級聯反應以肌肉收縮的執行而告終，強調了肌肉骨骼和神經系統之間假定的閉環機制。相比之下，我們在這里報告了在 MS 中發現的具有全新分子和功能特征的新巨噬細胞種群，這些特征表達合成和釋放谷氨酸的機制。使用小鼠交叉遺傳學與光遺傳學和電生理學，我們表明肌梭（MS）巨噬細胞（MSMP）的激活在毫秒時間尺度上驅動本體感覺神經元放電。MSMP 通過激發 MS 的谷氨酸依賴性機制激活脊髓回路、運動神經元和肌肉。此外，MSMP 通過增加谷氨酰胺酶的表達來響應神經和肌肉激活，使它們能夠將肌細胞在肌肉收縮過程中釋放的攝取谷氨酰胺轉化為谷氨酸。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節以產生力和感覺反饋校正，損害了小鼠的運動策略。我們的結果確定了一種新的細胞成分 MSMP，它直接調節神經活動和肌肉收縮。MSMP 的谷氨酸介導的信號傳導及其對感覺線索的動態反應為我們對感覺和運動動作的理解引入了一個新的維度，有可能在影響感覺運動功能的情況下提供創新的治療方法。

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

規格：5ml+5ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

注射方式：Day1一次，Day3一次