小柯机器人

神经血管耦合的调控机制
2020-03-03 11:08

哈佛医学院Chenghua Gu课题组的最新研究发现中枢神经系统小动脉中的小窝介导神经血管偶联。该项研究成果在线发表在2020年2月19日出版的《自然》上。

使用双光子显微镜,研究人员观察了清醒小鼠的桶状皮层,在胡须刺激下的成像神经活动和血管动力学;发现小动脉内皮细胞(aECs)在介导神经血管偶联中起正调控作用。研究人员发现与中枢神经系统中内皮细胞的其他血管节段不同,aECs具有丰富的小窝。利用快速遗传干扰清除aEC但非邻近平滑肌细胞(SMC)中的小窝,损害了神经血管耦合。值得注意的是,aEC中小窝的功能独立于内皮一氧化氮合酶(eNOS)介导的一氧化氮途径。小窝和eNOS同时缺失完全消除了神经血管耦合,而单个突变体只表现出部分损伤;这表明aEC中小窝介导的途径是神经血管耦合的主要调控机制。这些发现表明,血管舒张主要是由内皮细胞介导的,它们通过小窝依赖的途径主动将信号从中枢神经系统传递给SMC。

研究人员表示,大脑正常功能的行使取决于神经血管的耦合,即神经活动迅速增加局部血流量以满足局部脑能量需求的瞬时变化。神经血管耦合是大脑成像功能的基础,而神经退行性病变涉及到神经血管耦合受损。但人类对神经血管耦合的潜在分子和细胞机制知之甚少。传统观点认为,神经元或星形胶质细胞释放直接作用于SMC的血管舒张因子,从而诱导动脉扩张并增加局部血流量。

附:英文原文

Title: Caveolae in CNS arterioles mediate neurovascular coupling

Author: Brian W. Chow, Vicente Nuez, Luke Kaplan, Adam J. Granger, Karina Bistrong, Hannah L. Zucker, Payal Kumar, Bernardo L. Sabatini, Chenghua Gu

Issue&Volume: 2020-02-19

Abstract: Proper brain function depends on neurovascular coupling: neural activity rapidly increases local blood flow to meet moment-to-moment changes in regional brain energy demand1. Neurovascular coupling is the basis for functional brain imaging2, and impaired neurovascular coupling is implicated in neurodegeneration1. The underlying molecular and cellular mechanisms of neurovascular coupling remain poorly understood. The conventional view is that neurons or astrocytes release vasodilatory factors that act directly on smooth muscle cells (SMCs) to induce arterial dilation and increase local blood flow1. Here, using two-photon microscopy to image neural activity and vascular dynamics simultaneously in the barrel cortex of awake mice under whisker stimulation, we found that arteriolar endothelial cells (aECs) have an active role in mediating neurovascular coupling. We found that aECs, unlike other vascular segments of endothelial cells in the central nervous system, have abundant caveolae. Acute genetic perturbations that eliminated caveolae in aECs, but not in neighbouring SMCs, impaired neurovascular coupling. Notably, caveolae function in aECs is independent of the endothelial NO synthase (eNOS)-mediated NO pathway. Ablation of both caveolae and eNOS completely abolished neurovascular coupling, whereas the single mutants exhibited partial impairment, revealing that the caveolae-mediated pathway in aECs is a major contributor to neurovascular coupling. Our findings indicate that vasodilation is largely mediated by endothelial cells that actively relay signals from the central nervous system to SMCs via a caveolae-dependent pathway.

DOI: 10.1038/s41586-020-2026-1

Source: https://www.nature.com/articles/s41586-020-2026-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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