Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity
Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity
复制标题
DOI：
10.1038/s41593-020-00713-4
复制
发表时间：
2020-10-05
影响因子：
25
通讯作者：
Tsuda, Makoto
中科院分区：
文献类型：
--
作者：
Kohro, Yuta;Matsuda, Tsuyoshi;Tsuda, Makoto
Kohro等鉴定了一群位于成年脊髓背角浅层的星形胶质细胞（遗传学定义为Hes 5），其作为蓝斑下行去甲肾上腺素能控制机械感觉超敏反应的门，星形胶质细胞是中枢神经系统功能的关键调节因子，并且被认为在发育中的脑和脊髓中是异质的。在这里，我们确定了一个人口的星形胶质细胞位于浅层的脊髓背角（SDH）在成人的遗传定义由Hes 5。体内成像显示，足底注射辣椒素的伤害性刺激通过α（1A）-肾上腺素受体（α（1A）-AR）通过蓝斑下行去甲肾上腺素能信号激活Hes 5（+）SDH星形胶质细胞。鞘内注射去甲肾上腺素通过Hes 5（+）星形胶质细胞中的α（1A）-AR诱导机械性疼痛超敏反应，并且Hes 5（+）SDH星形胶质细胞的化学发生刺激足以产生超敏反应。此外，辣椒素诱导的机械超敏反应可通过抑制Hes 5（+）星形胶质细胞上的蓝斑-去甲肾上腺素能下行信号来防止。此外，在慢性疼痛模型中，Hes 5（+）星形胶质细胞中的α（1A）-AR是决定度洛沙汀镇痛作用的关键调节因子。我们的研究结果确定了一个表面的SDH选择性星形胶质细胞群体，门降去甲肾上腺素控制的机械感觉行为。
Kohro et al. identify a population of astrocytes located in the superficial dorsal horn of adult spinal cord (genetically defined byHes5) that acts as a gate for locus coeruleus descending noradrenergic control of mechanosensory hypersensitivity.Astrocytes are critical regulators of CNS function and are proposed to be heterogeneous in the developing brain and spinal cord. Here we identify a population of astrocytes located in the superficial laminae of the spinal dorsal horn (SDH) in adults that is genetically defined byHes5. In vivo imaging revealed that noxious stimulation by intraplantar capsaicin injection activatedHes5(+)SDH astrocytes via alpha(1A)-adrenoceptors (alpha(1A)-ARs) through descending noradrenergic signaling from the locus coeruleus. Intrathecal norepinephrine induced mechanical pain hypersensitivity via alpha(1A)-ARs inHes5(+)astrocytes, and chemogenetic stimulation ofHes5(+)SDH astrocytes was sufficient to produce the hypersensitivity. Furthermore, capsaicin-induced mechanical hypersensitivity was prevented by the inhibition of descending locus coeruleus-noradrenergic signaling ontoHes5(+)astrocytes. Moreover, in a model of chronic pain, alpha(1A)-ARs inHes5(+)astrocytes were critical regulators for determining an analgesic effect of duloxetine. Our findings identify a superficial SDH-selective astrocyte population that gates descending noradrenergic control of mechanosensory behavior.