小柯机器人

日本九州大学Makoto Tsuda及其研究团队发现浅层薄板门脑干中的脊髓星形胶质细胞能够控制机械感觉超敏反应下降。这一研究成果发表在2020年10月5日出版的国际学术期刊《自然-神经科学》上。

他们确定了成年人中位脊髓背角（SDH）浅表层的星形胶质细胞群，这是由Hes5基因定义的。体内成像显示，足底辣椒素注射的有害刺激通过来自蓝斑能量降低的去甲肾上腺素能信号激活了Hes5 + SDH星形胶质细胞，该信号需要通过α1A-肾上腺素能受体（α1A-ARs）传导。鞘内去甲肾上腺素通过Hes5 +星形胶质细胞中的α1A-ARs引起机械性疼痛超敏反应，并且化学上刺激Hes5 + SDH星形胶质细胞足以产生超敏性。

此外，辣椒素诱导的机械性超敏反应通过抑制向Hes5 +星形胶质细胞降低的蓝斑-去甲肾上腺素能信号传导被阻止。此外，在慢性疼痛模型中，Hes5 +星形胶质细胞中的α1A-ARs是确定度洛西汀镇痛作用的关键调节剂。他们的发现确定了一个表面SDH选择性星形胶质细胞群体，该群体控制机械感觉行为的降压肾上腺素能控制。

据介绍，星形胶质细胞是中枢神经系统功能的关键调节器，被认为在发育中的大脑和脊髓中是异质的。

附：英文原文

Title: Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity

Author: Yuta Kohro, Tsuyoshi Matsuda, Kohei Yoshihara, Keita Kohno, Keisuke Koga, Ryuichi Katsuragi, Takaaki Oka, Ryoichi Tashima, Sho Muneta, Takuya Yamane, Shota Okada, Kazuya Momokino, Aogu Furusho, Kenji Hamase, Takumi Oti, Hirotaka Sakamoto, Kenichiro Hayashida, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Hidetoshi Tozaki-Saitoh, Katsuhiko Mikoshiba, Verdon Taylor, Kazuhide Inoue, Makoto Tsuda

Issue&Volume: 2020-10-05

Abstract: 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 by Hes5. In vivo imaging revealed that noxious stimulation by intraplantar capsaicin injection activated Hes5+ SDH astrocytes via α1A-adrenoceptors (α1A-ARs) through descending noradrenergic signaling from the locus coeruleus. Intrathecal norepinephrine induced mechanical pain hypersensitivity via α1A-ARs in Hes5+ astrocytes, and chemogenetic stimulation of Hes5+ SDH astrocytes was sufficient to produce the hypersensitivity. Furthermore, capsaicin-induced mechanical hypersensitivity was prevented by the inhibition of descending locus coeruleus–noradrenergic signaling onto Hes5+ astrocytes. Moreover, in a model of chronic pain, α1A-ARs in Hes5+ 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. Kohro et al. identify a population of astrocytes located in the superficial dorsal horn of adult spinal cord (genetically defined by Hes5) that acts as a gate for locus coeruleus descending noradrenergic control of mechanosensory hypersensitivity.

DOI: 10.1038/s41593-020-00713-4

Source: https://www.nature.com/articles/s41593-020-00713-4

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex