The intrinsic microglial molecular clock controls synaptic strength via the circadian expression of cathepsin S.
The intrinsic microglial molecular clock controls synaptic strength via the circadian expression of cathepsin S.
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DOI：
10.1038/srep02744
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发表时间：
2013-09-25
影响因子：
4.6
通讯作者：
Nakanishi, Hiroshi
中科院分区：
文献类型：
--
作者：
Hayashi, Yoshinori;Koyanagi, Satoru;Kusunose, Naoki;Okada, Ryo;Wu, Zhou;Tozaki-Saitoh, Hidetoshi;Ukai, Kiyoharu;Kohsaka, Shinichi;Inoue, Kazuhide;Ohdo, Shigehiro;Nakanishi, Hiroshi
小胶质细胞被认为在神经元回路的维持和行为调节中发挥着重要作用。我们发现皮质小胶质细胞含有内在的分子钟，并表现出组织蛋白酶 S (CatS) 的昼夜节律表达，组织蛋白酶 S 是大脑中小胶质细胞特异性的溶酶体半胱氨酸蛋白酶。 CatS 的基因缺失导致小鼠表现出过度运动活动，并消除了皮质神经元突触活动和棘密度的昼夜变化，这些变化在黑暗（清醒）阶段明显高于光明（睡眠）阶段。此外，与重组 CatS 一起孵育显着降低了皮质神经元的突触活性。这些结果表明，小胶质细胞在暗相期间分泌的 CatS 通过改变突触周围环境来降低皮质神经元的棘密度，导致随后的光相期间突触强度的降低。因此，由于未能降低突触强度，CatS 的破坏会诱导过度运动活动。
Microglia are thought to play important roles in the maintenance of neuronal circuitry and the regulation of behavior. We found that the cortical microglia contain an intrinsic molecular clock and exhibit a circadian expression of cathepsin S (CatS), a microglia-specific lysosomal cysteine protease in the brain. The genetic deletion of CatS causes mice to exhibit hyperlocomotor activity and removes diurnal variations in the synaptic activity and spine density of the cortical neurons, which are significantly higher during the dark (waking) phase than the light (sleeping) phase. Furthermore, incubation with recombinant CatS significantly reduced the synaptic activity of the cortical neurons. These results suggest that CatS secreted by microglia during the dark-phase decreases the spine density of the cortical neurons by modifying the perisynaptic environment, leading to downscaling of the synaptic strength during the subsequent light-phase. Disruption of CatS therefore induces hyperlocomotor activity due to failure to downscale the synaptic strength.
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影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
4.8
作者：
Koyanagi, Satoru;Hamdan, Ahmed M.;Ohdo, Shigehiro
通讯作者：
Ohdo, Shigehiro
DOI：
10.1073/pnas.0610811104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Clark, Anna K.;Yip, Ping K.;Malcangio, Marzia
通讯作者：
Malcangio, Marzia
DOI：
10.1073/pnas.1117881109
发表时间：
2012-03-27
影响因子：
11.1
作者：
Irie, Fumitoshi;Badie-Mahdavi, Hedieh;Yamaguchi, Yu
通讯作者：
Yamaguchi, Yu
影响因子：
4.8
作者：
Nishioku, T;Hashimoto, K;Nakanishi, H
通讯作者：
Nakanishi, H