Circadian clock function as a neuron-glia complex

为了阐明表达GFAP的星形胶质细胞在生物钟中的作用，我们比较了GFAP突变小鼠和野生型小鼠在各种光照条件下的活动节律。GFAP突变小鼠在光暗周期和恒定黑暗中均表现出稳定的昼夜节律，并对环境光刺激表现出正常的夹带。然而，在恒定的光照条件下，GFAP突变小鼠的活动节律的时间比野生型小鼠更长，更中断。HPLC分析显示，在视交叉上核（昼夜节律钟的中心）和中缝核中的多巴胺能活性在GFAP突变小鼠中减少。此外，在恒定光照下饲养80天会降低C57 BL/6 J小鼠视交叉上核中GFAP的表达，同时增加膝状体间小叶中GFAP的表达。这些结果表明，在恒定光照条件下，星形胶质细胞表达的GFAP活性在视交叉上核和膝状体间核中发生了变化。视交叉上核的星形胶质细胞可能通过调节β-肾上腺素能活动在恒定光照条件下维持昼夜节律中发挥重要作用。

In order to clarify the role of GFAP-expressing astrocytes in the circadian clock, we compared the activity rhythms of GFAP mutant mice to those of wild-type mice in various lighting conditions. GFAP mutant mice exhibited stable circadian rhythms both in light-dark cycles and constant darkness and showed normal entrainment to environmental light stimuli. However, under constant lighting conditions, the period of the activity rhythm in GFAP mutant mice was longer and more disrupted than in wild-type mice. HPLC analysis revealed that serotonergic activity in the suprachiasmatic nucleus, which is the center of the circadian clock, and the raphe nuclei was reduced m GFAP mutant mice. Furthermore, housing for 80 days under constant light decreased GFAP expression in the suprachiasmatic nucleus of C57BL/6J mice while increasing GFAP expression in the intergeniculate leaflet. These results demonstrate that the activities of GFAP expressed in astrocytes were changed in the suprachiasmatic nucleus and the intergeniculate nucleus under constant lighting conditions. Astrocytes in the suprachiasmatic nucleus may play important roles in the maintenance of circadian rhythms under constant lighting conditions via regulation of serotonergic activity.