Change in gene expression in glial cells during sleep deprivation

睡眠剥夺期间神经胶质细胞基因表达的变化

• 批准号: 17605012
• 负责人: NAGATA Nanae
• 金额: $ 2.3万
• 依托单位: Osaka Bioscience Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17605012/
• 关键词: forced wakefulness; sleep; sleep deprivation; glial cell; リバウンド

Prostaglandin (PG) D_2 and adenosine are potent humoral sleep-inducing factors that accumulate in the brain during prolonged wakefulness. Adenosine/A_<2A> receptor system plays a pivotal role in the sleep induced by PGD_2. Microarray analysis of expressed genes in the rat brain during sleep induced by intracerebroventricular infusion of PGD_2 or A_<2A> agonist CGS21680 revealed that expression levels of glial cell genes, such as glial fibrillary acidic protein (GFAP), heat shock protein 27 (HSP27), and metallothionein-1 (MT-1), were upregulated.To examine the expression of genes in glial cells, including that of hematopoietic PGD synthase (H-PGDS) and Iba-1 in microglia, and lipocalin-type PGDS (L-PGDS) and pi-GST in oligodendrocytes, we analyzed their levels of mRNA and proteins in the cortex, corpus callosum, hippocampus, thalamus, and hypothalamus of the mouse brain after 6 h of sleep deprivation.Sleep deprivation caused a decrease in mRNA expression of H-PGDS in all the five understudied regions of mouse brain, but not that of GFAP, HSP27, and MT-1. Likewise, expression of Iba-1 mRNA in the thalamus and hypothalamus and pi-GST in the cortex, corpus callosum, and hypothalamus also decreased. Immunoreactivity of H-PGDS and Iba-1 decreased in the microglia of each concerned region. In situ hybridization and immunohistochemical analyses revealed an increase of L-PGDS in oligodendrocytes. These results indicate that gene expression in glial cells deviates during sleep deprivation.

前列腺素 (PG) D_2 和腺苷是有效的体液睡眠诱导因子，在长时间清醒时会在大脑中积聚。腺苷/A_ 2A 受体系统在PGD_2诱导的睡眠中起关键作用。对脑室内注射PGD_2或A_2A激动剂CGS21680诱导的睡眠期间大鼠脑中表达基因的微阵列分析显示，胶质细胞基因的表达水平上调，例如胶质纤维酸性蛋白(GFAP)、热休克蛋白27(H​​SP27)和金属硫蛋白-1(MT-1)。 神经胶质细胞中的基因，包括小胶质细胞中的造血PGD合酶（H-PGDS）和Iba-1，以及少突胶质细胞中的脂运载蛋白型PGDS（L-PGDS）和pi-GST，我们分析了它们在小鼠皮质、胼胝体、海马、丘脑和下丘脑中的mRNA和蛋白质水平 睡眠剥夺 6 小时后的大脑。睡眠剥夺导致小鼠大脑所有五个研究区域中 H-PGDS mRNA 表达下降，但 GFAP、HSP27 和 MT-1 的 mRNA 表达没有下降。同样，丘脑和下丘脑中 Iba-1 mRNA 的表达以及皮质、胼胝体和下丘脑中 pi-GST 的表达也下降。每个相关区域的小胶质细胞中 H-PGDS 和 Iba-1 的免疫反应性均降低。原位杂交和免疫组织化学分析显示少突胶质细胞中 L-PGDS 增加。这些结果表明神经胶质细胞中的基因表达在睡眠剥夺期间发生偏差。