Change in gene expression in glial cells during sleep deprivation

前列腺素（PG） d2和腺苷是有效的体液性睡眠诱导因子，在长时间清醒时在大脑中积累。腺苷/A_<2A>受体系统在PGD_2诱导的睡眠中起关键作用。脑室内灌注PGD_2或A_<2A>激动剂CGS21680诱导大鼠睡眠时脑内表达基因的微阵列分析显示，神经胶质纤维酸性蛋白（GFAP）、热休克蛋白27 （HSP27）、金属硫蛋白1 （MT-1）等神经胶质细胞基因表达水平上调。为了检测小胶质细胞中造血PGD合成酶（h -PGDS）和Iba-1基因的表达，以及少突胶质细胞中脂质体型PGDS （L-PGDS）和pi-GST基因的表达，我们分析了睡眠剥夺6 h后小鼠大脑皮层、胼胝体、海马、丘脑和下丘脑中它们的mRNA和蛋白水平。睡眠剥夺导致H-PGDS mRNA在小鼠大脑5个未研究区域的表达减少，但GFAP、HSP27和MT-1的mRNA表达没有减少。同样，丘脑和下丘脑中Iba-1 mRNA的表达以及皮层、胼胝体和下丘脑中pi-GST的表达也有所下降。各相关区域小胶质细胞中H-PGDS和Iba-1的免疫反应性降低。原位杂交和免疫组化分析显示少突胶质细胞中L-PGDS升高。这些结果表明，神经胶质细胞的基因表达在睡眠剥夺时偏离。

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.