前列腺素D_2与睡眠调节

Prostaglandin D_2 and sleep regulation

前列腺素Ｄ２(ＰＧＤ２)是目前已知最有潜力的内源性促睡眠物质之一。鼠脑脊液(ＣＳＦ)中ＰＧＤ２浓度与睡眠－觉醒周期一致,呈现节律性改变,并且随睡眠剥夺期间嗜睡倾向增加而增加。催化ＰＧＨ２转变为ＰＧＤ２的待异性酶有两种:Ｌｉｐｏｃａｌｉｎ型前列腺素Ｄ合成酶(Ｌ－ＰＧＤＳ)和脾型ＰＧＤＳ。Ｌ－ＰＧＤＳ主要在大脑蛛网膜和脉络丛产生,并分泌入ＣＳＦ。Ｌ－ＰＧＤＳ和ＰＧＤ_２在脑室系统、蛛网膜下腔及细胞外间隙中循环。循环中的ＰＧＤ２可与前脑头端基底腹内侧面的化学感受器中的前列腺素Ｄ２受体(ＤＰＲ)相互作用,通过活化具有腺苷Ａ２ａ。受体的神经元以产生促进睡眠的信号。ＰＧＤ２敏感区内ＤＰＲ的活化可导致腹侧视前区(ＶＬＰＯ)内神经元的活化,其可通过抑制结节乳头核(ＴＭＮ)而促进睡眠。相反,ＰＧＥ２在维持大脑清醒状态下起主要作用。ＰＧＤ２和ＰＧＥ２的平衡对正常睡眠－觉醒周期的维持十分关键。

Prostaglandin (PG) D2 is recognized as one of the most potent endogenous sleep-promoting substance thus far reported. The PGD2 concentration in rat cerebrospinal fluid (CSF) shows a circadian change coincidant with the sleep-wake cycle and elevates with an increase in sleep propensity during sleep deprivation. The specific enzymes to catalyze the transformation of PGH2 into PGD2 include lipocalin-type prostaglandin D synthase (L-PGDS) and spleen-type PGDS. L-PGDS is dominantly produced in the arachnoid membrane and choroid plexus of the brain, and is secreted into the CSF. L-PGDS as well as the PGD2 thus produced circulates in the venticular system, subarachnoidal space, and extracellular space in the brain. PGD2 then interacts with DP receptors (DPR) in the chemosensory region of the ventro-medial surface of the rostral basal forebrain to initiate the signal to promote sleep probably via the activation of adenosine A2a receptive neurons. The activation of DPR in the PGD2-sensitive chemosensory region results in activation of a cluster of neurons within the ventrolateral preoptic (VLPO) area, which may promote sleep by inhibiting tuberomammillary nucleus (TMN). In contrast, PGE2 plays a significant role in keeping wake. The balance of PGD2 and PGE2 is critical to keep normal sleep-wake cycle.