Matsumura H, Nakajima T, Osaka T, Satoh S, Kawase K, Kubo E, Kantha S S, Kasahara K, Hayaishi O
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Japan.
Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11998-2002. doi: 10.1073/pnas.91.25.11998.
The site of action for the sleep-promoting effect of prostaglandin (PG) D2 was extensively examined in the brain of adult male rats (n = 231). PGD2 was administered at 100 pmol/0.2 microliter per min for 6 hr (2300-0500 hr) through chronically implanted microdialysis probes or infusion cannulae. Among the administrations of PDG2 by dialysis probes (n = 176), only those (n = 8) to a ventro-rostral part of the basal forebrain by the probes implanted on the midline consistently increased slow-wave sleep (SWS), by 51 +/- 6 min (mean +/- SEM) above the baseline value (111 +/- 11 min). Since this area is separated by a cleft into right and left regions, the results were interpreted to mean that, through this cleft, PGD2 diffused in the subarachnoid space over the adjacent ventral surface, where it had the effect of promoting sleep. When PGD2 was directly infused into the subarachnoid space (n = 55), extraordinary increases exceeding 90 min were consistently attained for the SWS at sites located between 0.5 and 2 mm rostral to the bregma and between 0 and 1.2 mm lateral to the midline defined according to the stereotaxic coordinates adopted from the brain atlas of Paxinos and Watson [Paxinos, G. & Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates (Academic, San Diego)]. Thus, we demarcated a "PGD2-sensitive, sleep-promoting zone" within this region in the ventral surface of the rostral basal forebrain. During the bilateral infusion of PGD2 into the subarachnoid space of this zone, the hourly mean SWS level of the nocturnal animals (n = 6) in the night reached the maximum at the second hour of the infusion period; this maximum hourly SWS level, corresponding to the daytime level of the same animals, lasted until the end of PGD2 infusion.
在成年雄性大鼠(n = 231)的大脑中,对前列腺素(PG)D2促进睡眠作用的作用位点进行了广泛研究。通过长期植入的微透析探针或输注套管,以100 pmol/0.2微升/分钟的剂量给予PGD2,持续6小时(23:00至05:00)。在通过透析探针给予PGD2的实验中(n = 176),只有那些通过中线植入的探针给予基底前脑腹侧-嘴侧部分的实验(n = 8)能持续增加慢波睡眠(SWS),比基线值(111±11分钟)增加51±6分钟。由于该区域被一个裂隙分隔为左右区域,结果被解释为意味着PGD2通过这个裂隙在蛛网膜下腔扩散到相邻的腹侧表面,在那里它具有促进睡眠的作用。当将PGD2直接注入蛛网膜下腔时(n = 55),在根据帕西诺斯和沃森的脑图谱[帕西诺斯,G. & 沃森,C.(1986)《立体定位坐标中的大鼠脑》(学术出版社,圣地亚哥)]采用的立体定位坐标定义的,在脑前囟前方0.5至2毫米以及中线外侧0至1.2毫米之间的位点,SWS持续增加超过90分钟。因此,我们在 Rostral 基底前脑腹侧表面的这个区域内划定了一个“PGD2敏感、促进睡眠区”。在将PGD2双侧注入该区域的蛛网膜下腔期间,夜间动物(n = 6)在夜间的每小时平均SWS水平在注入期的第二小时达到最大值;这个最大每小时SWS水平,相当于同一动物的白天水平,一直持续到PGD2注入结束。