Arutjunyan A V, Kerkeshko G O, Anisimov V N, Stepanov M G, Prokopenko V M, Pozdeyev N V, Korenevsky A V
D.O. Ott Research Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg, Russia.
Neuro Endocrinol Lett. 2001 Aug;22(4):229-37.
Our data on the contents of norepinephrine (NE), dopamine (DA) and the metabolite of serotonin 5-hydroxyindoleacetic acid (5-HIAA) measured in the suprachiasmatic nuclei (SCN), preoptic area (PA) and median eminence (ME) of hypothalamus of rats after single subcutaneous injection of 1,2-dimethylhydrazine (DMH) as well as the effect of this carcinogen on formation of reactive oxygen species (ROS) in the PA are presented in this paper.
Diurnal changes of DA in all studied brain structures and of NE in the PA have been observed in the control group. Their morning levels were higher than evening ones. Rhythms of 5-HIAA in the SCN and diurnal changes of ROS formation have been shown to have contrary changes in control. Both the morning (11 a.m.) and evening (11 p.m.) subcutaneous administration of DMH at the dose of 21 mg/kg of body weight resulted in changes of all rhythms observed in control. In some cases a phase shift was found, in others the rhythms of neurotransmitters and ROS formation disappeared entirely.
The data obtained confirm the idea of dopaminergic and serotoninergic systems taking part in mechanisms of a response of the hypothalamic nuclei to non-photic stimuli. It is suggested that the effect of DMH on the content and diurnal rhythms of neurotransmitters in the hypothalamic structures under study is due to its affecting activities of the enzymes of biogenic amines synthesis, synaptic transmission, melatonin synthesis and secretion rhythms. The change in ROS formation that is caused by administration of DMH is likely to be due to a disturbance of diurnal rhythms of neurotransmitters that are one of the sources of formation of free radicals in the brain.
本文呈现了在大鼠单次皮下注射1,2 - 二甲基肼(DMH)后,在下丘脑视交叉上核(SCN)、视前区(PA)和正中隆起(ME)中测量的去甲肾上腺素(NE)、多巴胺(DA)以及血清素5 - 羟吲哚乙酸(5 - HIAA)代谢物的含量数据,以及这种致癌物对PA中活性氧(ROS)形成的影响。
在对照组中观察到了所有研究脑区中DA的昼夜变化以及PA中NE的昼夜变化。它们的早晨水平高于晚上水平。已表明SCN中5 - HIAA的节律和ROS形成的昼夜变化在对照组中呈现相反变化。以21mg/kg体重的剂量在上午11点和晚上11点进行DMH皮下给药,均导致了对照组中观察到的所有节律的变化。在某些情况下发现了相位偏移,在其他情况下神经递质和ROS形成的节律完全消失。
所获得的数据证实了多巴胺能和5 - 羟色胺能系统参与下丘脑核团对非光刺激反应机制的观点。提示DMH对所研究的下丘脑结构中神经递质含量和昼夜节律的影响是由于其影响生物胺合成酶的活性、突触传递、褪黑素合成和分泌节律。DMH给药引起的ROS形成变化可能是由于神经递质昼夜节律紊乱,而神经递质是大脑中自由基形成的来源之一。