Keck M E, Hatzinger M, Wotjak C T, Landgraf R, Holsboer F, Neumann I D
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Eur J Neurosci. 2000 Apr;12(4):1487-94. doi: 10.1046/j.1460-9568.2000.00030.x.
The ageing process has been shown to have a profound impact on the hypothalamo-neurohypophysial system (HNS) and the hypothalamo-pituitary-adrenocortical (HPA) axis in humans as well as in rodents. Therefore, in this study, the intracerebral and peripheral release patterns of both vasopressin and oxytocin have been studied in aged male Wistar rats under basal conditions and in response to ethologically relevant stressors, using intracerebral microdialysis and chronic blood sampling techniques, respectively. Approximately a twofold higher basal release of arginine vasopressin (AVP) within the hypothalamic paraventricular nucleus (PVN), but not within the supraoptic nucleus (SON), was found in aged rats, whereas basal oxytocin (OXT) release did not differ in comparison with young rats. With increasing age the rise in intra-PVN release of both AVP and OXT was blunted in response to forced swimming. In contrast, the intra-SON release of AVP was unrelated to age. Simultaneously recorded basal secretion of both AVP and OXT from the neurohypophysis into blood was increased in aged rats, with a blunted OXT response to swim stress. Opposed to that, plasma AVP levels remained unchanged in both groups. Basal plasma levels of corticotropin (ACTH) and corticosterone were elevated in aged rats, whereas stress-elicited ACTH and corticosterone responses were indistinguishable. These results indicate age-related changes in the HNS and HPA axis with an enhanced basal activity opposed to a blunted response to stressors with increasing age. The increased basal release of AVP within the PVN suggests a role of intracerebral AVP in age-associated alterations of HPA axis regulation.
衰老过程已被证明对人类和啮齿动物的下丘脑-神经垂体系统(HNS)以及下丘脑-垂体-肾上腺皮质(HPA)轴有深远影响。因此,在本研究中,分别采用脑内微透析和慢性采血技术,研究了老年雄性Wistar大鼠在基础条件下以及对行为学相关应激源反应时血管加压素和催产素的脑内及外周释放模式。在老年大鼠的下丘脑室旁核(PVN)内发现精氨酸血管加压素(AVP)的基础释放量大约是年轻大鼠的两倍,但在视上核(SON)内并非如此,而催产素(OXT)的基础释放量与年轻大鼠相比没有差异。随着年龄的增长,在强迫游泳时,PVN内AVP和OXT的释放增加幅度减弱。相比之下,SON内AVP的释放与年龄无关。同时记录到老年大鼠神经垂体向血液中释放的AVP和OXT的基础分泌增加,且OXT对游泳应激的反应减弱。与此相反,两组的血浆AVP水平均保持不变。老年大鼠促肾上腺皮质激素(ACTH)和皮质酮的基础血浆水平升高,而应激引起的ACTH和皮质酮反应没有差异。这些结果表明HNS和HPA轴存在与年龄相关的变化,基础活性增强,而随着年龄增长对应激源的反应减弱。PVN内AVP基础释放增加表明脑内AVP在HPA轴调节的年龄相关改变中起作用。