Duncan M J, Herron J M, Hill S A
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA.
Brain Res Mol Brain Res. 2001 Mar 5;87(2):196-203. doi: 10.1016/s0169-328x(01)00015-8.
Aging leads to many changes in the expression of circadian rhythms, including reduced amplitude, altered relationship to the environmental illumination cycle, and reduced sensitivity to phase resetting signals. Neuropeptide synthesizing neurons in the suprachiasmatic nucleus (SCN), the principal circadian pacemaker in mammals, play a role in regulating pacemaker function and in coupling the pacemaker to overt circadian rhythms. Aging may alter the activity of neuropeptide neurons in the SCN, which could be reflected in changes in mRNA expression. Therefore, this study investigated whether aging alters the level or rhythm of expression of neuropeptide mRNAs in the SCN of male Syrian hamsters, a well established model for the study of age-related changes in circadian rhythms. Three age groups of hamsters (young [3--5 months old], middle-aged [12--15 months old] and old [19--22 months old] were sacrificed at five times of day. Their brains were dissected and sections through the suprachiasmatic nucleus were prepared and used for in situ hybridization for mRNAs for vasoactive intestinal peptide (VIP), arginine vasopressin (AVP) and somatostatin (SS). Aging selectively decreased the SCN expression of VIP mRNA without affecting AVP mRNA or SS mRNA. Also, only AVP mRNA expression exhibited a robust 24-h rhythm, in contrast to previous findings in other species that VIP mRNA and SS mRNA, as well as AVP mRNA, exhibit 24-h rhythms in the SCN. The present findings suggest that age-related reductions in VIP mRNA expression may contribute to the alterations in entrainment and attenuated sensitivity to phase resetting signals that are characteristic of aging. Furthermore, the results demonstrate that neuropeptide gene expression in the SCN is differentially regulated by aging and varies among species.
衰老会导致昼夜节律表达发生许多变化,包括振幅减小、与环境光照周期的关系改变以及对相位重置信号的敏感性降低。视交叉上核(SCN)中的神经肽合成神经元是哺乳动物主要的昼夜节律起搏器,在调节起搏器功能以及将起搏器与明显的昼夜节律耦合方面发挥作用。衰老可能会改变SCN中神经肽神经元的活性,这可能反映在mRNA表达的变化上。因此,本研究调查了衰老是否会改变雄性叙利亚仓鼠SCN中神经肽mRNA的表达水平或节律,叙利亚仓鼠是研究昼夜节律中与年龄相关变化的一个成熟模型。将三组年龄的仓鼠(年轻组[3 - 5个月大]、中年组[12 - 15个月大]和老年组[19 - 22个月大])在一天中的五个时间点处死。解剖它们的大脑,制备通过视交叉上核的切片,并用于血管活性肠肽(VIP)、精氨酸加压素(AVP)和生长抑素(SS)mRNA的原位杂交。衰老选择性地降低了VIP mRNA在SCN中的表达,而不影响AVP mRNA或SS mRNA。此外,与之前在其他物种中的发现不同,只有AVP mRNA表达呈现出强烈的24小时节律,在其他物种中VIP mRNA、SS mRNA以及AVP mRNA在SCN中均呈现出二十四小时节律。目前的研究结果表明,与年龄相关的VIP mRNA表达降低可能导致了衰老所特有的同步化改变和对相位重置信号的敏感性减弱。此外研究结果表明,SCN中神经肽基因表达受衰老的调控存在差异,并且在不同物种间有所不同。