PILOT PROJECT--GENE REGULATION IN VASOPRESSIN NEURONS DURING AGING

这项研究计划的目的是确定衰老的影响 对加压素(VP)神经元基因表达的影响。我们已经证明了 老年大鼠对慢性脱水的VP反应减弱。 老年大鼠神经叶内VP浓度降低，而VP 老年大鼠的合成减少。此外，在患有 阿尔茨海默病，脑脊液中VP减少， 神经叶的VP释放存在异常。这些 观察表明，VP神经元的功能可能在 衰老和阿尔茨海默氏症。 几个实验室已经证明，Vp mRNA水平在 慢性食盐时视上核(SON)和室旁核(PVN) 装载，最近的调查表明，核子 FOS蛋白在视上神经元中迅速表达 脱水或血浆渗透压急剧升高。因此，我们 建议研究刺激促进肾上腺皮质激素分泌的效果。 SON和PVN神经叶对Fos、FOS和VPmRNA含量的影响 在老化期间，以确定系统是否有能力增加VP 对慢性刺激的反应是分泌受损。另外，我们 建议评估增龄对其他VP的VPmRNA含量的影响 参与记忆过程调节的神经元。具体的 这项建议的目的是： 1.测定衰老对脑组织中VP基因表达的影响，并探讨其对脑损伤的诱导作用 视上核和室旁核FOS在慢性应激反应中的作用 脱水。 2.确定衰老对视上FOS诱导的影响 和室旁核对渗透压急剧升高的反应 细胞外液。 3.测定增龄对大鼠脑内Vp和Vp mRNA含量的影响 含有产生VP的神经元的核团。这些原子核将是 视交叉上核是纹状体的床核 终末核和蓝斑。 这些初步研究将表明评估 用VP、FOS和Fos指标研究增龄对VP神经元的影响 内容。如果这些研究成功，进一步评估其他 从神经叶释放VP的刺激以及 激活非神经垂体区VP神经元将是合适的。

The objective of this research program is to determine the effect of aging on gene expression in vasopressin (VP) neurons. We have demonstrated that the VP response to chronic dehydration is attenuated in aged rats. Aged rats have a decreased concentration of VP in the neural lobe, and VP synthesis is decreased in aged rats. In addition, in patients with Alzheimer's disease, VP is decreased in the cerebrospinal fluid, and abnormalities exist in VP release from the neural lobe. These observations suggest that the function of VP neurons may be compromised in aging and Alzheimer's disease. Several laboratories have demonstrated that VP mRNA levels increase in the supraoptic (SON) and paraventricular nuclei (PVN) during chronic salt loading, and recently investigations have demonstrated that the nuclear protein, fos, is rapidly expressed in supraoptic neurons in response to dehydration or an acute increase in plasma osmolality. Therefore, we propose to examine the effect of stimuli which increase VP secretion from the neural lobe on Fos, fos mRNA and VPmRNA content in the SON and PVN during aging in order to determine if the system's ability to increase VP secretion in response to chronic stimulation is compromised. Also, we propose to evaluate the effect of aging on VPmRNA content of other VP neurons which participate in regulation of memory processes. The specific aims of this proposal are: 1. To determine the effect on aging on VP mRNA content and induction of fos in the supraoptic and paraventricular nuclei in response to chronic dehydration. 2. To determine the effect of aging on induction of fos in the supraoptic and paraventricular nuclei in response to acute increases in osmolality of the extracellular fluid. 3. To determine the effect of aging on VP and VP mRNA content of other nuclei which contain VP producing neurons. The nuclei which will be evaluated are he suprachiasmatic nucleus, the bed nucleus of the stria terminalis, and the locus coeruleus. These preliminary studies will indicate the feasibility of evaluating the effect of aging on VP neurons using indexes of VP mRNA, fos mRNA and Fos content. If these studies are successful, further evaluation of other stimuli for VP release from the neural lobe as well as stimuli which activate the non-neurohypophyseal VP neurons would be appropriate.