PILOT PROJECT--GENE REGULATION IN VASOPRESSIN NEURONS DURING AGING

该研究计划的目标是确定衰老的影响 对加压素（VP）神经元基因表达的影响。 我们已经证明 老年大鼠对慢性脱水的VP反应减弱。 老年大鼠神经叶中VP浓度降低， 合成在老年大鼠中减少。 此外，在患有 阿尔茨海默病，脑脊液中VP减少， VP从神经叶释放存在异常。 这些 观察表明，VP神经元的功能可能会受到损害， 老年痴呆症 几个实验室已经证明，VP mRNA水平增加， 视上核和室旁核的变化 最近的研究表明，核武器 fos蛋白在视上神经元中快速表达， 脱水或血浆渗透压的急性增加。 所以我们 建议检查增加VP分泌的刺激的效果， 视上核和室旁核Fos、fos mRNA和VPmRNA含量的变化 以确定系统是否能够增加VP 响应于慢性刺激的分泌受到损害。 另外我们 建议评估年龄对其他VP的VPmRNA含量的影响 参与记忆过程调节的神经元。 具体 本提案的目的是： 1.为了确定衰老对VP mRNA含量和诱导的影响， 视上核和室旁核fos的表达 脱水 2.确定年龄对视上核fos诱导的影响 和室旁核对渗透压浓度急性增加的反应 细胞外液 3.为了确定衰老对其他细胞VP和VP mRNA含量的影响， 含有产生VP的神经元的核。 这些原子核 评价的是视交叉上核，纹状体床核， 终核和蓝斑。 这些初步研究将表明评估 以VP mRNA、fos mRNA和Fos为指标观察年龄对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VP神经元是合适的。

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.