PILOT PROJECT--GENE REGULATION IN VASOPRESSIN NEURONS DURING AGING

试点项目——衰老过程中加压素神经元的基因调控

• 批准号: 3746051
• 负责人: CELIA D SLADEK
• 金额: --
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746051
• 关键词: aging; electrolyte balance; genetic regulation; immunocytochemistry; laboratory rat; locus coeruleus; messenger RNA; molecular pathology; neuroendocrine system; neurohypophysis; paraventricular nucleus; peptide hormone biosynthesis; radioimmunoassay; suprachiasmatic nucleus; supraoptic nucleus; thalamus; vasopressins

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.

该研究计划的目的是确定衰老的影响 关于加压素（VP）神经元中的基因表达。 我们已经证明了 VP对慢性脱水的反应在老年大鼠中减弱。 老年大鼠在神经叶中的VP浓度降低，VP 老年大鼠的合成减少。 另外，在患者中 阿尔茨海默氏病，脑脊液中的VP减少，并且 VP从神经叶释放中存在异常。 这些 观察结果表明，VP神经元的功能可能会在 衰老和阿尔茨海默氏病。 几个实验室表明，VP mRNA水平在 慢性盐中的上（儿子）和室室核（PVN） 加载，最近的调查表明核 蛋白质，FOS在上脑神经元中迅速表达 脱水或血浆渗透压急性增加。 因此，我们 建议检查刺激的效果，从而增加VP的分泌 儿子和PVN中的FOS，FOS mRNA和VPMRNA含量的神经叶 在衰老期间，以确定系统是否增加VP的能力 响应慢性刺激的分泌受到损害。 另外，我们 建议评估衰老对其他VP的VPMRNA含量的影响 参与记忆过程调节的神经元。 具体 该提案的目的是： 1。确定对衰老对VP mRNA含量的影响和诱导 对慢性 脱水。 2。确定衰老对衰老诱导的影响 和副脑室核响应急性渗透压的急性增加 细胞外液。 3。确定衰老对其他VP和VP mRNA含量的影响 包含VP产生神经元的细胞核。 将是 评估是肌张力核，纹状体的床核 末端和层层。 这些初步研究将表明评估的可行性 使用VP mRNA，FOS mRNA和FOS索引对衰老对VP神经元的影响 内容。 如果这些研究成功，请进一步评估其他 从神经叶和刺激中释放VP的刺激以及刺激 激活非神经型植物学VP神经元是合适的。