AGING AND ESTROGEN ON BIOGENIC AMINE CELL PHYSIOLOGY

哺乳动物的衰老过程包括神经内分泌的变化， 导致女性生殖功能丧失。 发作 无周期性和不育与一般衰老的发现似乎是一个 与年龄相关的下丘脑-垂体-卵巢功能丧失的后果 功能 提示神经内分泌事件为关键因素 导致雌性大鼠发情周期丧失的因素包括 雌激素受体的改变以及生物胺的变化 中枢神经递质5-羟色胺（5-HT）和去甲肾上腺素（NE） 神经系统 这项研究的目的是增加我们对 大脑中介导这些变化的细胞生理事件， 生殖功能，从而增加了我们对 神经内分泌衰老过程。 我们建议检验这个假设， 对5-HT和NE敏感性的变化在衰老中很重要， 通过评价雌性大鼠的直接 这些神经递质对细胞放电的作用 中缝背核中的含降钙素细胞， 蓝斑内含有去甲肾上腺素的细胞。 细胞外单 单位记录技术和微离子导入药物的应用将是 用于研究这些特定的细胞群在年轻和 中年雌鼠 我们还建议评估雌激素是否可以 直接改变这两个细胞群的放电， 神经元对5-HT和NE在细胞水平上的反应， 衰老 此外，背缝的体外切片制备 细胞核将被用来促进细胞内记录，以确定 雌激素和生物胺可能介导的离子机制 雌性大鼠生殖功能下降。

The aging process in mammalian species includes changes in neuroendocrine function which result in a loss of female reproductive function. The onset of acyclicity and infertility found with general senescence appears to be a consequence of the age-related loss of hypothalamic-pituitary-ovarian function. The neuroendocrine events suggested as critical factors responsible for the loss of estrous cyclicity in the female rat include alteration of estrogen receptors as well as changes in the biogenic amine neurotransmitters serotonin (5-HT) and norepinephrine (NE) in the central nervous system. The objective of this research is to increase our understanding of the cellular physiological events in the brain which mediate these changes in reproductive function and, thereby, add to our general knowledge of neuroendocrine aging processes. We propose to test the hypothesis that changes in sensitivity to 5-HT and NE are important in aging and the development of acyclicity in the female rat by evaluating the direct actions of these neurotransmitters on the cell firing of serotonin-containing cells in the dorsal raphe nucleus and norepinephrine-containing cells in locus coeruleus. Extracellular single unit recording techniques and microiontophoretic drug application will be utilized to investigate these transmitter-specific cell groups in young and middle-aged female rats. We also propose to evaluate whether estrogen can directly alter the firing of these two cell groups and, in turn, modulate neuronal responses to 5-HT and NE at the cellular level with respect to aging. In addition, an in vitro slice preparation of the dorsal raphe nucleus will be utilized to facilitate intracellular recordings to identify the ionic mechanism(s) by which estrogen and biogenic amines may mediate the decline of reproductive function in the female rat.