CNS MELATONIN TARGET SITES--CONTROL OF SEASONAL CYCLES

这项研究的目的是确定中枢神经系统的靶点， 褪黑激素（MEL），负责光周期控制 季节性能量平衡和生殖状况。 环境 在许多物种中，这些反应的信号是 昼长，神经内分泌传感器是松果体， 其激素，褪黑激素（MEL）。 它只在夜间分泌， 分泌的持续时间编码了白昼长度。 所以，“冬天一样” 短日（SD）和“夏季样”长日（LD）与长日相关。 和短持续时间MEL信号。 西伯利亚仓鼠将会 研究表明，这种物种在能量上表现出戏剧性的季节性变化， 光周期变化后的调节。 具体目标（SA）1： 破坏假定的中枢神经系统MEL靶位点是否阻断了 的MEL信号？ SA 1的目的是确定涉及的大脑部位 在MEL信号的接收/表达中， 破坏的范围和类型不断缩小， 成年雄性松果体切除（PINX）动物的目标部位受到攻击 使用定时输注范例（TIP）来递送外源性MEL信号 通过s.c.给药途径。 大脑中接受 病变显示MEL结合和/或参与整合 代谢和生殖反应。 一系列病变类型将 可制成：直流电，微刀切割和神经毒素破坏细胞 通道体和通道纤维，只有通道纤维，只有细胞 尸体，分别。 将对每一组进行两组实验 大脑部位SA 1。 第一，SD型抑制性MEL的作用 代谢和生殖反应的信号将被测试， LD饲养的PINX仓鼠（有或无病变），每日MEL或生理盐水 通过TIP的载体输注，而在第二种情况下，LD- 类型的刺激MEL信号对这些反应的影响将通过给出 有或无病变MEL的光退化SD圈养PINX仓鼠 信号通过TIP。 病变诱导的任一预期组阻滞 每个实验中的响应将指示处于 对MEL的接收/表达负责最少 信号了 SA 2：刺激假定的MEL靶位点是否模拟 光周期变化引起的反应？ SA 2的目的是 刺激PINX LD饲养的仓鼠的SD型反应，或回归 SD圈养的光退化PINX仓鼠中的LD型反应， 在显示MEL结合的脑部位进行脑内MEL输注， 其中损伤阻断了上述实验中MEL信号的作用。 例如，如果病变阻断MEL诱导的SD型反应，则仅 长时间脑内注入MEL将引起这些反应; 在同一部位的其他类型的输注则不会。 匡威， 在病变阻止恢复为LD型的脑部位发现 SD圈养的光退化仓鼠中LD MEL信号的状态。 这些发现应该有助于确定如何自然发生的变化， 环境会影响能量平衡和繁殖。

The goal of this research is to identify the CNS target sites of melatonin (MEL) that are responsible for the photoperiodic control of seasonal energy balance and reproductive status. The environmental signal for these responses in many species is the change in the daylength, the neuroendocrine transducer of which is the pineal gland and its hormone, melatonin (MEL). MEL only is secreted at night and in this way the duration of secretion encodes the daylength. Thus, 'winter-like' short days (SD) and 'summer-like' long days (LD) are associated with long and short duration MEL signals, respectively. Siberian hamsters will be studied, a species that exhibits dramatic seasonal changes in energy regulation following changes in the photoperiod. Specific Aims (SA) 1: Does destruction of the putative CNS MEL target sites block the reception of MEL signals? the purpose of SA 1 is to identify brain sites involved in the reception/expression of the MEL signals through a process of successive narrowing of the extent and type of destruction of the targeted sites in adult male pinealectomized (PINX) animals challenged with the timed infusion paradigm (TIP) to deliver exogenous MEL signals via the s.c. route of administration. The brain sites that will receive lesions show MEL binding and/or are involved in the integration of metabolic and reproductive responses. A sequence of lesion types will be made: direct current, microknife cut and neurotoxins to destroy cell bodies and fibers of passage, only fibers of passage, and only cell bodies, respectively. Two sets of experiments will be conducted for each brain site in SA 1. In the first, the effects of SD-type inhibitory MEL signals on metabolic and reproductive responses will be tested by giving LD-housed, PINX hamster with or without lesions daily MEL or saline vehicle infusions via the TIP, whereas in the second, the effects of LD- type stimulatory MEL signals on these responses will be tested by giving photoregressed SD-housed, PINX hamsters with or without lesions MEL signals via the TIP. Lesion-induced blockade of either expected set of responses in each experiment will be indicative of a site that is at least responsible partially for the reception/expression of the MEL signal. SA 2: Does stimulation of putative MEL target sites mimic photoperiod change-induced responses? The purpose of SA 2 is to stimulate SD-type responses in PINX LD-housed hamsters, or the return to LD-type responses in SD-housed, photoregressed PINX hamsters via intracerebral MEL infusions at brain sites that show MEL binding and where lesions block the effects of MEL signals in the above experiments. For example, if a lesion blocks MEL-induced, SD-type responses, then only long duration intracerebral MEL infusions will elicit these responses; other types of infusions at the same site will not. The converse should be found for a brain site where lesions block the return to LD-type status by LD MEL signals in SD-housed photoregressed hamsters. These findings should help determine how naturally-occurring changes in the environment can affect energy balance and reproduction.