MODEL TO STUDY THE ROLE OF AVP, PKC, AND FOS IN THE SCN

研究 AVP、PKC 和 FOS 在 SCN 中的作用的模型

• 批准号: 6192662
• 负责人: ABEL BULT-ITO
• 金额: $ 5.96万
• 依托单位: UNIVERSITY OF ALASKA FAIRBANKS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6192662
• 关键词: Rodentias; arginine vasopressin; behavioral /social science research tag; biological clocks; body physical activity; circadian rhythms; enzyme inhibitors; ethology; fos protein; genetic strain; glucocorticoids; immunocytochemistry; isozymes; laboratory mouse; photostimulus; protein kinase C; suprachiasmatic nucleus

DESCRIPTION (Adapted from applicant's abstract): The suprachiasmatic nuclei (SCN) are the major "biological clocks" in mammals and control most circadian rhythms expressed by the animal. The role of AVP in the SCN is poorly understood, and the significance of Ca2+-dependent PKC isozymes in SCN function is not known. In the mouse, PKCalpha is present in all AVP-positive and many AVP-negative neurons. PKCalpha may play a role in signaling between AVP-positive and AVP-negative neurons within the SCN through the V1a class of receptors via phosphoinositol turnover and activation of PKC. Divergently selected mouse lines differ in the number of AVP, PKCalpha, and PKCbeta1 neurons in the SCN. The differences in the number of AVP, PKCalpha, and PKCbeta1 neurons in the SCN correlate with several circadian rhythm parameters of wheel-running activity and phase-delay responses to 15-min light pulses in constant darkness. Therefore, these lines represent a unique opportunity to investigate the functional role of AVP and Ca2+-dependent PKC isozymes and light transduction pathways in the SCN by using within-species differences in neuroanatomy and circadian behavior. The following hypotheses will be tested: (1) PKC immunoreactivity is restricted to a distinct group of neuronal phenotypes that also differ among the selected lines. (2) The lines differ in the circadian rhythms in AVP and PKC immunoreactivity in the SCN. (3) The magnitude of the phase-delay response is proportional to the number of cells in the SCN that exhibit Fos induction after a light pulse. (4) Differences in AVP immunoreactivity in the SCN among the lines are correlated with variance in plasma glucocorticoid rhythms. (5) Behavioral differences among the lines are due to different levels of PKC in the SCN. Single and double labeling immunocytochemistry of brain sections containing the SCN will be used. In addition, the variance in plasma glucocorticoid rhythms among the lines will be measured. It will also be determined whether chronic administration of a Ca2+-dependent PKC inhibitor into the SCN can alter circadian parameters of wheel-running activity. This proposal addresses the functional significance of key regulatory mechanisms within the SCN influencing physiological and behavioral traits. It will contribute to the general understanding of how the circadian clock in mammals adapts individual to the earth's day-night cycle and, therefore, will advance issues related to human health.

描述（改编自申请人的摘要）：上核核 （SCN）是哺乳动物中的主要“生物钟”，并且控制大多数 动物表达的昼夜节律。 AVP在SCN中的作用是 知之甚少，以及Ca2+依赖性PKC同工酶的意义 SCN功能尚不清楚。 在鼠标中，pkcalpha都存在 AVP阳性和许多AVP阴性神经元。 Pkcalpha可能在 SCN中AVP阳性和AVP阴性神经元之间的信号传导 通过磷酸肌醇周转率通过V1a类的受体和 PKC的激活。 散发选择的鼠标线的数量有所不同 SCN中的AVP，PKCALPHA和PKCBETA1神经元。 差异 SCN中的AVP，PKCALPHA和PKCBETA1神经元的数量与 车轮运行活动的几个昼夜节律参数 相对于15分钟的光脉冲在恒定黑暗中的相位反应。 因此，这些行是一个独特的机会来调查 AVP和Ca2+依赖性PKC同工酶的功能作用和光 SCN中的转导途径通过使用物种内差异 神经解剖学和昼夜节律行为。 以下假设将是 测试：（1）PKC免疫反应性仅限于一组不同的组 所选线之间也有所不同的神经元表型。 （2） AVP和PKC免疫反应性的昼夜节律线条不同 SCN。 （3）相位播放响应的大小与 光脉冲后表现出FOS诱导的SCN中的细胞数量。 （4）线条中SCN中AVP免疫反应性的差异是 与血浆糖皮质激素节律方差相关。 （5）行为 线之间的差异是由于SCN中的PKC水平不同。 含有脑部的单一和双重标记免疫细胞化学 SCN将被使用。 另外，血浆糖皮质激素的方差 将测量线条中的节奏。 它也将确定 长期给予Ca2+依赖性的PKC抑制剂进入 SCN可以改变轮子活动的昼夜节律参数。 这个建议 解决关键调节机制的功能意义 SCN影响生理和行为特征。 它将做出贡献 对哺乳动物中的昼夜节律如何适应的一般理解 个人到地球夜间周期，因此会进步 与人类健康有关的问题。