GENETIC APPROACH TO CIRCADIAN RHYTHMS IN DEPRESSION

抑郁症昼夜节律的遗传方法

• 批准号: 6165133
• 负责人: AMY E EASTON
• 金额: $ 2.47万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6165133
• 关键词: REM sleep; behavioral /social science research tag; behavioral genetics; biological clocks; circadian rhythms; depression; environmental stressor; gene mutation; genetic regulation; genetically modified animals; heterozygote; homozygote; laboratory mouse; mutant; photostimulus; sleep deprivation; stress

DESCRIPTION (applicant's abstract): Depression has been linked to abnormalities in circadian rhythms in humans and in animal models of depression; however, it is unknown whether a dysfunctional circadian pacemaker can contribute to the development/or severity of depressive symptoms or if circadian rhythm alterations are secondary to the primary cause of the depression. Our laboratories have developed a line of mice harboring a mutation in the Clock gene, a gene that is crucial to normal functioning of the circadian pacemaker. When placed in constant darkness/constant light, Clock mutant heterozygotes exhibit a lengthened period of 25 hours and Clock mutant homozygotes exhibit a lengthened period of 27-28 hours and become arrhythmic after about three weeks in constant conditions. Preliminary studies of sleep in Clock mutant mice have shown that they have decreased total sleep which can be attributed to a decrease in sleep during the light period, but no overall changes in N-REM and REM sleep. The discovery of the Clock mutant mouse as well as having the capability to record sleep from mice puts us in a unique position to test two hypotheses: 1) whether alterations in the circadian pacemaker can contribute to the development of and/or the severity of depressive-like symptoms in an animal model of depression, and 2) whether sleep deprivation, known to have an anti-depressive effect, will attenuate depressive-like symptoms in mice with an altered circadian pacemaker. To test these hypotheses, our laboratory has already established a model of chronic, unpredictable stress in mice and has validated the use of the pedestal-over-water technique as a method of sleep deprivation in mice. These experiments will further the understanding of the relationship between circadian rhythms and depression, thus providing insight on the development of novel therapeutic treatments of depression.

描述（申请人摘要）：抑郁症与 在人类和动物模型中的昼夜节律异常 抑郁症;然而，目前尚不清楚是否是功能失调的昼夜节律 起搏器可能会导致抑郁症的发展/或严重程度 症状或昼夜节律改变是否继发于原发性 抑郁症的原因。我们的实验室培育了一系列老鼠 在时钟基因中隐藏着一个突变，这个基因对正常的 生理节律起搏器的功能当放置在常数 在黑暗/恒定光照下，Clock突变杂合子表现出延长的 25小时的时间和时钟突变纯合子表现出延长的 27-28小时，约三周后出现腹泻， 恒定的条件。Clock突变小鼠睡眠的初步研究 他们的睡眠总量减少， 在光照期睡眠减少，但没有整体变化 在N-REM和REM睡眠中。Clock突变小鼠的发现 因为有能力记录老鼠的睡眠， 位置来测试两个假设：1）昼夜节律的改变是否 起搏器可能导致以下疾病的发展和/或严重程度 抑郁症动物模型中的抑郁样症状，和2） 睡眠剥夺是否有抗抑郁作用， 减轻昼夜节律改变的小鼠的抑郁样症状 起搏器为了验证这些假设，我们的实验室已经 在小鼠中建立了慢性不可预测的应激模型， 验证了水上基座技术作为一种方法的使用 睡眠剥夺小鼠。这些实验将进一步 了解昼夜节律与 抑郁症，从而提供了对小说发展的见解 抑郁症的治疗方法