RUI: Circadian Rhythms in NPY and Y5 Receptor Deficient Mice

RUI：NPY 和 Y5 受体缺陷小鼠的昼夜节律

• 批准号: 0234203
• 负责人: Mary Harrington
• 金额: $ 20.01万
• 依托单位: Smith College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0234203&HistoricalAwards=false
• 关键词: RUI; Circadian; Rhythms; NPY; Y5

Mary E. Harrington, 0234203, RUI: Circadian rhythms in NPY and Y5 receptor deficient mice. Biological rhythms are reset each day by external signals to maintain a 24 hour internal cycle. The light:dark cycle is one very important cue for synchronizing these circadian rhythms. Responses to light are mediated through a direct retinal input to the circadian clock, an input that can be modified by other neural inputs. One important modulating neurochemical is neuropeptide Y (NPY). Interactions between NPY and light resetting provide a point of flexibility for adjustments of light entrainment relative to ecological or internal factors.The present research will examine the role of NPY in circadian clock phase resetting by light, making use of mice with deletion of either the NPY gene or the gene for an important NPY receptor, the NPY Y5 receptor. Wheel-running activity rhythms of these mice will be studied and it is expected that NPY- and NPY Y5 receptor-deficient mice will show decreased stability and reliability of entrainment to a light:dark cycle. Mice studied under constant darkness will reveal effects these neurochemicals have on circadian rhythm generation and expression. The mammalian circadian pacemaker is located in the hypothalamic suprachiasmatic nuclei (SCN). Suprachiasmatic nucleus cells maintain a self-sustained oscillation in culture, allowing measures of phase-shifting behavior from an isolated clock. To determine if the Y5 receptor mediates the effects of NPY on light phase shifts, mice with gene deletions will be compared with controls for the effect of NPY applied to the circadian clock in the SCN after a phase shift. It is expected that the Y5 receptor deficient mouse will not show evidence for NPY blocking light-induced phase shifts, providing definitive proof of the importance of this receptor in mediating the effect of NPY on circadian clock resetting.This work relates to the everyday situation of maintaining synchronization with the external 24 h light:dark cycle. Expanding our understanding of the role of NPY in the circadian system will allow better knowledge of the neural basis of flexibility as we adapt to changing environmental cycles. This research will be conducted at an undergraduate college for women, with promising undergraduate women and minorities taking leadership roles in conducting the studies.

玛丽·E·哈林顿，0234203，瑞：神经肽Y和Y5受体缺陷小鼠的昼夜节律。生物节律每天都会被外部信号重置，以维持24小时的内部循环。光：暗周期是同步这些昼夜节律的一个非常重要的线索。对光的反应通过直接的视网膜输入调节到生物钟，这一输入可以被其他神经输入修改。神经肽Y(NPY)是一种重要的神经调节物质。NPY和光重置之间的相互作用为相对于生态或内部因素调节光的夹带提供了一个灵活性点。本研究将利用NPY基因或重要的NPY受体NPY Y5受体的基因缺失的小鼠，研究NPY在光重置昼夜节律时相中的作用。将研究这些小鼠的滚轮活动节律，预计NPY和NPY Y5受体缺陷小鼠将显示出携带到光：暗周期的稳定性和可靠性降低。在持续黑暗中研究的小鼠将揭示这些神经化学物质对昼夜节律产生和表达的影响。哺乳动物的昼夜节律起搏器位于下丘脑视交叉上核(SCN)。视交叉上核细胞在培养中保持自我维持的振荡，允许从一个孤立的时钟测量相移行为。为了确定Y5受体是否介导了NPY对光相移的影响，基因缺失的小鼠将在相移后将NPY应用于SCN的生物钟的效果与对照组进行比较。预计Y5受体缺陷小鼠不会表现出NPY阻断光诱导的相移的证据，这为该受体在介导NPY对昼夜时钟重置的影响中的重要性提供了确凿的证据。这项工作涉及到与外部24小时光：暗周期保持同步的日常情况。扩大我们对NPY在昼夜节律系统中作用的理解，将使我们在适应不断变化的环境周期时，更好地了解灵活性的神经基础。这项研究将在一所本科女子学院进行，有前途的本科生女性和少数族裔将在研究中发挥领导作用。