Neuropeptide Y blocks serotonergic phase shifts of the suprachiasmatic circadian clock in vitro.

Neuropeptide Y blocks serotonergic phase shifts of the suprachiasmatic circadian clock in vitro.
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神经肽 Y 在体外阻断视交叉上生物钟的血清素能相移。

DOI:
10.1016/s0006-8993(98)00808-7
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发表时间:
1998
期刊:
影响因子:
2.9
通讯作者:
Prosser,RA
Prosser,RA
中科院分区:
医学3区
文献类型:
--
作者:
Prosser,RA

文献摘要

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哺乳动物视交叉上核(SCN)中的昼夜节律起搏器可以通过各种神经化学刺激在体外重置。本研究调查了神经肽 Y (NPY) 和血清素 (5-HT) 激动剂单独使用时的相移特性,以及它们对时钟重置的综合影响。在体外,这些神经递质在白天使用时均已被证明可以提前 SCN 时钟。通过监测体外 SCN 神经元活动节律,我首先确认 5HT1A/5HT7 激动剂 (+)DPAT 在 zeitgeber 时间 6 (ZT6) 时最大程度地提前 SCN 时钟。相反,当在 ZT 10 处应用时,仅 NPY 阶段会提前神经元活动节律。这种效果是通过刺激 Y2 受体而发生的。 NPY 再次通过 Y2 受体发挥作用,阻断 (+)DPAT 诱导的 ZT 6 相移,而 (+)DPAT 和 5-HT 都不影响 NPY 诱导的 ZT 10 相移。NPY 似乎通过阻止环 AMP 的增加来阻断 (+)DPAT 诱导的相移。这些数据首次证明了大鼠白天重置刺激之间的体外相互作用,并为控制生物钟相位的机制提供了重要的见解。
The mammalian circadian pacemaker in the suprachiasmatic nuclei (SCN) can be reset in vitro by various neurochemical stimuli. This study investigated the phase-shifting properties of neuropeptide Y (NPY) and serotonin (5-HT) agonists when applied alone, as well as their combined effects on clock resetting. These neurotransmitters have both been shown to advance the SCN clock in vitro when applied during the daytime. By monitoring the SCN neuronal activity rhythm in vitro, I first confirm that the 5HT1A/5HT7agonist (+)DPAT maximally advances the SCN clock when applied at zeitgeber time 6 (ZT6). Conversely, NPY only phase advances the neuronal activity rhythm when applied at ZT 10. This effect occurs through stimulation of Y2receptors. NPY, again acting through Y2receptors, blocks (+)DPAT-induced phase shifts at ZT 6, while neither (+)DPAT nor 5-HT affect NPY-induced phase shifts at ZT 10. NPY appears to block (+)DPAT-induced phase shifts by preventing increases in cyclic AMP. These data are the first to demonstrate in vitro interactions between daytime resetting stimuli in the rat, and provide critical insights into mechanisms controlling circadian clock phase.