RESETTING THE BIOLOGICAL CLOCK - MEDIATION OF NOCTURNAL CIRCADIAN SHIFTS BY GLUTAMATE AND NO
RESETTING THE BIOLOGICAL CLOCK - MEDIATION OF NOCTURNAL CIRCADIAN SHIFTS BY GLUTAMATE AND NO
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DOI：
10.1126/science.7527589
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发表时间：
1994-12-09
期刊：
影响因子：
56.9
通讯作者：
GILLETTE, MU
中科院分区：
文献类型：
--
作者：
DING, JM;CHEN, D;GILLETTE, MU
哺乳动物的昼夜节律由位于下丘脑的视交叉上核（SCN）中的内源性时钟计时，其周期约为24小时。光通过每天调整昼夜节律振荡的相位来使这个时钟适应外部环境。该机制被认为涉及从视网膜传入神经到SCN的兴奋性氨基酸的释放。在体外用谷氨酸（Glu）、N-甲基-D-天冬氨酸（NMDA）或一氧化氮（NO）发生器对大鼠SCN进行短暂处理，产生了昼夜节律的光样相移。SCN具有钙依赖性一氧化氮合酶（NOS）活性。NMDA或NOS通路的拮抗剂在体外阻断了Glu的作用，而在体内侧脑室注射NOS抑制剂则阻断了光诱导的行为节律重置。总之，这些数据表明Glu释放、NMDA受体激活、NOS刺激和NO产生将视网膜的光激活与SCN内的细胞变化联系起来，从而介导生物钟的相位重置。
Circadian rhythms of mammals are timed by an endogenous clock with a period of about 24 hours located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Light synchronizes this clock to the external environment by daily adjustments in the phase of the circadian oscillation. The mechanism has been thought to involve the release of excitatory amino acids from retinal afferents to the SCN. Brief treatment of rat SCN in vitro with glutamate (Glu), N-methyl-D-aspartate (NMDA), or nitric oxide (NO) generators produced lightlike phase shifts of circadian rhythms. The SCN exhibited calcium-dependent nitric oxide synthase (NOS) activity. Antagonists of NMDA or NOS pathways blocked Glu effects in vitro, and intracerebroventricular injection of a NOS inhibitor in vivo blocked the light-induced resetting of behavioral rhythms. Together, these data indicate that Glu release, NMDA receptor activation, NOS stimulation, and NO production link light activation of the retina to cellular changes within the SCN mediating the phase resetting of the biological clock.