The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors
The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors
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DOI：
10.1111/j.1460-9568.2010.07186.x
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发表时间：
2010-05-01
影响因子：
3.4
通讯作者：
Franklin, Kathleen M.
中科院分区：
文献类型：
--
作者：
Duncan, Marilyn J.;Hester, James M.;Franklin, Kathleen M.
昼夜节律中与光相关的变化，包括光相移的衰减，与视交叉上核（SCN）中的中枢起搏器的变化相关。衰老降低了血管活性肠肽（VIP）的mRNA表达，VIP是节律产生和光相移的关键神经肽，并增加了5-羟色胺转运体和5-HT 1B受体的表达，其活化抑制了这些相移。在这里，我们描述了仓鼠的研究表明，老化降低SCN胃泌素释放肽的mRNA表达，这也调节光相位重置。由于5-羟色胺神经支配营养支持SCN VIP mRNA的表达，5-羟色胺转运蛋白降低细胞外5-羟色胺，我们预测，长期给予的选择性再摄取抑制剂，氟西汀，将减弱SCN VIP mRNA表达和5-HT 1B受体的年龄相关性变化。原位杂交研究表明，氟西汀治疗不改变SCN VIP mRNA的表达，在任何年龄组，在Zeitgeber时间（ZT）6或13（ZT 12对应于熄灯）。然而，受体放射自显影研究表明，氟西汀可防止ZT 6时SCN 5-HT 1B受体的年龄相关性增加，并在ZT 13时降低两个年龄段的SCN 5-HT 1B受体。因此，衰老对SCN VIP mRNA和SCN 5-HT 1B受体的影响受到不同的调节;与年龄相关的5-羟色胺转运体位点的增加介导了后者，而不是前者。研究还表明，与先前报告的急性氟西汀治疗的相位重置相反，衰老和慢性氟西汀治疗减少了每日轮跑总量，而不改变昼夜轮跑节律的相位。
Age-related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5-HT1B receptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin-releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin-selective reuptake inhibitor, fluoxetine, would attenuate the age-related changes in SCN VIP mRNA expression and 5-HT1B receptors. In situ hybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age-related increase in SCN 5-HT1B receptors at ZT6, and decreases SCN 5-HT1B receptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5-HT1B receptors are differentially regulated; the age-related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment.