Melatonin and the human hippocampus, a time dependant interplay
Melatonin and the human hippocampus, a time dependant interplay
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DOI：
10.1111/j.1600-079x.2007.00446.x
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发表时间：
2007-08-01
影响因子：
10.3
通讯作者：
Zisapel, Nava
中科院分区：
文献类型：
--
作者：
Gorfine, Tali;Zisapel, Nava
褪黑激素作为黑暗信号并参与睡眠/觉醒调节。动物研究证明了褪黑激素对海马体的影响，特别表明褪黑激素参与突触可塑性。我们使用功能性磁共振成像来识别和研究褪黑激素对人类海马体的影响。在 22:00 小时（此时内源性褪黑激素水平正常增加）检查记忆任务期间海马复合体的活动，并与 16:00 小时（此时内源性褪黑激素水平最低）进行比较。评估观察到的激活模式和内源性褪黑激素之间的关系。最后，以双盲、安慰剂对照的交叉方式研究了 22:00 时服用的外源性褪黑激素的效果。我们的研究结果表明，与下午相比，22:00 时左侧海马体的激活显着减少，这与海马体活动的昼夜变化相一致。外源性褪黑激素进一步降低了该区域的激活，仅在此时已经跨过褪黑激素起始阶段的受试者中，并且与内源性褪黑激素水平相关。由于下午服用褪黑激素并未显示出这种效果，因此建议采用时间依赖性效果。相反，在跨过褪黑激素起效阶段的受试者中，左侧海马旁回在 22:00 时的激活程度更高。海马旁激活与个体内源性褪黑激素水平相关，并且不受外源性褪黑激素的进一步影响。这些结果表明，海马体和海马旁体中与记忆相关的激活以不同的方式受到一天中的时间和褪黑激素的影响，并且可能暗示生物钟和褪黑激素在夜间的人类记忆处理中。
Melatonin serves as a signal of darkness and participates in sleep/wake regulation. Animal studies demonstrated effects of melatonin in the hippocampus, particularly suggesting involvement in synaptic plasticity. We used functional magnetic resonance imaging to identify and investigate effects of melatonin in the human hippocampus. Activity in the hippocampal complex during a memory task was examined at 22:00 hr (when endogenous melatonin levels are normally increasing) and compared with 16:00 hr (when endogenous melatonin levels are minimal). The relationship between observed activation patterns and endogenous melatonin was assessed. Finally, the effects of exogenous melatonin administered at 22:00 hr were studied in a double-blind, placebo-controlled crossover manner. Our findings indicate that activation in the left hippocampus at 22:00 hr is significantly reduced compared with afternoon hours compatible with diurnal variation in hippocampal activity. Exogenous melatonin further reduced activation in this region, only in subjects who already crossed the melatonin onset phase at this hour and in correlation with endogenous melatonin levels. As such an effect was not demonstrated with afternoon administration of melatonin, a time depended effect is suggested. Contrary, activation in the left parahippocampus at 22:00 hr was higher in subjects that crossed the melatonin onset phase. Parahippocampal activation correlated with individual endogenous melatonin levels and was not further affected by exogenous melatonin. These results demonstrate that memory related activation in the hippocampus and parahippocampus are affected by time of day and melatonin in a differential manner and may implicate the circadian clock and melatonin in human memory processing during the night.