Melatonin and the human hippocampus, a time dependant interplay

Abstract

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 para-hippocampus 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 para-hippocampus 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.

Melatonin prevents glucocorticoid inhibition of cell proliferation and toxicity in hippocampal cells by reducing glucocorticoid receptor nuclear translocation

“…Melatonin regulates the expression of cell adhesion molecules, serotonin release and the plasticity of pyramidal neurons in the hippocampus. Moreover, MT2 receptor −/− mice lack experiencedependent behaviour and show impaired hippocampal long-term potentiation after theta burst stimulation [40]. Also, patients with Alzheimer's dementia present lower levels of serum melatonin and reduced expression of MT2 melatonin receptors [41].…”

Protective Effect of Melatonin upon Neuropathology, Striatal Function, and Memory Ability after Intracerebral Hemorrhage in Rats

“…Hippocampal neurons have receptors for melatonin (Morgan et al, 1994;Musshoff et al, 2002), and the administration of this hormone is known to alter excitability and synaptic transmission within the hippocampus (Hogan et al, 2001;Musshoff et al, 2002;Wan et al, 1999), and melatonin has been shown to alter hippocampal synaptic plasticity through the MT2-mediated regulation of the adenylate cyclase-protein kinase A (AC-PKA) pathway (Wang et al, 2005). The synaptic plasticity in the hippocampus and other brain regions has recently gained attention as an important means by which melatonin may augment its neuroprotective effects beyond reductions in oxidative stress alone (Baydas et al, 2005;Bob and Fedor-Freybergh, 2008;Fukunaga et al, 2002;Gorfine and Zisapel, 2007;Larson et al, 2006;Talaei et al, 2009;Wang et al, 2005). In light of these findings, and those of this study, there is an urgent need for more high-quality mechanistic studies to further investigate these plasticity processes as a possible means of improving outcomes after ICH.…”

Interaction of visual experience and melatonin in the spatial task learning

“…Overall, since memory-related activation in the hippocampus and parahippocampus are affected by time of day and melatonin, and circadian clock and melatonin implicate in human memory processing during night (Gorfine and Zisapel 2007), it can be concluded that the circadian rhythm modifications may account for the poor performance of both the LR and DR animals.…”

“…Evidences suggest that melatonin could be a regulator in the processes contributing to memory formation and synaptic plasticity in different regions of brain including the hippocampus (Baydas et al 2005b;Chaudhury et al 2005;Wang et al 2005;Larson et al 2006;Gorfine and Zisapel 2007), a part of the brain involved in the learning and memory processing. Electrophysiological studies have also revealed that melatonin may regulate the electrical activity of hippocampal neurons Ozcan et al 2006) and alter synaptic transmission between hippocampal neurons (Wan et al 1999;Hogan et al 2001;El-Sherif et al 2003;Abraham et al 2006).…”