Melatonin and Hippocampus

     The role of melatonin in the hippocampus

     Specific melatonin binding sites exist in the hippocampus of many species (Niles 1987; Laudon et al. 1988; Anis et al. 1989; Stankov et al. 1991, 1993; Deveson et al. 1992; Nonno et al. 1995) .  As already mentioned, melatonin can bind to many sites on the plasma membrane (MT1, MT2, GABA_A receptors and K⁺ channels), and within the cytoplasm (calmodulin, PKA, PKC, free radicals).  Therefore identification of these binding sites as plasma membrane melatonin receptors has been difficult.

     Cloning of melatonin receptor (Fujieda et al. 1999; Oblap and Olszanska 2001; Wiechmann and Smith 2001) has greatly aided in the identification of melatonin receptors within different tissues .  In the vasculature of the human hippocampus specific MT1 mRNA has been immunohistochemicaly localized (Savaskan et al. 2001).  In hippocampal pyramidal neurons of humans and rodents, MT1 and MT2 receptor mRNA has been found (Mussoff et al. 2002; Savaskan et al. 2001; Wan et al. 1999) .  While presence of mRNA for melatonin receptors indicates that the receptors can be expressed, it does not necessarily indicate that they are functional.

     Studies demonstrating actions of melatonin or its analogues on hippocampal physiology are common (Carnerio and Reiter 1998; El-Sherif et al. 2002; Southgate et al. 1998; Arushanian and Beier 1998; Zamorsjii and Pishak 2000; Won et al. 2000; Ortiz et al. 2001 Hogan et al. 2001; Collins and Davies 1997) .  In the rodent hippocampus, melatonin has been shown to decrease hippocampal activity (Hogan et al. 2001; El-Sherif et al. 2001), and block the induction of LTP (Collins and Davies 1997).  In guinea pig hippocampus, melatonin was shown to lower hippocampal excitability and paired-pulse facilitation by modulating the membrane potential (Zeise and Semm 1985).  These four studies all looked at the effects of melatonin in the micromolar range.  As mentioned previously oral consumption of melatonin can significantly raise levels of melatonin, making these results relevant to the possible effects of melatonin in humans following melatonin ingestion.  Therefore pursuing our goal of evaluating the influence of melatonin on the hippocampal neurons, we used a broad range of concentrations of this neurohormone.

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