Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina’s exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin’s role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved.

ID 21584 Poster Board 473Melatonin (MEL; N-acetyl-5-hydroxytryptamine) and ketamine (KET; 2-(2-chlorophenyl)-2-(methylamino) cyclohexan-1-one) elicit antidepressant-like effects in mice and increases neurogenesis in the hippocampus (HP) through stimulation of MEL receptors or by blocking the NMDA receptors, respectively. Non-effective doses KET administered with non-effective MEL doses, increases both processes.The alpha isoform of Calmodulin-dependent kinase II (CaMKII) is a downstream effector in both KET and MEL signaling pathways. MEL activates CaMKII and stimulates dendrite formation and complexity, as well as neurogenesis in the hippocampus (HP). On the other hand, KET through NMDA receptor antagonism increases pospho-CaMKII (p-CaMKII) levels, and glutamate receptor (GluR1) expression and phosphorylation in the prefrontal cortex (PC). The goal of this study was to determine whether MEL in combination with KET at doses that elicit the anti-depressant-like behavior in mice activates CaMKII and GLUR1 signaling pathways in the HP and PC.Male Swiss Webster mice (25-35 g) were managed under the laboratory animal care rules (NIH-85-23, 1985). Vehicle (VEH), or either MEL (16 mg/kg), or KET (1.5 mg/kg) alone or KET in combination with MEL (1.5/16 mg/kg; KET/MEL) were intraperitoneally administered in 10.0 mL/kg body weight, and 30 min later were submitted to the forced swimming test (FST). Mice were decapitated, and the HP and the PC dissected, homogenized, separated by two-or one-dimensional electrophoresis, and assayed by Western blot. We detected aCaMKII, anti-pCaMKII, GluR1 with specific primary and secondary antibodies coupled to either FITC or RITC. Another group of mice, treated as described above were intracardially perfused with 4% paraformaldehyde after the FST. We sectioned brains with a cryostat at -20 C in slices of 30-35 mm. Slices were stained with the antibodies mentioned above and nuclei with DAPI. Data were analyzed with a Student s t-test or a one-way analysis of variance (ANOVA). p-values # 0.05 was considered as significant.