Melatonin increases cell proliferation in the dentate gyrus of maternally separated rats

Abstract

Melatonin in mammals, produced by the pineal gland and elsewhere, has shown antioxidant and neuroprotective properties in neuronal cells. We investigated whether melatonin would increase newly born cells (cell proliferation) in the dentate gyrus of maternally separated rats. To examine the effect of melatonin on cell proliferation of the dentate gyrus in maternally separated rats, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was performed. Rat pups were separated from their mothers and socially isolated on postnatal day 14. Melatonin (10 mg/kg, i.p.) and BrdU (50 mg/kg, i.p.) were given to them for 7 days. The number of BrdU-positive cells was significantly increased in the dentate gyrus of maternally separated pups with melatonin administration (P < 0.001). In addition, the expression of glucocorticoid receptor was significantly decreased in the dentate gyrus compared with maternally separated pups not given melatonin (P < 0.001). This is the first report that melatonin increases cell proliferation in the dentate gyrus of maternally separated rats.

Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice

“…These results were in some contrast to another study, in which melatonin reportedly increased cell proliferation in the dentate gyrus of maternally separated young rats and in non-separated rats after 7 days treatment (Kim et al, 2004). Besides the species differences that study also used a cumulative BrdU-labeling protocol, blurring the distinction between proliferation and survival effects.…”

“…Melatonin modulated proliferative activity in the dentate gyrus in early postnatal rats (Kim et al, 2004) and influenced proliferation and differentiation of embryonic neural stem cells (Moriya et al, 2007). In addition, melatonin increased differentiation of rat midbrain neural stem cells (Kong et al, 2008).…”

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

“…More recently it has been reported that exogenous melatonin could increase the survival of neuronal progenitor cells and postmitotic immature neurons in the hippocampus of adult mice (Ramírez-Rodríguez et al, 2009), consistent with melatonin actions on proliferative activity in the rat dentate gyrus and embryonic neural stem cells (Kim et al, 2004;Moriya et al, 2007). These findings are particularly interesting in view of the recent reports that melatonin can reduce learning and memory deficits in mice models of Alzheimer disease (Feng et al, 2004;Olcese et al, 2009).…”

Neuroprotective Effect of Melatonin on Glucocorticoid Toxicity in the Rat Hippocampus

“…Recently, exogenous melatonin was reported as effective in preventing hippocampal neuronal death and cognitive dysfunction that follow maternal deprivation in the developing rat, a situation involving increased GC levels, over-expression of GC *Address correspondence to this author at the Departamento de Fisiología, Facultad de Medicina, UBA, Paraguay 2155, 1121 Buenos Aires, Argentina; Tel/Fax: 54-11-59509611; E-mail: dcardinali@fmed.uba.ar receptor genes, and oxidative stress [13]. Indeed, melatonin decreased the expression of GC receptor and increased cell proliferation in the dentate gyrus of maternally deprived neonatal rats [14].…”