Melatonin maintains calcium-binding calretinin-positive neurons in the dentate gyrus during aging of Balb/C mice.

Melatonin, the main product synthesized by the pineal gland, modulates several brain functions through different mechanisms, some of them involving the activation or participation of calcium binding intracellular proteins, such as the alpha calcium dependent protein kinase C and calmodulin. Another calcium-binding protein is calretinin, which exerts an essential role for adult hippocampal neurogenesis. Melatonin favors calretinin-positive neurons in the dentate gyrus (DG) of young mice but hippocampal neurogenesis and plasma levels of melatonin decrease during aging. Thus, in this study, we analyzed the impact of exogenous supplementation with melatonin in calretinin-neurons and their distribution along the dorsal-ventral DG in the hippocampus at three different time points (1, 3, or 6 months) after daily treatment with melatonin (8 mg/kg) in male Balb/C mice. We found an increase in the number of calretinin-positive neurons in the DG after treatment (>66%). Although a significant decline in the number of calretinin-neurons was found in both treated (60.46-69.56%) and untreated mice (68.81-70.34%) with respect to the youngest mice analyzed, melatonin still maintained higher number of cells in the DG. Also, the distribution of calretinin-neurons along the dorsal-ventral DG significantly showed more cells in the ventral-DG of mice treated with melatonin. Together, the data suggest that melatonin also acts on calretinin in the DG, supporting it as a molecule connecting calcium signaling and neuronal development.