Aim: 

Stress has been related to psychopathology disorders. Stress hormones modulate brain function by changing the structure of neurons and affecting neurogenesis. Among brain cells, hippocampal cells are rich in glucocorticoid receptors where they regulate excitability and suppress adult hippocampal neurogenesis. The dysfunction of the hippocampus could result in some of cognitive and memory deficits observed in some disorders as in Alzheimer's disease. Glucocorticoids, in addition to their role in neurogenesis, enhance neurons vulnerability to different types of neurological insults. Since, the pineal neuroindole melatonin reduces the affinity of glucocorticoid receptors in rat brain and prevents glucocorticoid-induced apoptosis in thymocytes, we study the ability of melatonin to prevent glucocorticoid-induced cell death in hippocampal cells.

Methods: 

By using a cellular mouse model of hypocampal cells, HT22, we study the enhancement of amyloid b_25-35 protein toxicity by dexamethasone when melatonin was present or absent in culture media. Toxicity was study by MTT assay, cell proliferation was study by cell counting and cell cycle analyzed by flow cytometer. Also, glucocorticoid receptor nuclear translocation was study by immunocytochemistry and western-blot.

Results: 

We found a G1/G0 cell cycle arrest mediated by an increase of cyclin/cyclin-dependent kinase inhibitor p21^WAF1/CIP1 protein levels after dexamethasone treatment. Melatonin, at physiological concentrations, prevented glucocorticoid inhibition of cell proliferation and reduced the toxicity caused by glucocorticoids when cells were treated with dexamethasone in combination with amyloid b_25-35. Finally, melatonin decreased glucocorticoid receptor translocation into the nuclei in these cells.

Conclusion: 

The role of melatonin to avoid glucocorticoid toxicity was further demonstrated in hippocampal cells. Harmful properties of glucocorticoids during aging in brain make melatonin a physiological agent with clear beneficial properties.