In vitro study of the long-term cortisol treatment effects on the growth rate and proliferation of the neural stem/precursor cells

Adult neural stem/precursor cells (NSPCs) residing in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus are involved in the memory formations and psychological problems. It is believed that basal levels of glucocorticoids are essential for neuronal development, plasticity, and survival, while stress-mediated levels of glucocorticoids produce neuronal loss. Degeneration of NSPCs by the apoptotic and necrotic stimuli have great devastating outcomes on the brain and contributes to the pathophysiology of neurological as well as psychological disorders. Using MTT assay, acridine orange, and TUNEL assay, we have demonstrated that cortisol at high and excessive (more than 5 mu M) levels had anti-proliferative effects on the NSPCs derived from subventricular and subgranular zones in a dose-and time-dependent manner through apoptosis as well as necrosis. These outcomes can highlight the role of stress-mediated decline of adult neurogenesis in the aging brain and interconnect stress-mediated cortisol secretion with brain aging diseases.