The neuroprotective and antiapoptotic effects of melatonin in cerebellar neurons involve glucocorticoid receptor and p130 signal pathways

Melatonin is an endocrine factor known to affect a number of physiological functions. The present studies have demonstrated an additional activity for pineal melatonin. specifically associated with the survival and differentiation of neuroblasts. Based on experimental data several conclusions might be drawn. First, melatonin negatively regulates the expression of glucocorticoid receptor (GR) in cerebellar granule neurons. Second. downregulation of GR is associated with a marked decrease in programmed cell death of the granule neurons. Third, melatonin upregulates the expression of p130, which is an essential factor for the initiation and maintenance of neuronal development and differentiation. Thus, melatonin function in postmitotic neurons involves several regulatory pathways with partially overlapping roles. The biological implications are discussed in light of these results. (C) 2001 Elsevier Science Ltd. All rights reserved.