Effects of melatonin on dexamethasone exposure induced changes in melatonin receptor of adult mouse hippocampus

Abstract

Chronic stress or prolonged exposure to high levels of glucocorticoid induces neuropathological alterations, such as dendritic atrophy of hippocampal or cortical neurons. The chronic administration of high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, impairs long-term memory, decreases neurogenesis, reduces body weight and induces mortality in mice. DEX is typically administered clinically for a prolonged period. DEX may mimic the effects of GR possession. Our previous study demonstrated that mice treated with DEX for 21 consecutive days had significantly impaired spatial memory in the Morris Water Maze task. Therefor, we were interested in studying the underlying mechanism by which chronic DEX administration induced cognitive impairment. In this study, we attempted to explore whether chronic DEX administration altered the molecular neuroplasticity related to cognitive pathway. The results showed that mice treated with DEX for 21 consecutive days had significantly reduced brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate (NMDA) receptor subunit (NR2A/B), calcium/calmodulin-dependent protein kinase II (CaMKII) and melatonin receptor (MT1) in the hippocampus. Melatonin, a hormone mainly synthesized in the pineal gland, is a potent free radical scavenger, antioxidant and antidepressant. Melatonin plays various physiological functions via the melatonin receptor (MT1). It may be interesting to explore the mechanism of melatonin especially MT1 that is associated with the role of stress as a key factor to precipitate memory impaiement. In the present study, we investigated whether melatonin could counteract the effects of chronic DEX on the molecular neuroplasticity related to cognitive via MT1. Our results showed that mice pretreated with melatonin prior to the DEX-treatment had significantly prevented a DEX-induced reduction in the expression of BDNF, NR2A/B, CaMKII, NR2A/B and MT1. This finding indicates that melatonin may play a neuroproptective role in molecular neuroplasticity related to cognition via MT1. However, the precise mechanism by which melatonin possesses anti-stress requires further in investigation