Melatonin Improves Short-Term Spatial Memory in a Mouse Model of Alzheimer's Disease

Degener Neurol Neuromuscul Dis. 2021 May 6:11:15-27. doi: 10.2147/DNND.S291172. eCollection 2021.

Abstract

Introduction: Alzheimer's disease (AD) is a neurodegenerative disease that has become a leading cause of death in recent years. Impairments in spatial learning and memory are an important clinical feature of AD. Melatonin (MLT), the main product secreted by the pineal gland, showed multiple antioxidant, anti-inflammatory, and neuroprotective properties.

Purpose: The present study aimed to explore the possible prophylactic effects of MLT against spatial memory deficits in a sporadic mouse model of AD induced by D-galactose and aluminium chloride (AlCl3).

Methods: Four groups of mice (n = 10 per group) were prepared: control, AD (the D-galactose and AlCl3 AD model group), AD+MLT (AD mice treated with 80 mg/kg MLT), and AD+DON (AD mice treated with 3 mg/kg donepezil). We then used the object location and Y-maze tests to assess spatial memory in the four groups. Gene expression levels of brain-derived neurotrophic factor (Bdnf) and cAMP-responsive element-binding protein (Creb1) were measured using real-time polymerase chain reaction.

Results: We found that MLT improved spatial memory in the sporadic AD mice. MLT ameliorated Creb1 gene expression and significantly increased Bdnf gene expression in the hippocampus of AD model mice compared with the AD group.

Conclusion: MLT could have a substantial potential to alleviate memory impairment in sporadic AD if introduced at early stages.

Keywords: Alzheimer’s disease; BDNF; CREB; melatonin; spatial memory.

Grants and funding

King Abdulaziz University, Jeddah, Saudi Arabia.