Melatonin is an endogenous antioxidant and free radical scavenger that regulates sleep/wake cycle and circadian rhythm. Previous studies indicated that melatonin is decreased during the aging process and that patients with AD have a significant reduction of this hormone. However, melatonin supplementation has been found to reduce Αβ neurotoxicity and formation while improving cognitive performance. In this study, the long-term influence of melatonin on behavior and neuropathologic changes were evaluated, after 24 weeks of 10 mg/kg melatonin treatment in the 5xFAD mice model. The 5xFAD is a transgenic mouse model for Alzheimer’s disease that mimics the accumulation of senile plaques, neuronal apoptosis and memory impairment. Overall, transgenic mice showed decreased anxiety, impaired learning, and significant increased in plaque load, replicating previous results with this strain. Melatonin improved learning in transgenic mice by decreasing distance travelled in the Morris water maze and slightly decreasing concentration in the hippocampus of 5xFAD mice compared with untreated 5xFAD. These results supported the hypothesis that long-term melatonin supplementation may be beneficial at early stages of the disease process. Early melatonin interventions may be one of the most promising strategies in the development of approaches to retard or prevent Aβ and memory deficits during this stage of the disease. In sharp contrast to conventional antioxidants, melatonin crosses the blood-brain barrier, is relatively devoid of toxicity, and constitutes a potential therapeutic candidate in AD treatment, perhaps due to improving sleep quality and clearance of plaque by increasing glymphatic system efficiency.


Stavnezer, Amy Jo



Publication Date


Degree Granted

Bachelor of Arts

Document Type

Senior Independent Study Thesis


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