Melatonin improves cognitive dysfunction and decreases gliosis in the streptozotocin-induced rat model of sporadic Alzheimer's disease.

Introduction: Alzheimer's disease (AD) and other forms of dementia have a devastating effect on the community and healthcare system, as neurodegenerative diseases are causing disability and dependency in older population. Pharmacological treatment options are limited to symptomatic alleviation of cholinergic deficit and accelerated clearance of β-amyloid aggregates, but accessible disease-modifying interventions are needed especially in the early phase of AD. Melatonin was previously demonstrated to improve cognitive function in clinical setting and experimental studies also. Methods: In this study, the influence of melatonin supplementation was studied on behavioral parameters and morphological aspects of the hippocampus and amygdala of rats. Streptozotocin (STZ) was injected intracerebroventricularly to induce AD-like symptoms in male adult Wistar rats (n = 18) which were compared to age-matched, sham-operated animals (n = 16). Melatonin was administered once daily in a dose of 20 mg/kg body weight by oral route. Behavioral analysis included open-field, novel object recognition, and radial-arm maze tests. TNF-α and MMP-9 levels were determined from blood samples to assess the anti-inflammatory and neuroprotective effects of melatonin. Immunohistological staining of brain sections was performed using anti-NeuN, anti-IBA-1, and anti-GFAP primary antibodies to evaluate the cellular reorganization of hippocampus. Results and Discussion: The results show that after 40 days of treatment, melatonin improved the cognitive performance of STZ-induced rats and reduced the activation of microglia in both CA1 and CA3 regions of the hippocampus. STZ-injected animals had higher levels of GFAP-labeled astrocytes in the CA1 region, but melatonin treatment reduced this to that of the control group. In conclusion, melatonin may be a potential therapeutic option for treating AD-like cognitive decline and neuroinflammation.