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Melatonin suppresses astrocyte reactivity and Mitigates cognitive deficits induced by a high-carbohydrate, high-fat
Davood Dorranipour1, Iman Zangiabadi2, Mostafa Peyvandi3
1Department of Surgical Technology, Ferdows Faculty of Medical Sciences, Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Background:
High-carbohydrate and high-fat (HCHF) diets may impair cognitive function through neuroinflammation, oxidative stress, and astrocyte activation. This study investigated the effects of melatonin on memory impairment and astrocyte reactivity in rats with diet-induced metabolic syndrome.
Methods And Results:
Adult male Wistar rats were fed an HCHF diet for eight weeks, followed by daily oral melatonin treatment (5, 10, or 30 mg/kg) for four weeks while continuing the diet. Working memory was assessed using the Y-maze spontaneous alternation test. Hippocampal and hypothalamic tissues were evaluated for proinflammatory cytokines, oxidative stress markers, and glial fibrillary acidic protein (GFAP) immunoreactivity. HCHF feeding caused weight gain, dyslipidemia, glucose intolerance, impaired working memory, increased neuroinflammation and oxidative damage, and astrogliosis in both brain regions. Melatonin did not improve glucose tolerance or lipid profiles at any dose. However, working memory performance in melatonin-treated rats was comparable to that of controls at all doses. Melatonin also reduced GFAP-positive astrocytes, proinflammatory cytokine levels, and lipid peroxidation, while increasing superoxide dismutase activity. These effects were mainly dose-dependent in the hippocampus, whereas memory improvement showed no clear dose-dependent pattern.
Conclusions:
Melatonin improved working memory and reduced astrocyte reactivity, neuroinflammation, and oxidative stress in rats fed an HCHF diet, without improving systemic metabolic abnormalities. These findings suggest that melatonin may protect against diet-induced brain injury through mechanisms related to astrocyte activation, inflammation, and oxidative stress.
