Astrocyte response to melatonin treatment in rats under high-carbohydrate high-fat diet.

The involvement of consumption of high-carbohydrate high-fat (HCHF) diet in cognitive impairment is attributed, at least in part, to the activation of astrocytes, which contributes to the development of neuroinflammation, oxidative stress, and subsequent cognitive deficits. This study aimed to assess the influence of melatonin on cognitive impairment and astrogliosis induced by the HCHF diet in rats. Male Wistar rats were fed an HCHF diet for eight weeks to induce obesity and metabolic syndrome. Subsequently, they received oral melatonin treatment for four weeks at doses of 5 mg/kg, 10 mg/kg, and 30 mg/kg, alongside the HCHF diet. Cognitive function was evaluated using the Y-maze test, while the levels of proinflammatory cytokines, oxidative stress, and the number glial fibrillary acidic protein (GFAP) positive cells were assessed in the hippocampi and hypothalamus. The consumption of the HCHF diet resulted in weight gain, hyperlipidemia, impaired glucose tolerance, cognitive decline, neuroinflammation, oxidative stress damage, and astrogliosis in rats. Although melatonin treatment did not demonstrate beneficial effects on blood glucose and lipid metabolism, it improved the impaired working memory caused by the HCHF diet. Melatonin exhibited a dose-dependent reduction of astrogliosis, neuroinflammation, and lipid peroxidation while restored superoxide dismutase in the hippocampus and hypothalamus of HCHF diet-treated rats. These findings provide evidence that melatonin inhibits astrocyte activation, thereby attenuating inflammation and minimizing oxidative stress damage induced by the HCHF diet.