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  • Title: Obestatin improve spatial memory impairment in a rat model of fetal alcohol spectrum disorders via inhibiting apoptosis and neuroinflammation.
    Author: Toosi A, Shajiee H, Khaksari M, Vaezi G, Hojati V.
    Journal: Neuropeptides; 2019 Apr; 74():88-94. PubMed ID: 30642580.
    Abstract:
    Clinical and experimental evidence have demonstrated that, use of alcohol during pregnancy can interrupt brain development. Alcohol-induced neurocognitive deficits in offspring's are involved with activation of oxidative-inflammatory cascade joined with extensive apoptotic neurodegeneration in different brain regions such as hippocampus. Obestatin is a newly discovered peptide with anti-inflammatory, antioxidant, activities in different animal models. In this study, we aimed to evaluate the protective effects of obestatin on alcohol-induced neuronal apoptosis and neuroinflammation in rat pups with postnatal ethanol exposure. Through intragastric intubation, ethanol (5/27 g/kg/day) was administered in male Wistar rat pups on postnatal days 2-10 (third trimester in humans). The animals received Obestatin (1 and 5 μg/kg, S.C.) on postnatal days 2-10. Thirty-six days after birth, the spatial memory test was performed using Morris water maze test, and then, antioxidant enzymes and TNF-α levels were measured by ELISA assay. The expression level of GFAP and caspase-3 proteins was determined via immunohistochemical staining after the behavioral test. Obestatin significantly improved spatial memory deficits (P < .01), and obestatin treatment could significantly increase glutathione and total superoxide dismutase activity (P < .05), reduce level of malondialdehyde (P < .05) and TNF-α in comparison with the ethanol group (P < .01). It's also reduced caspase-3 level, and decreased GFAP-positive cells in the hippocampus of ethanol-exposed rat pups (P < .01). The result of this study shows the potential involvement of oxidative-inflammatory cascade-mediated apoptotic signaling in cognitive deficits due to postnatal ethanol exposure, the results also indicated the neuroprotective effects of Obestatin on alcohol-related behavioral, biochemical and molecular deficits.
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