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It has been shown that alcohol consumption by pregnant women can have detrimental effects on the developing fetus and lead to fetal alcohol spectrum disorders (FASD). Exposure to alcohol in rat pups during this period causes long-term changes in the structure of the animal's hippocampus, leading to impaired hippocampal-related brain functions such as navigation tasks and spatial memory. Apelin-13, a principal neuropeptide with inhibitory effects on neuroinflammation and brain oxidative stress production, has beneficial properties on memory impairment and neuronal injury. The protective effects of apelin-13 have been evaluated on ethanol-related neurotoxicity in the hippocampus of rat pups. Rat pups from 2 until 10 postnatal day, similar to the third trimester of pregnancy in humans, were intubated total daily dose of ethanol (5/27 g/kg/day). Immediately after intubation, 25 and 50 μg/ kg of apelin-13 was injected subcutaneously. By using Morris water maze task, the hippocampus- dependent memory and spatial learning were evaluated 36 days after birth. Then, Immunohistochemical staining was done to determine the levels of GFAP and caspase-3. ELISA assay was also performed to measure both TNF-α and antioxidant enzymes levels. The current study demonstrates that administration of apelin-13 attenuates spatial memory impairment significantly (P < 0.001). After ethanol neurotoxicity, apelin-13 could also increase the catalase level (P < 0.001), activity of total superoxide dismutase as well as glutathione concentration noticeably (P < 0.05). Other impacts of it could be mentioned as attenuating TNF-α production and also preventing lipid peroxidation (P < 0.001). In addition, the results showed that the level of GFAP as a neuroinflammation factor and the number of active caspase-3 positive cells can be decreased by apelin-13 (P < 0.01). Regarding the protective effects of apelin-13 against ethanol-induced neurotoxicity, it is a promising therapeutic choice for FASD; but more studies are needed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Fetal alcohol spectrum disorder (FASD), which is caused by prenatal alcohol exposure, can result in cell death in specific brain regions. Alcohol-induced neurocognitive defects offspring's are included with activation of oxidative-inflammatory cascade followed with wide apoptotic neurodegeneration in many brain's regions such as hippocampus. According to the latest studies, H 2 S (hydrogen sulfide) can protect neuronal cells via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms in different animal models. Therefore, we aimed to evaluate the protective effects of H 2 S on ethanol-induced neuroinflammation and neuronal apoptosis in pup hippocampus with postnatal alcohol exposure. Administration of ethanol (5.27 g/kg) in milk solution (27.8 mL/kg) for each rat pups was performed through intragastric intubation on 2 to 10 postnatal days and NaHS as H 2 S donor (1 mg/kg) was injected on similar time, subcutaneously. For examining the antioxidant and anti-inflammatory effects, ELISA assay was performed to determine the levels of TNF-α, IL1β, and antioxidant enzymes. Immunohistochemical staining was performed to evaluate the expression levels of GFAP and caspase-3 also Nissl staining was done for necrotic cell death evaluation. H 2 S treatment could significantly increase the activity of total superoxide dismutase, catalase, and glutathione (P < 0.05). It also decreased the levels of TNF-α, IL1β, and malondialdehyde, compared with the ethanol group (P < 0.05). Moreover, the number of hippocampal caspase-3, GFAP-positive cells, and necrotic cells death reduced in the H 2 S group (P < 0.01). Based on the findings, H 2 S can inhibit apoptotic signaling that is mediated by the oxidative-inflammatory cascade following ethanol exposure of rat pups on postnatal period.

According to experimental and clinical findings, fetal brain development may be interrupted by maternal alcohol consumption during pregnancy. Adult hippocampal neurogenesis is thought to play a role in cognition function (i.e. learning and memory). Recent evidence suggests that ethanol administration causes major apoptotic neurodegeneration in many regions of the rats' developing brain during the synaptogenesis period. Based on the recent studies, H 2 S improve learning and memory via increased neurogenesis and antiapoptotic mechanisms in different animal models. In this study, we aimed to evaluate the protective effects of hydrogen sulfide on alcohol-induced memory impairment, hippocampus neurogenesis and neuronal apoptosis in rat pups with postnatal ethanol exposure. Administration of ethanol to male rat pups was performed through intragastric intubation on postnatal days 2-10. The pups were administered 1 mg/kg of NaHS (H 2 S donor) on postnatal days 2-10. For examining the spatial memory, Morris water maze test was carried out 36 days after birth. Following the behavioral test, immunohistochemical staining was performed to evaluate the expression levels of BrdU, BDNF and Apoptotic cell death was detected by TUNEL staining. Hydrogen sulfide (H 2 S) treatment could significantly improve spatial memory impairment (P < 0.05) and significantly increase the expression of BrdU and BDNF in dentate gyrus area (P < 0.05). It also decreased positive TUNEL cells, compared with the ethanol group (P < 0.01). Based on the findings, H 2 S makes significant neuroprotective effects on Ethanol neurotoxicity due to its neurogenesis and anti-apoptotic activity., (Copyright © 2019 Elsevier Inc. All rights reserved.)