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Nesfatin-1 Ameliorate Learning and Memory Deficit via Inhibiting Apoptosis and Neuroinflammation Following Ethanol-Induced Neurotoxicity in Early Postnatal Rats

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Abstract

Fetal exposure to alcohol can cause a wide range of long-lasting physiological and behavioral effects, collectively referred to as fetal alcohol spectrum disorders (FASD). Neurocognitive disorders caused by alcohol in children are linked to activation of oxidative-inflammatory cascade and a high level of apoptotic neurodegeneration in several brain regions, such as hippocampus. NCB2/nesfatin-1 is a novel identified anorexigenic peptide. In addition recently, it has been reported as anti-apoptotic and anti-inflammatory properties of nesfatin-1 under both in vitro and in vivo situations. This research aimed at evaluating the protective activities of nesfatin-1 on ethanol-induced neuroinflammation and neuronal apoptosis in rat hippocampus with postnatal alcohol exposure. Administration of 5.27 g/kg of ethanol in milk solution 27.8 mL/kg to male rat pups was performed through intragastric intubation on postnatal days 2–10. The pups were administered 5 and 10 µg/kg of nesfatin-1 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 GFAP and apoptotic cell death was detected by TUNEL staining, also ELISA assay was done for measuring TNF-α, and antioxidant enzymes levels. Nesfatin-1 treatment could significantly improve spatial memory impairment (P < 0.01). Also it could significantly increase the activity of total SOD and GSH-Px (P < 0.05). Nesfatin-1 treatment caused a decrease in TNF-α and MDA levels, than the ethanol group (P < 0.01). Also it reduced the hippocampal apoptotic cells death, and GFAP-positive cells (P < 0.01). Based on the findings, apoptotic signaling mediated by the oxidative-inflammatory cascade is inhibited by nesfatin-1 in rat pups with ethanol exposure in the postnatal period.

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Authors and Affiliations

  1. Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

    Fatemeh Ghamari, Golamhassan Vaezi & Vida Hojati

  2. Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Mehdi Khaksari

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  1. Fatemeh Ghamari
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  2. Golamhassan Vaezi
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  3. Mehdi Khaksari
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  4. Vida Hojati
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Correspondence to Mehdi Khaksari.

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Ghamari, F., Vaezi, G., Khaksari, M. et al. Nesfatin-1 Ameliorate Learning and Memory Deficit via Inhibiting Apoptosis and Neuroinflammation Following Ethanol-Induced Neurotoxicity in Early Postnatal Rats. Int J Pept Res Ther 26, 2029–2038 (2020). https://doi.org/10.1007/s10989-019-09999-w

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