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Protection of the Developing Brain with Anthocyanins Against Ethanol-Induced Oxidative Stress and Neurodegeneration

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Abstract

Oxidative stress has been implicated in the pathophysiology of several neurodegenerative disorders. Numerous studies have reported that ethanol exposure produces reactive oxygen species (ROS), one of the best-known molecular mechanisms of ethanol neurotoxicity. We recently reported gamma-aminobutyric acid B1 receptor (GABAB1R)-dependent protection by anthocyanins against ethanol-induced apoptosis in prenatal hippocampal neurons. Here, we examined the effect of anthocyanin neuroprotection against ethanol in the hippocampus of the postnatal day-7 rat brain. After 4 h of ethanol administration, either alone or together with anthocyanin, the expression of glutamate receptors (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs)), intracellular signaling molecules, and various synaptic, inflammatory, and apoptotic markers was evaluated. The results suggest that anthocyanins significantly reversed the ethanol-induced inhibition of glutamatergic neurotransmission, synaptic dysfunction, GABAB1R activation, and neuronal apoptosis by stimulating the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/v-akt murine thymoma viral oncogene (Akt)/glycogen synthase kinase 3 beta (GSK3β) pathway in the hippocampus of postnatal rat brain. Anthocyanins also inhibited the ethanol-activated expression of phosphorylated c-Jun N terminal kinase (p-JNK), phospho-nuclear factor kappa B (p-NF-κB), cyclooxygenase 2 (COX-2), as well as attenuating neuronal apoptosis in the hippocampal CA1, CA3 and DG regions of the developing rat brain. Furthermore, anthocyanins increased cell viability, attenuated ethanol-induced PI3K-dependent ROS production, cytotoxicity, and caspase-3/7 activation in vitro. In conclusion, these results suggest that anthocyanins are beneficial against ethanol abuse during brain development.

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Acknowledgments

This research was supported by the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (2012-0009521).

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Biology and Applied Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, 660-701, Republic of Korea

    Shahid Ali Shah, Gwang Ho Yoon & Myeong Ok Kim

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  1. Shahid Ali Shah
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  2. Gwang Ho Yoon
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  3. Myeong Ok Kim
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Correspondence to Myeong Ok Kim.

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Shah, S.A., Yoon, G.H. & Kim, M.O. Protection of the Developing Brain with Anthocyanins Against Ethanol-Induced Oxidative Stress and Neurodegeneration. Mol Neurobiol 51, 1278–1291 (2015). https://doi.org/10.1007/s12035-014-8805-7

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  • DOI: https://doi.org/10.1007/s12035-014-8805-7

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