title: Protection of the developing brain with anthocyanins against ethanol-induced oxidative stress and neurodegeneration.
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.
authors.affiliation: Department of Biology and Applied Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Shahid Ali
authors.initials: SA
authors.lastname: Shah
authors.forename: Gwang Ho
authors.initials: GH
authors.lastname: Yoon
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000872:Anthocyanins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D000431:Ethanol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; C492973:alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor, human; D000431:Ethanol; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid