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 4h 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.