Astaxanthin reverses neurodevelopmental impairment by decreasing oxidative stress-induced disruption of Maf/Bcl2 signaling in prenatal alcohol exposure.

Background: Prenatal alcohol exposure (PAE) is recognized as the leading cause of adverse prenatal exposure disorders worldwide. The neurodevelopmental impairments resulting from PAE in offspring are classified under fetal alcohol syndrome (FAS). Nonetheless, the precise underlying pathogenic mechanisms of FAS remain incompletely understood, and effective therapeutic interventions are currently lacking. Notably, the antioxidant astaxanthin has demonstrated significant neuroprotective properties.

Methods: In this study, we established a C57BL/6J mouse model of FAS and administered potential therapeutic doses of astaxanthin through oral gavage. We evaluated the dual effects of ethanol exposure and astaxanthin intervention on oxidative stress, cognitive development, and cellular apoptosis in FAS. Furthermore, using molecular detection and plasmid transfection, we validated the regulatory cascade between the transcription factor Maf and the antiapoptotic protein B-cell lymphoma 2 (Bcl2), demonstrating the therapeutic efficacy and mechanism of astaxanthin against FAS.

Results: The results demonstrate that prenatal alcohol exposure induces neuronal oxidative damage and cognitive developmental impairments, concomitant with reduced expression of the transcription factor Maf in the brain and consequent suppression of antiapoptotic Bcl2 activity. Strikingly, astaxanthin administration significantly attenuated alcohol-induced reactive oxygen species accumulation and restored both Maf and Bcl2 expression levels. This intervention effectively ameliorated neuronal apoptosis and neurodevelopmental abnormalities.

Conclusion: These findings reveal that astaxanthin alleviates FAS-related pathophysiology by rescuing the alcohol-disrupted Maf-Bcl2 axis, consequently reducing neuronal cell death. This study provides novel mechanistic insights into FAS pathogenesis and identifies a promising therapeutic strategy.