Aims: This study was aimed to determine whether ethanol exposure during early development altered neurogenesis in the brain of adult rats. Methods: Pregnant rats were given either ethanol-mixed or mannose-mixed (for control) rodent liquid diet ad libitum. Ethanol drinking continued during pregnancy and nursing. After weaning, the pups (ACo: pups from control mothers, AEo: pups from ethanol exposed mothers) received normal diet and water ad libitum for 11 weeks. Then the rats were anesthetized, their brains were collected and the hippocampal samples were processed for isolation of neural progenitor cells (NPCs). ACo NPCs and AEo NPCs were sequentially grown in media containing different growth factors that induced proliferation and differentiation. Results and Conclusions: Neuronal maturation was significantly delayed in ethanol-exposed rats. ACo NPCs, up to day 7 of culture, exhibited high β-catenin-probe binding, an increase in Ca2+1 when exposed to γ-amino butyric acid (GABA) and lack of response to glutamate (Glu) exposure. β-Catenin-probe binding and the stimulatory effects of GABA declined thereafter. ACo NPCs, at culture day 29, exhibited high β-catenin-probe binding, lack of response to GABA and elevated Glu-induced increase in Ca2+i. Cultures of AEo NPCs showed an amplified stimulatory effects of GABA, attenuated stimulatory effects of Glu and attenuated the delayed (culture day 29) increase in the expression of Wnt proteins and β-catenin-probe binding. This suggests a significant alteration in neurogenesis and synapse formation in adult rats exposed to ethanol at early development through their alcohol-drinking mothers.
Bibliographical noteFunding Information:
Acknowledgements — This project is partially funded by a grant from the Graduate School of the University of Minnesota.