Ethanol-induced developmental neurodegeneration in secretin receptor-deficient mice.

Alcohol exposure during brain development induces neuronal cell death in the brain. Several neuroactive peptides have been shown to protect against alcohol-induced cell death. Secretin is a peptide hormone, and the secretin receptor is expressed in the gut and the brain. To explore a potential role of secretin signal against ethanol neurotoxicity during brain development, secretin receptor-deficient mice were exposed to ethanol on postnatal day 4. We identified significant ethanol-induced apoptosis in the external granular layer of the secretin receptor-deficient cerebellum and in the striatum after ethanol treatment. During the early postnatal period, there is a proliferation of granular cell progenitors that reside in the external granular layer. The results suggest that secretin signal plays a neuroprotective role of neuronal progenitor cells against the neurotoxicity of ethanol.