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.
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University, Columbus, Ohio 43205, USA.
Dong-Woo
DW
Hwang
Bennet
B
Givens
Ichiko
I
Nishijima
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D012633:Secretin / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
D002492:Central Nervous System Depressants; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin; D000431:Ethanol