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.
Hwang
Dong-Woo
DW
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.
Givens
Bennet
B
Nishijima
Ichiko
I
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