title: Overexpression of NGF ameliorates ethanol neurotoxicity in the developing cerebellum.
abstract: Transgenic mice overexpressing NGF in the central nervous system under the control of the glial fibrillary acidic protein (GFAP) promoter were exposed to ethanol via vapor inhalation on postnatal days 4 and 5 (P4-5), the period of maximal cerebellar Purkinje cell sensitivity to ethanol. Wild-type controls were exposed in a similar manner. There were no differences in body weight or size following these procedures, but the transgenic brain weights at this age were significantly greater than wild-type controls. In the wild-type animals, a significant 33.3% ethanol-mediated loss of Purkinje cells in lobule I was detected via unbiased three-dimensional stereological counting on P5. In the GFAP-NGF transgenic animals, however, the 17.6% difference in Purkinje cell number in control and ethanol-exposed animals was not significant. There was a similar difference in Purkinje cell density in both groups, which did reach statistical significance (-32.7% in wild-type ethanol-treated animals, -17% in transgenic ethanol-exposed animals). These results suggest that endogenous overexpression of neurotrophic factors, which have previously been shown to protect against ethanol neurotoxicity in culture, can serve a similar protective function in the intact animal.
authors.affiliation: McKnight Brain Institute, 100 S. Newell Drive, Gainesville, Florida 32610-0244, USA. heaton@ufbi.ufl.edu
authors.forename: M B
authors.initials: MB
authors.lastname: Heaton
authors.forename: J J
authors.initials: JJ
authors.lastname: Mitchell
authors.forename: M
authors.initials: M
authors.lastname: Paiva
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D000431:Ethanol; D020932:Nerve Growth Factor