Overexpression of NGF ameliorates ethanol neurotoxicity in the developing cerebellum.
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.
Heaton
M B
MB
McKnight Brain Institute, 100 S. Newell Drive, Gainesville, Florida 32610-0244, USA. heaton@ufbi.ufl.edu
Mitchell
J J
JJ
Paiva
M
M
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
D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D000431:Ethanol; D020932:Nerve Growth Factor