Ethanol-induced alterations in neurotrophin expression in developing cerebellum: relationship to periods of temporal susceptibility.
BACKGROUND
The developing cerebellum has been shown to be profoundly affected by exposure to ethanol and to exhibit a temporal pattern of vulnerability. Cerebellar Purkinje cells are particularly susceptible to ethanol on postnatal day 4 or day 5 (P4-5), whereas this population is much less vulnerable to similar ethanol insult slightly later in the postnatal period (P7-9). The purpose of the study was to determine whether differential alterations in neurotrophic factors might be associated with this differential susceptibility.


METHODS
Neonatal rats were exposed to ethanol via vapor inhalation, and enzyme-linked immunoabsorbent assays were subsequently conducted to assess cerebellar nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 protein content. These analyses were made after ethanol exposure during the period of maximal cerebellar ethanol sensitivity (postnatal days 4-5 [P4-51), during a period of much lower sensitivity (P7-8), and during the entire "brain growth spurt" (P4-10).


RESULTS
These determinations revealed a significant ethanol-induced decrease in cerebellar nerve growth factor after exposure on P4-5 but not after exposure on P7-8 or P4-10. No significant changes in brain-derived neurotrophic factor or neurotrophin-3 were found with any of the exposure paradigms.


CONCLUSIONS
These results suggest that alterations in nerve growth factor, which has previously been shown to support cerebellar Purkinje and granule cells, may be a mechanism contributing to the early ethanol susceptibility within these neuronar populations.
Heaton
M B
MB
University of Florida Brain Institute, Department of Neuroscience, Center for Alcohol Research, Gainesville, USA. heaton@ufbi.ufl.edu
Mitchell
J J
JJ
Paiva
M
M
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000097:blood; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D008297:Male; D020932:Nerve Growth Factor / Q000187:drug effects* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3 / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans
D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D000431:Ethanol; D020932:Nerve Growth Factor