Effects of ethanol on neurotrophic factors, apoptosis-related proteins, endogenous antioxidants, and reactive oxygen species in neonatal striatum: relationship to periods of vulnerability.
The developing central nervous system is extremely sensitive to ethanol, with well-defined temporal periods of vulnerability. Many brain regions are particularly susceptible to ethanol during the early neonatal period, corresponding to the human third trimester, which represents a dynamic period of growth and differentiation. For this study, neonatal rats were acutely exposed to ethanol or control conditions at a neonatal age when the developing striatum has been shown to be vulnerable to ethanol (postnatal day 3 [P3]), and at a later age (P14), when this developing region is relatively ethanol-resistant. We then analyzed basal levels of neurotrophic factors (NTFs), and ethanol-mediated changes in NTFs, apoptosis-related proteins, antioxidants, and reactive oxygen species (ROS) generation, which may underlie this differential temporal vulnerability. Sequential analyses were made following ethanol exposure on these two postnatal days, with assessments of NTFs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4); apoptosis-related proteins Bcl-2, Bcl-xl, Bax, Akt and c-jun N-terminal kinase (JNK); antioxidants superoxide dismutase, glutathione reductase and catalase; and ROS. The results indicated that basal levels of BDNF, and to some degree NGF, were greater at the older age, and that ethanol exposure at the earlier age elicited considerably more pro-apoptotic and fewer pro-survival changes than those produced at the later age. Thus, differential temporal vulnerability to ethanol in this CNS region appears to be related to differences in both differential levels of protective substances (e.g. NTFs), and differential cellular responsiveness which favors apoptosis at the most sensitive age and survival at the resistant age.
Heaton
Marieta Barrow
MB
Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Box 100244, Gainesville, FL 32610-0244, USA. heaton@ufbi.ufl.edu
Paiva
Michael
M
Madorsky
Irina
I
Mayer
Joanne
J
Moore
D Blaine
DB
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D002492:Central Nervous System Depressants; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D000431:Ethanol