Ethanol effects on neonatal rat cortex: comparative analyses of neurotrophic factors, apoptosis-related proteins, and oxidative processes during vulnerable and resistant periods.
The developing central nervous system (CNS) is highly susceptible to ethanol, with acute or chronic exposure producing an array of anomalies and cell loss. Certain periods of vulnerability have been defined for various CNS regions, and are often followed by periods of relative ethanol resistance. In the present study, neonatal rats were acutely exposed to ethanol during a time when peak cell death is found in developing cerebral cortex (postnatal day 7; P7), and during a later neonatal period of ethanol resistance (P21). Comparisons at the two ages were made of basal levels of neurotrophic factors (NTFs), and in addition, ethanol-mediated changes in NTFs, apoptosis-related proteins, antioxidant activities, and generation of reactive oxygen species (ROS) were quantified at 0, 2, and 12 h following termination of exposure. It was found that at P21, basal levels of NTF nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were considerably higher than at P7, possibly affording protection against ethanol neurotoxicity at this age. Following ethanol treatment at P7, approximately equal numbers of pro-apoptotic and pro-survival changes were produced, although most of the pro-apoptotic alterations occurred rapidly following termination of treatment, a critical period for initiation of apoptosis. At P21, however, the large majority of ethanol-mediated changes were adaptive, favoring survival. We speculate that the capacity of the older CNS to upregulate a number of protective elements within the cellular milieu serves to greatly mitigate ethanol neurotoxicity, while in younger animals, such adjustments are minimal, thus enhancing ethanol vulnerability within this developing region.
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
Shaw
Gerry
G
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004351:Drug Resistance / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019254:Genes, bcl-2 / Q000187:drug effects / Q000235:genetics; D008297:Male; D009414:Nerve Growth Factors / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000431:Ethanol