Antioxidant pretreatment does not ameliorate alcohol-induced Purkinje cell loss in the developing rat cerebellum.
BACKGROUND
Recent research has suggested that oxidative stress is a potential mechanism for alcohol-induced injury and that supplementation with antioxidants can ameliorate alcohol-induced damage. In this study, two known antioxidants, melatonin and U83836E, were assessed for their effectiveness in blocking the expected alcohol-induced cerebellar Purkinje cell loss in neonatal rat pups.


METHODS
Sprague-Dawley rat pups were artificially reared from postnatal days (PDs) 4-9 and were exposed to either alcohol or antioxidants (melatonin or U83836E) individually or in combination. A normal control group (raised by rat dams) was included in this study. On PD 9, the brain from each pup was removed and weighed, and the cerebellar vermis was processed for stereological cell counting.


RESULTS
Alcohol exposure during the brain growth spurt produced microencephaly, in addition to significant decreases in the number and density of Purkinje cells in lobule I and the volume of lobule I. The antioxidants did not reduce any of the adverse effects observed from alcohol exposure, and they did not decrease the Purkinje cell number when administered alone. Furthermore, antioxidants did not change the only blood alcohol concentration measured on PD 6.


CONCLUSIONS
The results confirmed alcohol-induced microencephaly and cerebellar Purkinje cell loss from neonatal alcohol exposure, and they showed that neither antioxidant could attenuate these adverse effects on the developing brain. The inability of antioxidants to reduce Purkinje cell loss from neonatal alcohol exposure suggests the existence of alternative mechanisms for developmental alcohol-induced Purkinje cell loss.
Grisel
Jedidiah J
JJ
Department of Human Anatomy and Medical Neurobiology, College of Medicine, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA.
Chen
Wei-Jung A
WJ
D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002531:Cerebellum / Q000473:pathology*; D002839:Chromans / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D011292:Premedication; D011689:Purkinje Cells / Q000473:pathology*; D051381:Rats
D000975:Antioxidants; D002839:Chromans; D010879:Piperazines; C066382:U 78517F; D000431:Ethanol; D008550:Melatonin