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Antioxidant Pretreatment Does Not Ameliorate Alcohol‐Induced Purkinje Cell Loss in the Developing Rat Cerebellum
Author(s) -
Grisel Jedidiah J.,
Chen WeiJung A.
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000171932.13148.cf
Subject(s) - purkinje cell , melatonin , cerebellum , oxidative stress , cerebellar vermis , alcohol , antioxidant , medicine , endocrinology , stereology , cell damage , chemistry , biochemistry
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.