期刊
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
卷 29, 期 1, 页码 117-129出版社
WILEY
DOI: 10.1097/01.ALC.0000150004.53870.E1
关键词
fetal alcohol syndrome; antioxidants; eyeblink conditioning; cerebellum; caspase-3
资金
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [U01AA014829, T32AA007462, R01AA011945] Funding Source: NIH RePORTER
- NIAAA NIH HHS [U01 AA14829, R01 AA11945, T32 AA07462] Funding Source: Medline
Background: Rodent studies have shown that heavy binge-like ethanol (EtOH) exposure during the brain growth spurt [postnatal days (PD) 4-9] causes cerebellar neuronal loss and deficits in cerebellar-mediated eyeblink classical conditioning (ECC). Oxidative stress has been implicated in EtOH-mediated brain damage, and studies using vitamin E have reported amelioration of EtOH-induced tissue damage, including protection in rats against EtOH-induced cerebellar Purkinje cell (PC) loss on PD 4 to 5. The purpose of this study was to determine whether dietary supplementation with vitamin E concurrent with binge EtOH exposure on PD 4 to 9 in rats would attenuate the cerebellar cell death and ECC deficits. Methods: Rat pups were given one of five different neonatal treatments: (1) intubation with EtOH in milk formula (twice daily, total dose 5.25 g/kg/day), (2) intubation with EtOH in milk formula supplemented with vitamin E (12.26 mg/kg/feeding), (3) intubation with milk formula that contained vitamin E only, (4) sham intubations, or (5) normally reared unintubated controls. Between PD 26 and 33, subjects received short-delay ECC for 3 consecutive days. Unbiased stereological cell counts were performed on cerebellar PCs of left cerebellar lobules I to VI and neurons of the interpositus nucleus. In a separate study with PD 4 pups, the effects of vitamin E on EtOH-induced expression of caspase-3 active subunits were assessed using Western blot analysis. Results: EtOH-treated groups showed significant deficits in acquisition of conditioned eyeblink responses and reductions in cerebellar PCs and interpositus nucleus neurons compared with controls. Vitamin E supplementation failed to protect against these deficits. Vitamin E also failed to protect against increases in caspase-3 active subunit expression induced by acute binge EtOH exposure on PD 4. Conclusions: In contrast to the previously reported neuroprotective potential of antioxidants on EtOH-mediated cerebellar damage, vitamin E supplementation did not diminish EtOH-induced structural and functional damage to the cerebellum in this model of binge EtOH exposure during the brain growth spurt in rats.
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