期刊
NEUROCHEMISTRY INTERNATIONAL
卷 61, 期 3, 页码 310-320出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2012.05.010
关键词
Alcohol; Apoptosis; Caspase 3; Cognitive deficits; Fetal alcohol spectrum disorders (FASDs); Neuroinflammation; Nuclear factor kappa beta (NF kappa beta); Oxidative stress; Tocotrienol
资金
- Indian Council of Medical Research
Ethanol-induced damage in the developing brain may result in cognitive impairment including deficits on neuropsychological tests of learning, memory and executive function, yet the underlying mechanisms remain elusive. In the present study we investigated the protective effect of tocotrienol against cognitive deficit, neuroinflammation and neuronal apoptosis in rat pups postnatally exposed to ethanol. Pups were administered ethanol (5 g/kg, 12% v/v) by intragastric intubation on postnatal days 7, 8 and 9. Ethanol-exposed pups showed significant memory impairment in Morris water maze task as evident from increase in escape latency and total distance travelled to reach the hidden platform. Time spent in target quadrant, % total distance traversed in target quadrant and frequency of appearance in target quadrant was also significantly decreased in ethanol exposed pups in probe trial. Poor memory retention was exhibited by ethanol-exposed pups in elevated plus maze test also. Impaired cognition was associated with significantly enhanced acetylcholinesterase activity, increased neuroinflammation (oxidative-nitrosative stress, TNF-alpha, IL-1 beta and TGF-beta 1) and neuronal apoptosis (NF-kappa beta and Caspase-3) in different brain regions of ethanol-exposed pups. Co-administration with tocotrienol significantly ameliorated all the behavioral, biochemical and molecular alterations in the different brain regions of ethanol exposed pups. The current study thus demonstrates the possible involvement of NF-kappa B mediated apoptotic signaling in cognitive deficits associated with postnatal ethanol exposure in rats and points to the potential of tocotrienol in the prevention of cognitive deficits in children with fetal alcohol spectrum disorders (FASDs). (c) 2012 Elsevier Ltd. All rights reserved.
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