Vitamin E protects against oxidative damage and learning disability after mild traumatic brain injury in rats.
BACKGROUND
Reactive oxygen species induce neuronal damage, and their role in reducing synaptic plasticity and function is beginning to be understood. Vitamin E is a potent reactive oxygen species scavenger, which has the potential to reduce oxidative damage encountered after traumatic brain injury (TBI). Brain-derived neurotrophic factor (BDNF) can facilitate synaptic function and support learning by modulating the CaMKII system, synapsin I, and cAMP-response element-binding protein (CREB). The elevation of superoxide dismutase (SOD) and Sir2 (silent information regulator 2) play an important role in resistance to oxidative stress.


OBJECTIVE
We examined the possibility that vitamin E supplemented in the diet may help counteract the effects of TBI on the molecular substrates underlying synaptic plasticity and cognitive function in the hippocampus.


METHODS
Rats were fed a regular diet with or without 500 IU/kg of vitamin E for 4 weeks (n = 6-8 per group) before a mild fluid percussion injury (FPI) was performed.


RESULTS
FPI increased protein oxidation as evidenced by elevated levels of protein carbonyls and reduced levels of SOD and Sir2. In addition, FPI resulted in poor performance in the Morris water maze, which was accompanied by reduced levels of BDNF and its downstream effectors on synaptic plasticity, synapsin I, CREB, and CaMKII. Supplementation of vitamin E in the diet counteracted all the observed effects of FPI.


CONCLUSIONS
These results suggest that vitamin E dietary supplementation can protect the brain against the effects of mild TBI on synaptic plasticity and cognition, using molecular systems associated with the maintenance of long-term plasticity, such as BDNF and Sir2.
Aiguo Wu
University of California at Los Angeles, Los Angeles, California 90095, USA.
Zhe Ying
Gomez-Pinilla
Fernando
F
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D056564:Sirtuin 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D024505:Tocopherols / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D016704:Synapsins; D013482:Superoxide Dismutase; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D024505:Tocopherols