Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury.
Traumatic brain injury is a well-recognized environmental risk factor for developing Alzheimer's disease. Repetitive concussive brain injury (RCBI) exacerbates brain lipid peroxidation, accelerates amyloid (Abeta) formation and deposition, as well as cognitive impairments in Tg2576 mice. This study evaluated the effects of vitamin E on these four parameters in Tg2576 mice following RCBI. Eleven-month-old mice were randomized to receive either regular chow or chow-supplemented with vitamin E for 4 weeks, and subjected to RCBI (two injuries, 24 h apart) using a modified controlled cortical impact model of closed head injury. The same dietary regimens were maintained up to 8 weeks post-injury, when the animals were killed for biochemical and immunohistochemical analyses after behavioral evaluation. Vitamin E-treated animals showed a significant increase in brain vitamin E levels and a significant decrease in brain lipid peroxidation levels. After RBCI, compared with the group on regular chow, animals receiving vitamin E did not show the increase in Abeta peptides, and had a significant attenuation of learning deficits. This study suggests that the exacerbation of brain oxidative stress following RCBI plays a mechanistic role in accelerating Alphabeta accumulation and behavioral impairments in the Tg2576 mice.
Conte
Valeria
V
Head Injury Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Uryu
Kunihiro
K
Fujimoto
Scott
S
Yao
Yuemang
Y
Rokach
Joshua
J
Longhi
Luca
L
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
McIntosh
Tracy K
TK
Praticò
Domenico
D
D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry; D001924:Brain Concussion / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology*
C115626:8,12-iso-isoprostane F2alpha-VI; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D014810:Vitamin E; D015237:Dinoprost