Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury
| Autor: | Luca Longhi, Yuemang Yao, Domenico Praticò, Kunihiro Uryu, Joshua Rokach, Virginia M.-Y. Lee, John Q. Trojanowski, Tracy K. McIntosh, Valeria Conte, Scott Fujimoto |
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| Rok vydání: | 2004 |
| Předmět: |
Vitamin
medicine.medical_specialty Pathology Amyloid Traumatic brain injury medicine.medical_treatment Central nervous system Enzyme-Linked Immunosorbent Assay Mice Transgenic Motor Activity medicine.disease_cause Dinoprost Biochemistry Antioxidants Lesion chemistry.chemical_compound Cellular and Molecular Neuroscience Mice Internal medicine medicine Animals Vitamin E Neurochemistry ARTICLE Brain Concussion Brain Chemistry Amyloid beta-Peptides business.industry Amyloidosis Brain Cognition medicine.disease Peptide Fragments Disease Models Animal Oxidative Stress Endocrinology medicine.anatomical_structure chemistry Closed head injury Dietary Supplements Female Alzheimer's disease medicine.symptom business Cognition Disorders Neuroscience Oxidative stress |
| Zdroj: | Journal of neurochemistry. 90(3) |
| ISSN: | 0022-3042 |
| Popis: | Traumatic brain injury (TBI) increases susceptibility to Alzheimer's disease (AD), but it is not known how TBI contributes to the onset or progression of this common late life dementia. To address this question, we studied neuropathological and behavioral consequences of single versus repetitive mild TBI (mTBI) in transgenic (Tg) mice (Tg2576) that express mutant human Aβ precursor protein, and we demonstrate elevated brain Aβ levels and increased Aβ deposition. Nine-month-old Tg2576 and wild-type mice were subjected to single (n = 15) or repetitive (n = 39) mTBI or sham treatment (n = 37). At 2 d and 9 and 16 weeks after treatment, we assessed brain Aβ deposits and levels in addition to brain and urine isoprostanes generated by lipid peroxidation in these mice. A subset of mice also was studied behaviorally at 16 weeks after injury. Repetitive but not single mTBI increased Aβ deposition as well as levels of Aβ and isoprostanes only in Tg mice, and repetitive mTBI alone induced cognitive impairments but no motor deficits in these mice. This is the first experimental evidence linking TBI to mechanisms of AD by showing that repetitive TBI accelerates brain Aβ accumulation and oxidative stress, which we suggest could work synergistically to promote the onset or drive the progression of AD. Additional insights into the role of TBI in mechanisms of AD pathobiology could lead to strategies for reducing the risk of AD associated with previous episodes of brain trauma and for preventing progressive brain amyloidosis in AD patients. |
| Databáze: | OpenAIRE |
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