α-Tocopherol Protects Against Oxidative Stress in the Fragile X Knockout Mouse: an Experimental Therapeutic Approach for the Fmr1 Deficiency
| Autor: | Fernando Rodríguez de Fonseca, Ignacio del Arco-Herrera, Yanina Romero-Zerbo, Lourdes Sanchez, Yolanda de Diego-Otero, Rajaa El Bekay, Juan Decara |
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| Rok vydání: | 2008 |
| Předmět: |
Male
rac1 GTP-Binding Protein Aging medicine.medical_specialty Protein Kinase C-alpha Free Radicals alpha-Tocopherol In Vitro Techniques Biology medicine.disease_cause Protein oxidation Antioxidants Pathogenesis Fragile X Mental Retardation Protein Mice Internal medicine Conditioning Psychological medicine Animals Mice Knockout Pharmacology Behavior Animal Dose-Response Relationship Drug Macroorchidism Neuropeptides Fear medicine.disease FMR1 Acetylcysteine rac GTP-Binding Proteins Enzyme Activation Rac GTP-Binding Proteins Fragile X syndrome Oxidative Stress Psychiatry and Mental health Phenotype Endocrinology Fragile X Syndrome Knockout mouse Exploratory Behavior Stress Psychological Oxidative stress |
| Zdroj: | Neuropsychopharmacology. 34:1011-1026 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/npp.2008.152 |
| Popis: | Fragile X syndrome is the most common genetic cause of mental disability. The mechanisms underlying the pathogenesis remain unclear and specific treatments are still under development. Previous studies have proposed an abnormal hypothalamic-pituitary-adrenal axis and high cortisol levels are demonstrated in the fragile X patients. Additionally, we have previously described that NADPH-oxidase activation leads to oxidative stress in the brain, representing a pathological mechanism in the fragile X mouse model. Fmr1-knockout mice develop an altered free radical production, abnormal glutathione homeostasis, high lipid and protein oxidation, accompanied by stress-dependent behavioral abnormalities and pathological changes in the first months of postnatal life. Chronic pharmacological treatment with alpha-tocopherol reversed pathophysiological hallmarks including free radical overproduction, oxidative stress, Rac1 and alpha-PKC activation, macroorchidism, and also behavior and learning deficits. The restoration of the oxidative status in the fragile X mouse emerges as a new and promising approach for further therapeutic research in fragile X syndrome. |
| Databáze: | OpenAIRE |
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