Spinal cord injuries (SCI) are a major public health issue. In fact, about 2,5 millions of people in the world are affected by SCI. The functional consequences of SCI as well as their psychological impact are often dramatic, no current therapy is efficient at repairing the lesioned spinal tissue or reverse loss of motor function. Following SCI, the spinal microenvironnement is compromised and pathological events such as glutamate excitotoxicity and oxidative stress contribute to the loss of neuronal cells and subsequent loss of function. This Master' s thesis is focused on the expression and localization of a potential therapeutic target, the antiporter cystine/glutamate, namely the système Xe-, implicated daily in the protection against oxidative stress and extracellular glutamate release. Initially, we have generated a rat model for cervical SCI. Then, we have studied the relative genic expression profile of the xCT subunit conferring its specificity to the système Xe- at distinct timings post trauma. lts cellular distribution has been studied in uninjured and injured spinal cords. At last, we have investigated a regulation pathway of Scl7 al 1 gene transcription coding for the système Xe- which is the transcription factor Nrf2. Moreover, confronted to specificity issues concerning the anti-xCT antibodies, we have conducted a study in order to verify their specificity to xCT protein. First, the rat experimental model of cervical SCI has been validated through functional and morphological analysis. Then, we have demonstrated an increased relative expression of xCT mRNA as early as 4 days post SCI and up to 6 weeks after SCI. Immunochemistry has indicated that neurons and glial cells seem to express xCT protein and its expression seems to be increased following SCI. In addition, we have demonstrated an increased relative mRNA expression of Nrf2 as early as 4 days post contusion but also 6 weeks later. Finally, the study of 4 different anti-xCT antibodies has not allowed confirming their specificity. That is why the results generated on this work are the basis of deeper study on xCT protein and must be confirmed once the antibodies specificity has been validated.
| la date de réponse | 12 janv. 2017 |
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| langue originale | Anglais |
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| L'institution diplômante | |
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| Superviseur | Charles Nicaise (Promoteur) |
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Study of xCT expression and localization in the healthy and injured rat spinal cord
Janssen, P. (Auteur). 12 janv. 2017
Student thesis: Master types › Master en biochimie et biologie moléculaire et cellulaire