Adrian Corbett, Ph.D. (Advisor); Christopher Wyatt, Ph.D. (Committee Member); Sherif Elbasiouny, Ph.D. (Committee Member)
Master of Science (MS)
Whereas immune modulation has proven beneficial in multiple sclerosis (MS), we hypothesized that targeting down-stream modulators of neurogenesis and subsequent remyelination may offer an additional, if not superior, point of intervention in an attempt to repair damage and recover lost function. As such, the present study assessed the effectiveness of 30-day administration of the drug combination fluoxetine (5 mg/kg), simvastatin (1 mg/kg), and ascorbic acid (50 mg/kg) (FSA) on an early marker of neurogenesis, doublecortin (DCX), and functional recovery using the Montoya Staircase following lysolecithin-induced focal demyelination of the corpus callosum in middle-aged (10-11 month) male and female rats. Lysolecithin injection resulted in a functional deficit of about 27.5% for ipsilateral function and about 30% for contralateral function. Male control animals demonstrated a full recovery of function, for both ipsilateral and contralateral measures. Consistent with this finding, male controls also had the highest average DCX density/volume, although a significant correlation between the two measures was not seen. Male FSA animals also demonstrated recovery of function; however, it was blunted relative to male controls and did not reach pre-surgery baseline levels. Likewise, DCX density/volume was lower in male FSA than male controls. Female control animals appeared to have impaired natural repair, demonstrating only limited functional recovery. After an initial larger functional deficit, female FSA animals showed functional recovery consistent with female controls for both ipsilateral and contralateral function, in neither case reaching pre-injury baseline performance. Consistent with the observed male to female functional differences, female DCX density and volume were significantly lower than in males. Taken together, these results indicate an innate difference in middle-aged male and female rat neurogenesis response to injury. The drug combination used in this study appeared to impair rather than augment recovery (both in terms of neurogenesis and function), a feature most pronounced in the male rats.
Department or Program
Department of Neuroscience, Cell Biology, and Physiology
Year Degree Awarded
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