A Potential Protective Role of Nurr1 in Multiple Sclerosis Motor Cortex (P2-3.003)

Abstract

<h3>Objective:</h3> We investigated Nurr1 expression in progressive MS motor cortex and evaluated its relationship with motor cortical pathology. <h3>Background:</h3> Cerebral cortical inflammation and neurodegeneration are hallmark pathological features of multiple sclerosis (MS) that contribute to irreversible neurological disability. While the reason for nerve cell death is unknown, the pathogenic inflammatory role of glial cells and infiltrating lymphocytes is likely important contributors. In that context, The transcription factor Nurr1 counteracts inflammation in animal models of MS, and protects against neuronal loss in other neurodegenerative disorders, but its role in MS is not known. <h3>Design/Methods:</h3> An autopsy cohort of pathologically confirmed MS (n=46) and control (n=11) cases was used, where Nurr1 expression was related to neuronal, microglial, astrocytic and lymphocytic densities. Quantitative and semi-quantitative analyses were performed and related to pathological features. <h3>Results:</h3> Motor cortical Nurr1 was overexpressed in MS compared to control cases. Increased Nurr1 expression positively associated with neuronal densities, especially when expressed in neuronal nuclei, and associated with decreased CD8+ cytotoxic lymphocyte density and activated astrocytes. Interestingly, we observed differences in the impact of Nurr1 depending on its cortical layer/neuronal sub-cellular localisation in MS cortex. Additionally, we found that Nurr1 was expressed in microglia and astrocytes, but no relationship between microglia and Nurr1 was found. <h3>Conclusions:</h3> Our findings expand the current knowledge on Nurr1 in neurological diseases, and support the hypothesis that Nurr1 may play a dual protective role in MS by influencing inflammatory and neurodegenerative processes. Future studies elucidating the influence of Nurr1 on these processes in MS may cast light onto novel targets that may be modulated to alter clinical outcome. <b>Disclosure:</b> Dr. Pansieri has nothing to disclose. Dr. Pisa has nothing to disclose. Richard Yates has nothing to disclose. Sydney Yee has nothing to disclose. Margaret Esiri has nothing to disclose. Dr. De Luca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurology Academy. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. The institution of Dr. De Luca has received research support from NIHR, BRC (Oxford). The institution of Dr. De Luca has received research support from National Health and Medical Research (Australia). The institution of Dr. De Luca has received research support from UK MS Society. The institution of Dr. De Luca has received research support from Oxford-Quinnipiac Partnership. The institution of Dr. De Luca has received research support from US Department of Defense. The institution of Dr. De Luca has received research support from Wellcome ISSF (Oxford). The institution of Dr. De Luca has received research support from Bristol Myers Squibb. The institution of Dr. De Luca has received research support from University of Oxford (John Fell Fund). Dr. De Luca has a non-compensated relationship as a Editorial board member with MS Journal that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Vice-Chair of Grant Review Panel with UK MS Society that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Steering Group member with MS Academy that is relevant to AAN interests or activities.