A Potential Protective Role of Nurr1 in Multiple Sclerosis Motor Cortex
Jonathan Pansieri1, Marco Pisa3, Richard Yates4, Sydney Yee5, Margaret Esiri5, Gabriele De Luca2
1Nuffield department of Clinical Neurosciences, University of Oxford, 2University of Oxford, 3Nuffield Department of Clinical Neurosciences, University of Oxford, 4Green-Templeton College, 5Nuffield Department of Clinical Neurosciences
Objective:

We investigated Nurr1 expression in progressive MS motor cortex and evaluated its relationship with motor cortical pathology. 

 

Background:

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. 

 

Design/Methods:

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.

Results:
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.
Conclusions:

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.

10.1212/WNL.0000000000202921