Gene expression analysis of normal appearing brain tissue in an animal model for multiple sclerosis revealed grey matter alterations, but only minor white matter changes

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Recent studies suggest that, beside focal lesions, diffuse inflammatory and degenerative processes take place throughout the MS brain. Especially, molecular alterations in the so-called normal appearing white matter suggest the induction of neuroprotective mechanisms against oxidative stress preserving cellular homeostasis and function. In this study we investigated whether in an animal model for MS, namely in experimental autoimmune encephalomyelitis (EAE), similar changes occur. We isolated normal appearing white and grey matter from the corpus callosum and the above lying cerebral cortex from DA rats with rMOG-induced EAE and carried out a gene expression analysis. Examination of corpus callosum revealed only minor changes in EAE rats. In contrast, we identified a number of gene expression alterations in the cerebral cortex even though morphological and cellular alterations were not evident. One of the most striking observations was the downregulation of genes involved in mitochondrial function as well as a whole set of genes coding for different glutamate receptors. Our data imply that molecular alterations are present in neurons far distant to inflammatory demyelinating lesions. These alterations might reflect degenerative processes induced by lesion-mediated axonal injury in the spinal cord. Our results indicate that the MOG-induced EAE in DA rats is a valuable model to analyze neuronal alterations due to axonal impairment in an acute phase of a MS-like disease, and could be used for development of neuroprotective strategies.