Significance Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system (CNS), leading to irreversible deficits in young adults. Its pathophysiology is believed to be influenced by environmental determinants. As far back as the 1990s, it had been suggested that there is a correlation between the consumption of cow’s milk and the prevalence of MS. Here, we not only demonstrate that a high percentage of MS patients harbor antibodies to bovine casein but also that antibody cross-reactivity between cow’s milk and CNS antigens can exacerbate demyelination. Our data broaden the current understanding of how diet influences the etiology of MS and set the stage for combining personalized diet plans with disease-modifying treatment strategies.

To date, it has remained unclear whether gastrointestinal symptoms, which are frequently observed in patients with multiple sclerosis (MS), are accompanied by pathology of the enteric nervous system (ENS). Here, the neurotransmitter signature of ENS neurons and morphological alterations of interstitial cells of Cajal (ICCs) were studied in patients with MS and mice with experimental autoimmune encephalomyelitis (EAE), which is an animal model of MS. Immunohistochemical analysis was performed on colonic whole mounts from mice with EAE and on paraffin-embedded sections of intestinal tissue from patients with MS. Antibodies against neurotransmitters or their enzymes (including vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT)) were used in conjunction with pan-neuronal markers. In addition, the presence of anoctamin 1 (ANO1)-expressing ICCs was studied. ENS changes were observed in the myenteric plexus, but they were absent in the submucosal plexus of both EAE mice and patients with MS. There was a significant decrease in the percentage of ChAT-positive neurons in EAE mice as opposed to a trend toward an increase in patients with MS. Moreover, while ANO1 expression was decreased in EAE mice, patients with MS displayed a significant increase. Although additional studies are necessary to accomplish an in-depth characterization of ENS alterations in MS, our results imply that such alterations exist and may reveal novel insights into the pathophysiology of MS.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-gated calcium channel antagonist, on the expression profile of myelin genes and proteins in the oligodendrocyte precursor cell (OPC) line Oli-Neu and in primary OPCs. Our data indicate that nimodipine does not have any effect on myelin-related gene and protein expression. Furthermore, nimodipine treatment did not result in any morphological changes in these cells. However, RNA sequencing and bioinformatic analyses identified potential micro (mi)RNA that could support myelination after nimodipine treatment compared to a dimethyl sulfoxide (DMSO) control. Additionally, we treated zebrafish with nimodipine and observed a significant increase in the number of mature oligodendrocytes (* p≤ 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes.