Loss of Specific microRNA Seen to Lessen Disease Severity and Myelin Loss in MS Mouse Model

Jose Marques Lopes, PhD avatar

by Jose Marques Lopes, PhD |

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Removing a specific microRNA molecule — miR-150 – eased disease severity, inflammation, and loss of myelin in a mouse model of multiple sclerosis (MS), researchers report.

Their study, “Silencing miR-150 Ameliorates Experimental Autoimmune Encephalomyelitis,” was published in the journal Frontiers in Neuroscience.

Micro RNAs (miRNAs) are tiny RNA molecules that regulate gene expression (or activity), and are involved in various biological functions, including the immune response.

One miRNA with a role in immune function is miR-150. This RNA is produced in immature B- and T-cells, as well as those of the immune system, and also works to regulate their development. Genetic deletion of this miRNA is known to boost T-cell-dependent antibody responses in mice.

Despite considerable data on this molecule, its role in MS is still unknown. Scientists believe that MS is initially mediated by T-cells attacking myelin — the protective layer of nerve fibers — followed by amplified immune response and neurodegeneration. However, immune B-cells are also key players in MS progression through their release of inflammatory molecules known as cytokines, and of autoantibodies (antibodies that attack the body’s own tissues).

Current evidence indicates that miR-150 levels differ in MS patients. To better assess this molecule’s role in MS, a research team at China’s Central South University used a MS mouse model called experimental autoimmune encephalomyelitis (EAE) model with a genetic deletion of miR-150.

They found disease severity was lower in EAE mice without miR-150 compared to EAE mice with this molecule, measured through daily evaluation of clinical scores of neurological symptoms in these animals.

EAE mice without miR-150 also had lesser evidence of inflammatory cells in the spinal cord 25 days after EAE induction, and of myelin loss (demyelination). Likewise, and again in comparison to diseased mice with miR-150, they had higher levels of a protein called MBP, a major component of myelin.

“These results suggest that deletion of miR-150 reduces myelin pathology,” the researchers wrote.

They also found that deleting miR-150 eased the activation of microglia and astrocytes in the spinal cord — two cell types implicated in MS. While microglia are the primary immune cells of the central nervous system, astrocytes have various functions, including the formation of the blood-brain barrier and response to injury.

Mice lacking this microRNA also were found to have lower levels of T-cell subtypes CD3+, CD4+, and CD8+, and of CD19+ B-cells in the spleen – where miR-150 is highly produced – than EAE mice with miR-150. Studies report that MS patients have higher levels of these immune cells than healthy controls.

MiR-150 deletion also reduced mRNA levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in both spleen and spinal cord.

“miR-150 deletion reduces EAE disease severity and this may be due to inhibition of immune response, cytokine release and attenuate CNS [central nervous system] inflammation and demyelinated lesions,” the scientists wrote.

Future studies need to explore how this deletion inhibits disease progression, and whether it may be a viable approach for treating MS, the researchers noted.

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