| First Author | Kosaraju J | Year | 2020 |
| Journal | Exp Neurol | Volume | 334 |
| Pages | 113454 | PubMed ID | 32877653 |
| Mgi Jnum | J:301253 | Mgi Id | MGI:6503382 |
| Doi | 10.1016/j.expneurol.2020.113454 | Citation | Kosaraju J, et al. (2020) Metformin promotes CNS remyelination and improves social interaction following focal demyelination through CBP Ser436 phosphorylation. Exp Neurol 334:113454 |
| abstractText | Individuals with demyelinating diseases often experience difficulties during social interactions that are not well studied in preclinical models. Here, we describe a novel juvenile focal corpus callosum demyelination murine model exhibiting a social interaction deficit. Using this preclinical murine demyelination model, we discover that application of metformin, an FDA-approved drug, in this model promotes oligodendrocyte regeneration and remyelination and improves the social interaction. This beneficial effect of metformin acts through stimulating Ser436 phosphorylation in CBP, a histone acetyltransferase. In addition, we found that metformin acts through two distinct molecular pathways to enhance oligodendrocyte precursor (OPC) proliferation and differentiation, respectively. Metformin enhances OPC proliferation through early-stage autophagy inhibition, while metformin promotes OPC differentiation into mature oligodendrocytes through activating CBP Ser436 phosphorylation. In summary, we identify that metformin is a promising remyelinating agent to improve juvenile demyelination-associated social interaction deficits by promoting oligodendrocyte regeneration and remyelination. |
