Study of the crosstalk between microglia and oligodendrocyte-related cells in central nervous system myelination through interactomics

• Autores: Jennifer Vanessa Enrich Bengoa
• Directores de la Tesis: Irene Roman Degano (dir. tes.), Alejandro Perálvarez Marín (codir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2022
• Idioma: inglés
• Tribunal Calificador de la Tesis: Raúl Estevez Povedano (presid.), Enrique Querol Murillo (secret.), Merce Izquierdo Serra (voc.)
• Programa de doctorado: Programa de Doctorado en Bioquímica, Biología Molecular y Biomedicina por la Universidad Autónoma de Barcelona
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Demyelinating disorders such as multiple sclerosis (MS) are characterized by myelin destruction and impaired remyelination due to a failure in oligodendrocyte progenitor cells (OPCs) differentiation to mature oligodendrocytes. This thesis aims to expand the knowledge about the microglia-OPCs crosstalk in (re)myelination and demyelination. Several studies support that microglia is necessary for OPCs differentiation, besides, previous interactomic studies from our lab studies found that Transient Receptor Potential Vanilloid 2 (TRPV2), which is expressed in the central nervous system (CNS), OPCs and glial cells, interact with key myelin proteins, suggesting a possible function of TRPV2 in myelination.

    First, in a single-protein-focused study, we have compiled information about TRPV2 trafficking to the membrane as a tool to understand the function and regulation of the channel towards the plasma membrane, followed by the validation of TRPV2 interaction with the important key myelin proteins. Then, we analyzed the effect on TRPV2 expression of pro- and anti-inflammatory environments, but also in experimental mice models such as jimpy mutant mice, cuprizone, experimental autoimmune encephalomyelitis (EAE), and in human MS samples. These results observed that TRPV2 expression is altered in these animal models and MS human samples, and also that trafficking and subsequent activation is found in microglia and OPCs in pro-inflammatory environments.

    Second, we performed a transcriptomic data analysis of microarray studies performed in cuprizone-treated mice to infer the ligand-receptor and the ligand-target pairs regarding microglia-OPCs crosstalk. This last part of the work led us to the discovery of new microglia/OPCs biomarkers with relevant in the pathophysiology of de-/re-myelination, also providing an omics tool which could be used to analyze the cross-talk of any pair of cell types with transcriptomic data available.