Role of adenosine signaling in oligodendrocyte regeneration and remyelination

• Applicant: Dr. Wenhui Huang
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 462650276

Identifying the molecular mechanisms regulating oligodendrocyte (OL) regeneration and remyelination is key to understand neurodegenerative pathologies such as multiple sclerosis (MS). Our preliminary studies targeting functions of A1 adenosine receptors (A1ARs) lead us to hypothesize that adenosine signaling may regulate OL regeneration and remyelination. Therefore, we propose to investigate the dynamic changes of extracellular adenosine levels in the brain using a mouse model of de-/remyelination. We will utilize CD73/Nt5e-deficient and cell type-specific A1AR knockout mice to dissect the molecular and cellular steps of glial adenosine signaling in the regenerative process in vivo. High-throughput RNA sequencing, electron microscopy and the Erasmus ladder test of motor behavior will be employed to assess the impact of adenosine signaling at the molecular, cellular and systems level. Thereby, we may provide novel insights for developing therapeutic approaches of myelin repair.

• DFG Programme: Research Grants