Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery

https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...

Demyelinating injuries in the central nervous system trigger a regenerative process that relies on coordinated responses from multiple cell types, including the innate immune system. Here, we propose that a maladaptive chronic immune response may be initiated when microglia’s capacity to clear myelin debris is overwhelmed, leading to a self-propagating immune response that impairs remyelination and causes further tissue damage. We aim to identify the molecular checkpoints in microglia/macrophages ...

Corpus callosum dissections were lysed in 300 µL STET lysis buffer (1% (v/v) Triton X-100, 150 mM NaCl, 2 mM EDTA, 50 mM TrisHCl pH 7.5) with a Precellys Evolution homogenizer (Bertin, Germany) using 0.5 mL soft tissue homogenization kit CK14 applying two cycles of 30 s with a speed of 6500rpm. After 15 min incubation on ice, samples were centrifuged at 16,000×g for 15 min to remove undissolved material and cell debris. The supernatant was transferred to a fresh protein lobind tube (Eppendorf, ...

After demyelinating injury of the central nervous system, resolution of the mounting acute innate inflammation is crucial for the initiation of a regenerative response. To identify factors in lesion recovery after demyelination injury, we used a toxin-induced model, in which a single dose of lysolecithin is injected into the corpus callosum to induce a focal demyelinating lesion. Afterwards, we investigated the proteome of demyelinating lesions at different time points post injection (dpi) in a ...