COBRE: UL: STUDY THE ROLE OF LINGO01 IN VIVO SPINAL CORD REPAIR (SUB PKC)

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have changed the direction of our research project since the last report. LINGO-1, an inhibitory molecule and part of the Nogo receptor complex, is involved in CNS repair following spinal cord injury (SCI). This molecule transduces inhibitory signals intracellularly resulting in inhibition of axon growth. LINGO-1 signaling is modulated using LINGO-1 KO mice, DN LINGO-1, and LINGO-1 antibody in vivo (we demonstrated that DN LINGO-1 inhibition enhances the rate of MEP return following SCI). We hypothesize that negative regulation of LINGO-1 will enhance axon regrowth, remyelination, and functional improvement. LINGO-1 manipulation in vivo SCI may provide new strategies to treat SCI. We will study LINGO-1 expression under normal conditions and following SCI at different points in time and topographic sites. Temporal expression of LINGO-1 will be studied after contusion and demyelinating SCI (rRT-PCR 4hr, 1d, 3d. Western blot at 1d, 3d, 1wk. 3wks). This aim should provide insights into mammalian CNS LINGO-1 signal modulation after SCI. Negative regulation of LINGO-1 in experimental demyelination may increase the degree and rate of remyelination. Using a mouse spinal cord demyelination model in vivo, we will study whether axonal conduction, morphological, and behavioral tests, we asked whether LINGO-1 inhibition facilitates myelination. Does LINGO-1 mutation produces a greater number of immature oligodendrocytes and oligodendricytes precursor cells (OPC), or is myelin thickness enhanced? LINGO-1 reduces RhoA activation that prevents axon regeneration. We hypothesize that RhoA is upregulated during remyelination. We will also evaluate the effect of LINGO-1 inhibition on axon regeneration and collateral sprouting in a region remote from the SCI, specifically in the area of the central pattern generator (CPG) in the thoracolumbar area of the spinal cord.