Cellular and Molecular Neurobiology
Author: Daniela Alejandra Rodriguez Carrascal | Email: danielarcarrascal@gmail.com
Daniela Rodriguez-Carrascal1°2°, Vanina Usach1°2°, Patricia Setton-Avruj1°2°
1° Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica. Cátedra de Química Biológica Patológica.
2° Instituto de Química y Fisicoquímica Biológicas “Dr Alejandro C. Paladini” (IQUIFIB), UBA-CONICET.
Peripheral neuropathies are a group of over 100 diseases that cause weakness, pain, and loss of sensory and motor functions, affecting quality of life. Current therapies only manage symptoms and fail to address the underlying pathology, emphasizing the need for new treatments that accelerate recovery before irreversible damage occurs. We have demonstrated that bone marrow-mononuclear cells (BMMC) have great therapeutic potential in nerve regeneration by migrating to the site of damage and reducing neuropathic pain. In this research, we evaluated the role of peroxisome proliferator-activated receptor gamma (PPARγ) in neuroinflammation, regeneration, and its involvement in the recruitment of multipotent cells and macrophages in the context of peripheral nerve injuries. In a rat Wallerian degeneration model promoted by the crush of the sciatic nerve, through epifluorescence and confocal microscopy, we demonstrated that indomethacin, an inhibitor of cyclooxygenase (COX) activity, a rate-limiting enzyme in prostaglandins (PG) biosynthesis, prevented BMMC migration to the injury site, as well as, decreases PGE2 levels and increases PGJ2 levels, a PPARγ endogenous ligand. Additionally, sciatic nerve crush promoted an increase in PPARγ levels that was not modified by a PPARγ agonist treatment. We are evaluating nanoapproaches to enhance the efficacy of cell therapies, exploring the molecular mechanisms associated with the signaling pathways of PPARγ in nerve regeneration.