PPARγ pathway: a potential therapeutic target for peripheral nerve injuries

CASALI, CECILIA IRENE; PARRA, LEANDRO; USACH, VANINA; PIÑERO, GONZALO; . FERNÁNDEZ TOME, MARIA DEL CARMEN; MAAG, MARÍA FERNANDA; SOTO, PAULA; SETTON-AVRUJ, PATRICIA S

Virtual

Congreso; XXXV Congreso Anual Sociedad Argentina de Neurociencias (SAN), virtual; 2020

Sociedad Argentina de Investigación en Neurociencias

Inflammation plays a key role in Wallerian degeneration (WD), as evidenced by an increase in the expression of cytokines and chemokines and arachidonic acid metabolites such as prostaglandins (PG), among others. PGJ2 is the endogenous ligand of PPARγ, a transcription factor which regulates the expression of anti-inflammatory genes. PPARγ activation is also promoted by pharmacological agonists such as rosiglitazone and indomethacin.Our group has previously shown the spontaneous migration of systemically transplanted multipotent bone marrow cells (BMMC) to the injured sciatic nerve to exert a beneficial effect on nerve regeneration through an immunomodulatory mechanism. The aim of the present work is to evaluate whether the PPARγ pathway is involved in BMMC immunomodulatory effects in a WD model promoted by 8-second crush of the sciatic nerve.An increase in PGE2 and PGJ2, as well as in Cox-1 and PPARγ levels were promoted as a consequence of injury, while indomethacin selectively blocked the increase in PGE2. Although BMMC, indomethacin and rosiglitazone promoted an increase in PPARγ and COX-1 levels in naïve nerves, a synergic effect upon that promoted by sciatic nerve crush was not observed.Our results suggest the participation of the PPARγ pathway in the immunomodulatory effect promoted by systemically transplanted BMMC and open a new field for potential therapeutic strategies after peripheral nerve injuries.