INVESTIGADORES
SETTON Clara Patricia
congresos y reuniones científicas
Título:
Indomethacin effect on BMMC migration: Prostaglandin synthesis inhibition or PPARɣ activation?
Autor/es:
USACH VANINA; CASALI CI; GONZALO PIÑERO; PARRA LEANDRO; WEBER K; PAULA A, SOTO; FERNÁNDEZ TOMÉ MC; SETTON, CLARA P
Lugar:
Chicago
Reunión:
Congreso; 45th Annual Meeting of the Society for Neuroscience; 2015
Institución organizadora:
Society for Neuroscience
Resumen:
Demyelination is one of the hallmarks of the Wallerian degeneration (WD) process and cell therapy is among the strategies under study to induce remyelination. Results from our group obtained in a reversible model of WD induced by the crush of the rat sciatic nerve demonstrated the spontaneous migration of endogenous or transplanted bone marrow mononuclear cells (BMMC) exclusively to the injured nerve. Once in the ipsilateral nerve, some BMMC colocalized with Schwann cell markers and nerve fiber markers, which accelerated the regeneration process. On the basis of these results, the aim of the present work was to evaluate whether prostaglandins (PGs), one of the molecules generated during the inflammatory process associated with injury, is one of the signals involved in the migration and recruitment of BMMC to the demyelinated nerve. To this end, adult Wistar rats were submitted to sciatic nerve crush and one group of animals was immediately transplanted BMMC through the sacra artery. The presence of BMMC in the injured nerve was evaluated through confocal microscopy 24 h, 3 and 5 days post injury; the expression of ciclooxygenase 2 (Cox-2) was evaluated at 24 and 72 h and the synthesis of PGs was evaluated between 0 and 24 h post crush, through Western blot and PG radioconversion, respectively. Besides, the effect of a non-steroidal anti-inflammatory drug as indomethacin on the migration of BMMC and PG biosynthesis was analyzed by treating animals with a subcutaneous injection of indomethacin 50 mg/kg/day the day of the lesion and the previous day, and 5 mg/kg/day the subsequent days. The results obtained show that, as soon as 24 h post injury, BMMC arrived at the edges of the ipsilateral nerve, and after 3 days they became part of it. Our results demonstrate the biosynthesis of PGE2, PGD2 and PGJ2 in sciatic nerve homogenates, and that their levels did not change significantly as a consequence of the lesion. Although indomethacin inhibited the migration of transplanted BMMC to the injured sciatic nerve, the biosynthesis of PGE2 and PGD2 was not affected. Surprisingly, indomethacin promoted a significant increase in PGJ2 both in the contralateral and the ipsilateral nerves as well as in the control nerve. This increase was dose-dependent, as rats treated with 12.5 or 25 mg/kg showed a smaller increase in PGJ2 synthesis.In the light of these results, indomethacin action on BMMC migration may be thought to occur through an independent PG-mediated mechanism such as the PPARɣ pathway. Further experiments are necessary to elucidate indomethacin effect on BMMC migration and on the degeneration-regeneration process.