TGF beta mediates the differentiation of neural precursor cells from the subventricular zone

DEBORA VANESA RODRIGUEZ; ANA ADAMO; LAURA IVONNE GOMEZ PINTO; PATRICIA MATHIEU

Oporto

Congreso; XIV European Meeting on Glial Cells in Health and Disease; 2019

Wiley Glia Journal

Neural progenitor cells (NPCs) from the subventricular zone (SVZ) are the source of new neurons, astrocytes and oligodendrocytes in the adult brain. Our previous results demonstrated the interplay between Notch andTGFβ signaling in adult SVZ neurosphere cultures. Through its receptor TβRII, TGFβ favored NPC glial cell fate decisions by inducing an increase in astrocytes expressing Jagged1. In turn, Jagged1 triggered Notch activation and induced Hes1 expression, thus promoting oligodendroglial cell fate and OPC proliferation. Once OPCs had migrated away from astrocytes expressing Jagged1, TGFβ induced TβRII-mediated OPC differentiation into mature OLs. Considering the possible participation of TGFβ in the repair mechanisms during demyelination, the aim of the present work is to study, both in vitro and in vivo, the changes induced by this cytokine on the cell populations arising from SVZ NPC, the resident OPCs and the inflammatory process. For in vitro experimentsSVZ NPCs obtained from control or demyelinated Wistar rats treated with a 7-day 0.6% cuprizone (CPZ) diet were cultured in the presence of TGFβ or its vehicle for 4 days. Immunocytochemistry showed no changes inNestin+, Nestin+/GFAP+ or GFAP+ populations in any of the experimental groups. Cultures obtained from demyelinated animals showed a higher proportion of PDGFRα+ cells than those obtained from control animals. The presence of TGFβ increased the proportion of PDGFRα+ cells in control cultures and showed a slight increase in cultures from demyelinated animals. For in vivo experiments control or 14-day-CPZ-treated rats were intraperitoneally injected TGFβ (100ng/kg) or its vehicle during 3 days before removing the toxic from the diet. Preliminary results obtained from corpus callosum and cortex immunohistochemistry analyses showed a slight increase in MAG+ cells concomitantly with a decrease in CD68+ cells in CPZ-treated animals. These results indicate that TGFβ might contribute to OPC differentiation during demyelination and reduce the inflammation associated to the demyelinating process. More experiments are needed to assess the impact of TGFβ on the whole demyelination/remyelination process.