Brain Neuronal Differentiation Research Articles

GDF11 protein as a geroprotector

GDF11 protein, the growth differentiation factor 11, which belongs to the TGF-β superfamily (transforming growth factor β), shows marked geroprotective effects on the cardiovascular and nervous systems. The cardioprotective and myoprotective effects of the GDF11 protein are associated with its regulation of several signaling molecules, including the MAPK–p38–mioglianin pathway. GDF11 neuroprotective action is associated with the regulation of proliferation and differentiation of brain neurons by means of changing the activity of the p57 (Kip2) and p27 (Kip1) transcription factors. GDF11 may be considered a potential target for geroprotector drugs, as was demonstrated in the case of the Glu-Asp-Arg peptide possessing similar neuroprotective and myoprotective properties as GDF11. For the Glu-Asp-Arg, Ala-Glu-AspGly, and Lys-Glu peptides, binding sites were found in the promoter region of GDF11: the CCTGC, ATTTC, and GCAG motifs, respectively.

Basic fibroblast growth factor dilates rat pial arterioles.

Basic fibroblast growth factor (bFGF) is a polypeptide that promotes the survival and differentiation of brain neurons, glia, and endothelial cells. It has been shown recently that intravenously administered bFGF lowers blood pressure by systemic vasodilation; this effect is mediated, in part, by nitric oxide (NO)-dependent mechanisms. In the current study, we directly evaluated the effect of bFGF on pial arterioles of pentobarbital-anesthetized Sprague-Dawley rats (n = 18) using the closed cranial window technique. Basic FGF (5-200 ng/ml) produced dose-dependent vasodilation; maximal vessel diameter (approximately 120% of control) was reached at 100 ng/ml. No vasodilation was found when bFGF was heat inactivated, or preincubated with blocking antibody. Moreover, bFGF-induced vasodilation was attenuated by coadministration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), consistent with an NO-dependent mechanism. These results suggest that bFGF may play an important role in the regulation of cerebrovascular tone and cerebral blood flow.