Brain-derived neurotrophic factor (BDNF) plays important roles in brain development and neural function. Constitutive knockout of the splicing regulator RBM4 reduces BDNF expression in the developing brain and causes cerebellar hypoplasia, an autism-like feature. Here, we show that Rbm4 knockout induced intron 6 retention of Hsf1, leading to downregulation of HSF1 protein and its downstream target BDNF.
View Article and Find Full Text PDFA molecular and functional link between neurotrophin signaling and cerebellar foliation is lacking. Here we show that constitutive knockout of two homologous genes encoding the RNA binding protein RBM4 results in foliation defects at cerebellar lobules VI-VII and delayed motor learning in mice. Moreover, the features of Rbm4 double knockout (dKO), including impaired differentiation of cerebellar granule cells and dendritic arborization of Purkinje cells, are reminiscent of neurotrophin deficiency.
View Article and Find Full Text PDFAltered metabolism is a hallmark of aging. The tricarboxylic acid cycle (TCA cycle) is an essential metabolic pathway and plays an important role in lifespan regulation. Supplementation of α-ketoglutarate, a metabolite converted by () in the TCA cycle, increases lifespan in .
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