Tauroursodeoxycholic Acid Enhances Mitochondrial Biogenesis, Neural Stem Cell Pool, and Early Neurogenesis in Adult Rats
Tauroursodeoxycholic Acid Enhances Mitochondrial Biogenesis, Neural Stem Cell Pool, and Early Neurogenesis in Adult Rats
复制标题
牛磺熊去氧胆酸增强成年大鼠的线粒体生物发生、神经干细胞库和早期神经发生
作者：
Rita Soares;Filipa F Ribeiro;S. Xapelli;Tânia Genebra;M. F. Ribeiro;A. Sebastião;C. Rodrigues;S. Solá
尽管神经发生发生在成年哺乳动物大脑的有限区域，但神经干细胞(NSCs)在衰老过程中或损伤后产生的神经元非常少。我们最近发现，内源性胆汁酸牛磺酸脱氧胆酸(TUDCA)是一种强大的线粒体凋亡抑制物，在神经退行性疾病动物模型中具有神经保护作用，它还通过改善线粒体的完整性和神经干细胞的功能来促进NSC的增殖、自我更新和神经元转化。在本研究中，我们利用出生后的大鼠神经球和暴露于胆汁酸的成年大鼠，探讨了TUDCA对神经源性壁龛、侧脑室下区(SVZ)和海马齿状回(DG)NSC命运的调节作用。TUDCA可显著诱导SVZ内NSC的增殖、自我更新和神经分化，但不影响DG来源的NSCs。更重要的是，TUDCA显著提高了SVZ来源的神经干细胞线粒体生物发生相关蛋白的表达水平和线粒体的抗氧化反应。最后，成年大鼠脑室内注射TUDCA显著促进了SVZ区神经干细胞的增殖和早期分化，证实了体外数据。总而言之，我们的结果强调了TUDCA在与SVZ小生境恶化和神经发生受损相关的神经疾病中的潜在作用。
Although neurogenesis occurs in restricted regions of the adult mammalian brain, neural stem cells (NSCs) produce very few neurons during ageing or after injury. We have recently discovered that the endogenous bile acid tauroursodeoxycholic acid (TUDCA), a strong inhibitor of mitochondrial apoptosis and a neuroprotective in animal models of neurodegenerative disorders, also enhances NSC proliferation, self-renewal, and neuronal conversion by improving mitochondrial integrity and function of NSCs. In the present study, we explore the effect of TUDCA on regulation of NSC fate in neurogenic niches, the subventricular zone (SVZ) of the lateral ventricles and the hippocampal dentate gyrus (DG), using rat postnatal neurospheres and adult rats exposed to the bile acid. TUDCA significantly induced NSC proliferation, self-renewal, and neural differentiation in the SVZ, without affecting DG-derived NSCs. More importantly, expression levels of mitochondrial biogenesis-related proteins and mitochondrial antioxidant responses were significantly increased by TUDCA in SVZ-derived NSCs. Finally, intracerebroventricular administration of TUDCA in adult rats markedly enhanced both NSC proliferation and early differentiation in SVZ regions, corroborating in vitro data. Collectively, our results highlight a potential novel role for TUDCA in neurologic disorders associated with SVZ niche deterioration and impaired neurogenesis.
影响因子：
4.6
作者：
Q. Shen;W. Zhong;Y. Jan;S. Temple
通讯作者：
Q. Shen;W. Zhong;Y. Jan;S. Temple