Serine Racemase mediates subventricular zone neurogenesis via fatty acid metabolism.
Serine Racemase mediates subventricular zone neurogenesis via fatty acid metabolism.
复制标题
丝氨酸消旋酶通过脂肪酸代谢介导室下区神经发生。
DOI：
10.1016/j.stemcr.2023.05.015
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发表时间：
2023
影响因子：
5.9
通讯作者：
Snyder,SolomonH
中科院分区：
文献类型：
--
作者：
Roychaudhuri,Robin;Atashi,Hasti;Snyder,SolomonH
成人室下区（SVZ）是一个持续产生新生神经元的神经源性生态位。在这里，我们发现丝氨酸消旋酶（SR），一种催化l -丝氨酸和d -丝氨酸消旋的酶，通过控制新脂肪酸的合成影响成年SVZ的神经发生。种系和条件缺失SR（巢蛋白前体细胞）导致SVZ神经发生减少。nesting -cre+小鼠的脂肪酸合成酶及其底物丙二酰辅酶a的表达降低，而丙二酰辅酶a参与了脂肪酸的合成。全球脂质组学分析显示巢蛋白-cre+小鼠不同脂质亚类有显著变化。脂肪酸合成的减少是由磷酸乙酰辅酶a羧化酶介导的，该酶是amp激活的蛋白激酶独立的。L-丝氨酸和d -丝氨酸的补充均可挽救SVZ神经发生、增殖和丙二酰辅酶ain体外水平的缺陷。我们的研究表明，SR通过脂质代谢影响SVZ的成人神经发生。
The adult subventricular zone (SVZ) is a neurogenic niche that continuously produces newborn neurons. Here we show that serine racemase (SR), an enzyme that catalyzes the racemization of L-serine to D-serine and vice versa, affects neurogenesis in the adult SVZ by controllingde novofatty acid synthesis. Germline and conditional deletion of SR (nestin precursor cells) leads to diminished neurogenesis in the SVZ. Nestin-cre+ mice showed reduced expression of fatty acid synthase and its substrate malonyl-CoA, which are involved inde novofatty acid synthesis. Global lipidomic analyses revealed significant alterations in different lipid subclasses in nestin-cre+ mice. Decrease in fatty acid synthesis was mediated by phospho Acetyl-CoA Carboxylase that was AMP-activated protein kinase independent. Both L- and D-serine supplementation rescued defects in SVZ neurogenesis, proliferation, and levels of malonyl-CoAin vitro. Our work shows that SR affects adult neurogenesis in the SVZ via lipid metabolism.