Aberrant mitochondrial bioenergetics in the cerebral cortex of the Fmr1 knockout mouse model of fragile X syndrome
Aberrant mitochondrial bioenergetics in the cerebral cortex of the Fmr1 knockout mouse model of fragile X syndrome
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DOI：
10.1515/hsz-2019-0221
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发表时间：
2020-04-01
影响因子：
3.7
通讯作者：
Catania, Maria Vincenza
中科院分区：
文献类型：
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作者：
D'Antoni, Simona;de Bari, Lidia;Catania, Maria Vincenza
能量代谢受损可能在包括脆性X综合征(FXS)在内的神经发育障碍的发病机制中发挥作用。我们检测了Fmr1基因敲除(KO)FXS小鼠模型大脑皮层的能量状态和细胞生物能量学的某些方面，即关键的糖酵解酶、甘油-3-磷酸穿梭和线粒体呼吸链(MRC)复合体的活性。我们发现，尽管MRC复合体高度激活，但通过线粒体氧化磷酸化(OXPHOS)产生的三磷酸腺苷(ATP)受到影响，导致幼年和成年Fmr1KO小鼠的脑能量受损。因此，线粒体能量代谢的改变可能与FXS的神经损害有关。
Impaired energy metabolism may play a role in the pathogenesis of neurodevelopmental disorders including fragile X syndrome (FXS). We checked brain energy status and some aspects of cell bioenergetics, namely the activity of key glycolytic enzymes, glycerol-3-phosphate shuttle and mitochondrial respiratory chain (MRC) complexes, in the cerebral cortex of the Fmr1 knockout (KO) mouse model of FXS. We found that, despite a hyperactivation of MRC complexes, adenosine triphosphate (ATP) production via mitochondrial oxidative phosphorylation (OXPHOS) is compromised, resulting in brain energy impairment in juvenile and late-adult Fmr1 KO mice. Thus, an altered mitochondrial energy metabolism may contribute to neurological impairment in FXS.