Kammoun Malek, Nadal-Desbarats Lydie, Même Sandra, Lafoux Aude, Huchet Corinne, Meyer-Dilhet Géraldine, Courchet Julien, Montigny Frédéric, Szeremeta Frédéric, Même William, Veksler Vladimir, Piquereau Jérôme, Pouletaut Philippe, Subramaniam Malayannan, Hawse John R, Constans Jean-Marc, Bensamoun Sabine F
Biomechanics and Bioengineering CNRS UMR 7338, Sorbonne University-University of Technology of Compiègne, Compiègne, France.
iBrain CNRS UMR 1253, University of Tours, Tours, France.
J Biomed Sci Eng. 2022 May;15(5):140-156. doi: 10.4236/jbise.2022.155014. Epub 2022 May 30.
Recent studies have demonstrated a new role for , a Krüppel-like transcription factor, in skeletal muscle, specifically relating to mitochondrial function. Thus, it was of interest to analyze additional tissues that are highly reliant on optimal mitochondrial function such as the cerebellum and to decipher the role of in the functional and structural properties of this brain region. (magnetic resonance imaging and localized spectroscopy, behavior analysis) and (histology, spectroscopy analysis, enzymatic activity) techniques were applied to comprehensively assess the cerebellum of wild type (WT) and knockout (KO) mice. Histology analysis and assessment of locomotion revealed no significant difference in KO mice. Diffusion and texture results obtained using MRI revealed structural changes in KO mice characterized as defects in the organization of axons. These modifications may be explained by differences in the levels of specific metabolites (-inositol, lactate) within the KO cerebellum. Loss of expression also led to changes in mitochondrial activity as reflected by a significant increase in the activity of citrate synthase, complexes I and IV. In summary, this study has provided evidence that plays an important role in energy production and mitochondrial function in the cerebellum.
最近的研究表明,一种类Krüppel转录因子在骨骼肌中具有新的作用,特别是与线粒体功能有关。因此,分析其他高度依赖最佳线粒体功能的组织(如小脑)并解读该因子在这个脑区的功能和结构特性中的作用很有意义。应用磁共振成像和局部光谱分析、行为分析以及组织学、光谱分析、酶活性分析等技术全面评估野生型(WT)和该因子敲除(KO)小鼠的小脑。组织学分析和运动评估显示KO小鼠无显著差异。使用磁共振成像获得的扩散和纹理结果显示,KO小鼠存在结构变化,表现为轴突组织缺陷。这些改变可能由KO小脑中特定代谢物(肌醇、乳酸)水平的差异来解释。该因子表达的缺失还导致线粒体活性发生变化,这表现为柠檬酸合酶、复合体I和复合体IV的活性显著增加。总之,本研究提供了证据表明该因子在小脑的能量产生和线粒体功能中起重要作用。