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Deciphering the role of Klf10 in the Cerebellum

journal of Biomedical Science and Engineering 2022年第5期15卷 140-156页

作者： Malek Kammoun Lydie Nadal-Desbarats Sandra Même Aude Lafoux Corinne Huchet Géraldine meyer-Dilhet julien Courchet Frédéric Montigny Frédéric Szeremeta William Même Vladimir Veksler jérôme piquereau Philippe Pouletaut Malayannan Subramaniam john r. Hawse jean-Marc Constans Sabine F. Bensamoun Biomechanics and Bioengineering CNrS UMr 7338 Sorbonne University—University of Technology of Compiègne Compiègne France iBrain CNrS UMr 1253 University of Tours Tours France Center for Molecular Biophysics CNRS UPR4301 Orléans France Therassay Platform University of Nantes Nantes France INSErM UMr1089 University of Nantes Nantes France CNrS UMr-5310 and INSErM U-1217 NeuroMyoGène Institute Villeurbanne France INSErM PST-ASB University of Tours Tours France INSErM UMr-S 1180 University of Paris-Saclay Chatenay-Malabry France Department of Biochemistry and Molecular Biology Mayo Clinic Rochester USA CHImerE EA7516 UPjV Faire Faces Institute Amiens France

recent studies have demonstrated a new role for Klf10, 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 Klf10 in the functional and structural properties of this brain region. In vivo (magnetic resonance imaging and localized spectroscopy, behavior analysis) and in vitro (histology, spectroscopy analysis, enzymatic activity) techniques were applied to comprehensively assess the cerebellum of wild type (WT) and Klf10 knockout (KO) mice. Histology analysis and assessment of locomotion revealed no significant difference in Klf10 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 (myo-inositol, lactate) within the KO cerebellum. Loss of Klf10 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 Klf10 plays an important role in energy production and mitochondrial function in the cerebellum.

关键词： Klf10 Cerebellum Mice Magnetic resonance Imaging and Spectroscopy metabolomics Mitochondria

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