摘要
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.
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.
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
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)
