title: Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors.
abstract: Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.
authors.affiliation: Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Cachan, Université Paris-Saclay, 91405 Orsay, France.|Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Haziza
authors.affiliation: Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Cachan, Université Paris-Saclay, 91405 Orsay, France.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mohan
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Loe-Mie
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Aude-Marie
authors.initials: AM
authors.lastname: Lepagnol-Bestel
authors.affiliation: Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Cachan, Université Paris-Saclay, 91405 Orsay, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Massou
authors.affiliation: Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Cachan, Université Paris-Saclay, 91405 Orsay, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Adam
authors.affiliation: Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Cachan, Université Paris-Saclay, 91405 Orsay, France.
authors.forename: Xuan Loc
authors.initials: XL
authors.lastname: Le
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Viard
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Institut de Génomique, Centre National de Génotypage, 91057 Evry, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Plancon
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Daudin
authors.affiliation: Institut de génétique et de biologie moléculaire et cellulaire, CNRS UMR 7104, INSERM U 964, Université de Strasbourg, 67400 Illkirch-Graffenstaden, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Koebel
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dorard
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Rose
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan.
authors.forename: Feng-Jen
authors.initials: FJ
authors.lastname: Hsieh
authors.affiliation: Department of Applied Chemistry, National Chi Nan University, Puli, Nantou Hsien 545, Taiwan.
authors.forename: Chih-Che
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Potier
authors.affiliation: Institut de génétique et de biologie moléculaire et cellulaire, CNRS UMR 7104, INSERM U 964, Université de Strasbourg, 67400 Illkirch-Graffenstaden, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Herault
authors.affiliation: Neuroscience Institute, CNR, 20129 Milano, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala
authors.affiliation: Department of Psychiatry, Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Allinquant
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan.
authors.forename: Huan-Cheng
authors.initials: HC
authors.lastname: Chang
authors.affiliation: Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Cachan, Université Paris-Saclay, 91405 Orsay, France.
authors.forename: François
authors.identifier: 0000-0002-1755-0688
authors.initials: F
authors.lastname: Treussart
authors.affiliation: Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Cachan, Université Paris-Saclay, 91405 Orsay, France.|Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris-Descartes, 75014 Paris, France.|Department of Biology, ENS Cachan, Université Paris-Saclay, 94235 Cachan, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Simonneau
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001693:Biological Transport, Active / Q000235:genetics; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D018715:Microscopy, Video / Q000379:methods; D058612:Nanodiamonds / Q000737:chemistry*; D009474:Neurons / Q000378:metabolism / Q000473:pathology
chemical_list: D058612:Nanodiamonds