Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

Simon Haziza (1, 2) , Nitin Mohan (1) , Yann Loe-Mie (2) , Aude-Marie Lepagnol-Bestel (2) , Sophie Massou (1) , Marie-Pierre Adam (1) , Xuan Loc Le (1) , Julia Viard (2) , Christine Plancon (3) , Rachel Daudin (2) , Pascale Koebel (4) , Emilie Dorard (2) , Christiane Rose (2) , Feng-Jen Hsieh (5) , Chih-Che Wu (6) , Brigitte Potier (2) , Yann Hérault (4) , Carlo Sala (7) , Aiden Corvin (8) , Bernadette Allinquant (2) , Huan-Cheng Chang (5) , François Treussart (1) , Michel Simonneau (1, 2)

1 LAC - Laboratoire Aimé Cotton
2 U894 / UMS 1266 - Institut de psychiatrie et neurosciences
3 IG - Institut de Génomique d'Evry
4 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
5 IAMS - Institute of Atomic and Molecular Sciences [Taipei]
6 NCNU - National Chi Nan University
7 Istituto di Neuroscienze
8 Trinity College Dublin

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.

Domains: Bioinformatics [q-bio.QM]

Simon Haziza, Nitin Mohan, Yann Loe-Mie, Aude-Marie Lepagnol-Bestel, Sophie Massou, et al.. Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors. Nature Nanotechnology, 2017, 12 (4), pp.322-328. ⟨10.1038/nnano.2016.260⟩. ⟨pasteur-02873510⟩