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

• Published in: Nature nanotechnology Vol. 12; no. 4; pp. 322 - 328
• Main Authors: Haziza, Simon, Mohan, Nitin, Loe-Mie, Yann, Lepagnol-Bestel, Aude-Marie, Massou, Sophie, Adam, Marie-Pierre, Le, Xuan Loc, Viard, Julia, Plancon, Christine, Daudin, Rachel, Koebel, Pascale, Dorard, Emilie, Rose, Christiane, Hsieh, Feng-Jen, Wu, Chih-Che, Potier, Brigitte, Herault, Yann, Sala, Carlo, Corvin, Aiden, Allinquant, Bernadette, Chang, Huan-Cheng, Treussart, François, Simonneau, Michel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-04-2017; Nature Publishing Group
• Subjects: 631/61/350/354; 639/925/352/1060; 639/925/352/2734; Abnormalities; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Autism; Autistic Disorder - genetics; Autistic Disorder - metabolism; Autistic Disorder - pathology; Bioinformatics; Biological Transport, Active - genetics; Brain diseases; Cell Tracking - methods; Cells, Cultured; Computer Science; Cytotoxicity; Fluorescence; Genetics; Glass substrates; Health risk assessment; Hippocampus - metabolism; Hippocampus - pathology; letter; Localization; Materials Science; Mice; Mice, Transgenic; Microscopy; Microscopy, Fluorescence - methods; Microscopy, Video - methods; Nanocrystals; Nanodiamonds - chemistry; Nanostructure; Nanotechnology; Nanotechnology and Microengineering; Neurons; Neurons - metabolism; Neurons - pathology; Neurosciences; Patients; Quantum dots; Risk analysis; Risk factors; Tracking; Transport; World population; France; Italy; Taiwan
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/nnano.2016.260

Tracking fluorescent nanodiamond inside branches of neurons is a sensitive method to measure the changes in intraneuronal transport due to genetic risk factors associated with brain diseases.
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
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. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients
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,
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, 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
4
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.