Brain diseases such as autism and Alzheimer’s disease (each inflicting >1% of the world population) involves 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 changes in intraneuronal transport induced by brain disease-related genetic risk factors. It relies on the spontaneous internalization of optically active photostable nanoparticles by neurons in endosomes, and the subsequent tracking of their motion within neuronal branches through their optical labeling.
For two-dimensional primary neuron cultures, we used fluorescent nanodiamonds, which provide high brightness, photostability and absence of cytotoxicity. For thicker samples (3D-culture, brain slices…) we took advantage of nonlinear properties (second-harmonic generation) of silicon carbide nanoparticles which allows tracking at depth of ≈100 µm thanks to laser excitation in the near-infrared transparency window of tissues. This technique revealed abnormal intraneuronal transport in transgenic mouse models of brain diseases.
Simon Haziza, Michel Simonneau, and François Treussart, "Intraneuronal transport abnormalities revealed by optically active photostable nanoparticle tracking (Conference Presentation)," Proc. SPIE 10547, Advances in Photonics of Quantum Computing, Memory, and Communication XI, 1054702 (Presented at SPIE OPTO: January 29, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2297085.5751542184001.
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