Investigation of the Subcellular Neurotoxicity of Amyloid-beta Using a Device Integrating Microfluidic Perfusion and Chemotactic Guidance
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AbstractAlzheimer's disease (AD) is a neurodegenerative disorder with the histopathological hallmark of extracellular accumulation of amyloid-beta (A beta) peptide in brain senile plaques. Though many studies have shown the neural toxicity from various forms of A beta peptides, the subcellular mechanisms of A beta peptide are still not well understood, partially due to the technical challenges of isolating axons or dendrites from the cell body for localized investigation. In this study, the subcellular toxicity and localization of A beta peptides are investigated by utilizing a microfluidic compartmentalized device, which combines physical restriction and chemotactic guidance to enable the isolation of axons and dendrites for localized pharmacological studies. It is found that A beta peptides induced neuronal death is mostly resulted from A beta treatment at cell body or axonal processes, but not at dendritic neurites. Simply applying A beta to axons alone induces significant hyperactive spiking activity. Dynamic transport of A beta aggregates is only observed between axon terminal and cell body. In addition to differential cellular uptake, more A beta-peptide secretion is detected significantly from axons than from dendritic side. These results clearly demonstrate the existence of a localized mechanism in A beta-induced neurotoxicity, and can potentially benefit the development of new therapeutic strategies for AD.
All Author(s) ListLi W, Xu Z, Xu BZ, Chan CY, Lin XD, Wang Y, Chen GC, Wang ZG, Yuan QJ, Zhu GY, Sun HY, Wu WT, Shi P
Journal nameAdvanced Healthcare Materials
Volume Number6
Issue Number7
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesEngineering, Biomedical;Nanoscience & Nanotechnology;Materials Science, Biomaterials;Engineering;Science & Technology - Other Topics;Materials Science

Last updated on 2021-22-09 at 01:12