title: Investigation of the Subcellular Neurotoxicity of Amyloid-β Using a Device Integrating Microfluidic Perfusion and Chemotactic Guidance.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder with the histopathological hallmark of extracellular accumulation of amyloid-β (Aβ) peptide in brain senile plaques. Though many studies have shown the neural toxicity from various forms of Aβ peptides, the subcellular mechanisms of Aβ 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 Aβ 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 Aβ peptides induced neuronal death is mostly resulted from Aβ treatment at cell body or axonal processes, but not at dendritic neurites. Simply applying Aβ to axons alone induces significant hyperactive spiking activity. Dynamic transport of Aβ aggregates is only observed between axon terminal and cell body. In addition to differential cellular uptake, more Aβ-peptide secretion is detected significantly from axons than from dendritic side. These results clearly demonstrate the existence of a localized mechanism in Aβ-induced neurotoxicity, and can potentially benefit the development of new therapeutic strategies for AD.
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Bingzhe
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Chung Yuen
authors.initials: CY
authors.lastname: Chan
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Ganchao
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, 999077, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, 999077, China.
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave Kowloon, Hong Kong, SAR, 999077, China.|Shenzhen Research Institute, City University of Hong Kong, Shenzhen, 518057, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology; D046210:Microfluidic Analytical Techniques; D021381:Protein Transport; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer's disease; amyloid-beta; microfluidic device; neural guidance; subcellular toxicity