Project

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Unscrambling the Influence of Brain Structure on Alzheimer’s Disease: A High-Throughput Cell Micropatterning System

Applicant Kunze Anja
Number 140643
Funding scheme Fellowships for prospective researchers
Research institution Di Carlo Microfluidics Laboratory Department of Bioengineering UCLA
Institution of higher education Institution abroad - IACH
Main discipline Other disciplines of Engineering Sciences
Start/End 01.04.2012 - 30.09.2013
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All Disciplines (6)

Discipline
Other disciplines of Engineering Sciences
Microelectronics. Optoelectronics
Cellular Biology, Cytology
Electrical Engineering
Other disciplines of Physics
Biophysics

Keywords (15)

Microfluidics; High throughput; Primary neurons; Axon length; Alzheimer's disease; Tau hyperphosphorylation; Neurotherapeutics; Cell culture; High-throughput microfluidic; single cell analysis; neural cell culture; magnetic nanoparticles; neurodegenerative diseases; brain structure; mechanical forces

Lay Summary (English)

Lead
Lay summary
Neurodegenerative diseases e.g., Alzheimer's disease, propagate in the brain through specific patterns. The influence of the brain structure on this propagation patterns is hardly understood and will be investigated in this project using microfluidic high-throughput technology.

The highly folded structure of the cerebral cortex in human brains has a major influence on human brain function. It has been hypothesized that mechanical strain, induced through fiber connections between neurons during the development of the cerebral cortex, is the underlying driving force behind this folded landscape. The folded architecture causes coexistence of different axonal fiber lengths in the cortex. Now, many neurodegenerative diseases (ND), including Alzheimer's, show a heterogeneous propagation pattern regarding brain structure and fiber lengths. Alzheimer's disease (AD) arises in elder brains, mostly over 65. It affects in an early stage our short-term memory and attention. Then AD progresses in the brain to regions which influence our learning, language and cognition. These progression patterns are hardly understood and the brain structure might have a high impact on it.

To unscramble the relation between the cortical structure and possible disease propagation, this project proposes the development of a novel microtechnology based high-throughput cell culture platform, suitable for multivariate structural parameter analysis. This cell culture platform will combine local cell patterning methods, primary cell culture and manipulation of cell shapes using magnetic nanoparticles. Quantitative data analysis will be based on high resolution confocal microscopy and high through put screening assays.

Standard cell culture studies as well as brain slice studies currently lack simultaneous control over structural parameters such as cortical thickness, local cell density and axonal length. Therefore, microtechnology based cell culture assays that do provide control over the cell location, cell-cell interaction and local chemical gradients of nutrients and signals will represent a major achievement in understanding the propagation of neurodegenerative diseases, such as Alzheimer's. This project will include structural aspects to the context of propagating neurodegenerative diseases, which may help finding effective neuroprotective pharmaceutics against Alzheimer's disease.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Publications

Publication
Astrocyte–neuron co-culture on microchips based on the model of SOD mutation to mimic ALS
Kunze Anja, Lengacher Sylvain, Dirren Elisabeth, Aebischer Patrick, Magistretti Pierre J., Renaud Philippe (2013), Astrocyte–neuron co-culture on microchips based on the model of SOD mutation to mimic ALS, in Integrative Biology, 5(7), 964-975.
Microchip based multi parameter study of magnetic nanoparticle induced neurite outgrowth
Kunze Anja, Tseng Peter, Caputo Anna, Schweizer Felix E., Di Carlo Dino (2013), Microchip based multi parameter study of magnetic nanoparticle induced neurite outgrowth, in 14th UC Systemwide Bioengineering Symposium, San Diego.
Locally induced Alzheimer’s disease in 3D microengineered neuronal cell cultures
Kunze Anja, Renaud Philippe (2012), Locally induced Alzheimer’s disease in 3D microengineered neuronal cell cultures, in Society for Neuroscience, 2012, New Orleans, LA.
MICRO MAGNET CHIPS TO STUDY NANOPARTICLE FORCE-INDUCED NEURAL. CELL MIGRATION
Kunze Anja, Tseng Peter, Murray Coleman, Caputo Anna, Schweizer Felix E., Di Carlo Dino, MICRO MAGNET CHIPS TO STUDY NANOPARTICLE FORCE-INDUCED NEURAL. CELL MIGRATION, in 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Freiburg, Germany.

Collaboration

Group / person Country
Types of collaboration
Felix Schweizer Lab at UCLA United States of America (North America)
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
BRI Neuroscience Poster Session at UCLA Poster 04.12.2012 Los Angeles, CA, United States of America Kunze Anja;


Awards

Title Year
14th Annual UC Systemwide Bioengineering Symposium Award for excellent presentation in "Microchip Based Multi Parameter Study of Magnetic Nanoparticle Induced Neurite Outgrowth". 2013

Abstract

The highly convoluted structure of the cerebral cortex determines our proper brain function. It has been hypothesized that mechanical strain, induced through corticocortical connections during morphogenesis, is the underlying driving force behind this folded landscape. The folded architecture causes coexistence of different axonal fiber lengths in the cortex. Now, many neurodegenerative diseases (ND), including Alzheimer’s, show a heterogeneous propagation pattern regarding brain structure and fiber lengths. To unscramble the relation between cortical structure and disease propagation, we propose the development of a novel microtechnology based high-throughput cell culture platform, suitable for multivariate structural parameter analysis. Indeed, current in vivo experiments cannot provide simultaneous control over structural parameters such as cortical thickness, local cell density and axonal length. Therefore, microtechnology based cell culture assays that do provide control over the 3D pattern, cell-cell interaction and local chemical gradients of nutrients and signals will represent a major achievement in the further understanding of NDs, such as Alzheimer’s. Including structural aspects in the development of neurotherapeutics against Alzheimer’s disease may help finding neuroprotective pharmaceutics.
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