Project

Discipline

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

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

Active participation

Title	Year

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.