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Co-culture of murine neurons using a microfluidic device for the study of Tau misfolding propagation

Co-culture of murine neurons using a microfluidic device for the study of Tau misfolding propagation
Co-culture of murine neurons using a microfluidic device for the study of Tau misfolding propagation
The deposition of misfolded, aggregated tau protein is a hallmark of several neurodegenerative diseases, collectively termed “tauopathies”. Tau pathology spreads throughout the brain along connected pathways in a prion-like manner. The process of tau pathology propagation across circuits is a focus of intense research and has been investigated in vivo in human post-mortem brain and in mouse models of the diseases, in vitro in diverse cellular systems including primary neurons, and in cell free assays using purified recombinant tau protein. Here we describe a protocol that takes advantage of a minimalistic neuronal circuit arrayed within a microfluidic device to follow the propagation of tau misfolding from a presynaptic to a postsynaptic neuron. This assay allows high-resolution imaging as well as individual manipulation of the releasing and receiving neuron, and is therefore beneficial for investigating the propagation of tau and other misfolded proteins in vitro.
Hippocampal culture, Image analysis, Imaging, Microfluidic device, Protein misfolding propagation, Tau
2331-8325
Hallinan, Grace
5549f978-4afd-4b1c-a4e1-6fe6530d3573
Lopez, Dianne
788874dc-95b4-4ddc-9a22-e21af349a693
Vargas-caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Hallinan, Grace
5549f978-4afd-4b1c-a4e1-6fe6530d3573
Lopez, Dianne
788874dc-95b4-4ddc-9a22-e21af349a693
Vargas-caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1

Hallinan, Grace, Lopez, Dianne, Vargas-caballero, Mariana, West, Jonathan and Deinhardt, Katrin (2020) Co-culture of murine neurons using a microfluidic device for the study of Tau misfolding propagation. Bio-protocol, 10 (16). (doi:10.21769/BioProtoc.3718).

Record type: Article

Abstract

The deposition of misfolded, aggregated tau protein is a hallmark of several neurodegenerative diseases, collectively termed “tauopathies”. Tau pathology spreads throughout the brain along connected pathways in a prion-like manner. The process of tau pathology propagation across circuits is a focus of intense research and has been investigated in vivo in human post-mortem brain and in mouse models of the diseases, in vitro in diverse cellular systems including primary neurons, and in cell free assays using purified recombinant tau protein. Here we describe a protocol that takes advantage of a minimalistic neuronal circuit arrayed within a microfluidic device to follow the propagation of tau misfolding from a presynaptic to a postsynaptic neuron. This assay allows high-resolution imaging as well as individual manipulation of the releasing and receiving neuron, and is therefore beneficial for investigating the propagation of tau and other misfolded proteins in vitro.

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Accepted/In Press date: 16 June 2020
Published date: 20 August 2020
Keywords: Hippocampal culture, Image analysis, Imaging, Microfluidic device, Protein misfolding propagation, Tau

Identifiers

Local EPrints ID: 445509
URI: http://eprints.soton.ac.uk/id/eprint/445509
ISSN: 2331-8325
PURE UUID: 0c01dc35-a539-4686-aa11-b0568a85e11a
ORCID for Mariana Vargas-caballero: ORCID iD orcid.org/0000-0003-2326-4001
ORCID for Jonathan West: ORCID iD orcid.org/0000-0002-5709-6790
ORCID for Katrin Deinhardt: ORCID iD orcid.org/0000-0002-6473-5298

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Date deposited: 14 Dec 2020 17:30
Last modified: 18 Feb 2021 17:20

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