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A novel microfluidic cell co-culture platform for the study of the molecular mechanisms of Parkinson's Disease and other synucleinopathies

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dc.contributor.authorFernandes, João T. S.
dc.contributor.authorChutna, Oldriska
dc.contributor.authorChu, Virginia
dc.contributor.authorConde, João P.
dc.contributor.authorOuteiro, Tiago
dc.date.accessioned2022-01-18T14:59:39Z
dc.date.available2022-01-18T14:59:39Z
dc.date.issued2016
dc.descriptionCopyright © 2016 Fernandes, Chutna, Chu, Conde and Outeiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.pt_PT
dc.description.abstractAlthough, the precise molecular mechanisms underlying Parkinson's disease (PD) are still elusive, it is now known that spreading of alpha-synuclein (aSyn) pathology and neuroinflammation are important players in disease progression. Here, we developed a novel microfluidic cell-culture platform for studying the communication between two different cell populations, a process of critical importance not only in PD but also in many biological processes. The integration of micro-valves in the device enabled us to control fluid routing, cellular microenvironments, and to simulate paracrine signaling. As proof of concept, two sets of experiments were designed to show how this platform can be used to investigate specific molecular mechanisms associated with PD. In one experiment, naïve H4 neuroglioma cells were co-cultured with cells expressing aSyn tagged with GFP (aSyn-GFP), to study the release and spreading of the protein. In our experimental set up, we induced the release of the contents of aSyn-GFP producing cells to the medium and monitored the protein's diffusion. In another experiment, H4 cells were co-cultured with N9 microglial cells to assess the interplay between two cell lines in response to environmental stimuli. Here, we observed an increase in the levels of reactive oxygen species in H4 cells cultured in the presence of activated N9 cells, confirming the cross talk between different cell populations. In summary, the platform developed in this study affords novel opportunities for the study of the molecular mechanisms involved in PD and other neurodegenerative diseases.pt_PT
dc.description.sponsorshipJF was supported by FCT (SFRH/BD/73908/2010). TO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB). The work was also supported by FCT through the Associated Laboratory IN—Institute of Nanoscience and Nanotechnology and the research project EXCL/CTM-NAN/0441/2012.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Neurosci. 2016 Nov 15;10:511pt_PT
dc.identifier.doi10.3389/fnins.2016.00511pt_PT
dc.identifier.eissn1662-453X
dc.identifier.issn1662-4548
dc.identifier.urihttp://hdl.handle.net/10451/50875
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationMICROFLUIDIC CULTURE PLATFORMS FOR NEUROSCIENCE RESEARCH
dc.relationIntegrated Nanosystems for High Frequency and Neuroscience Applications
dc.relation.publisherversionhttps://www.frontiersin.org/journals/neuroscience#pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectParkinson's diseasept_PT
dc.subjectAlpha-synucleinpt_PT
dc.subjectCell culturept_PT
dc.subjectCo-culturept_PT
dc.subjectInflammationpt_PT
dc.subjectMicrofluidicspt_PT
dc.subjectMicrogliapt_PT
dc.titleA novel microfluidic cell co-culture platform for the study of the molecular mechanisms of Parkinson's Disease and other synucleinopathiespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMICROFLUIDIC CULTURE PLATFORMS FOR NEUROSCIENCE RESEARCH
oaire.awardTitleIntegrated Nanosystems for High Frequency and Neuroscience Applications
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F73908%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXCL%2FCTM-NAN%2F0441%2F2012/PT
oaire.citation.titleFrontiers in Neurosciencept_PT
oaire.citation.volume10pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameOuteiro
person.givenNameTiago
person.identifier.ciencia-idBC14-20AB-8D68
person.identifier.orcid0000-0003-1679-1727
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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