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dc.contributor.authorValderhaug, Vibeke Devold
dc.contributor.authorHeiney, Kristine
dc.contributor.authorHuse Ramstad, Ola
dc.contributor.authorBråthen, Geir
dc.contributor.authorKuan, Wei-Li
dc.contributor.authorNichele, Stefano
dc.contributor.authorSandvig, Axel
dc.contributor.authorSandvig, Ioanna
dc.date.accessioned2022-02-16T14:08:13Z
dc.date.available2022-02-16T14:08:13Z
dc.date.created2021-05-13T10:55:55Z
dc.date.issued2021-06-18
dc.identifier.citationAmerican Journal of Physiology - Cell Physiology. 2021, 320 (6), 1-12.en_US
dc.identifier.issn0363-6143
dc.identifier.issn1522-1563
dc.identifier.urihttps://hdl.handle.net/11250/2979452
dc.description.abstractA patterned spread of proteinopathy represents a common characteristic of many neurodegenerative diseases. In Parkinson’s disease (PD), misfolded forms of alpha-synuclein proteins accumulate in hallmark pathological inclusions termed Lewy bodies and Lewy neurites. Such protein aggregates seem to affect selectively vulnerable neuronal populations in the substantia nigra and to propagate within interconnected neuronal networks. Research findings suggest that these proteinopathic inclusions are present at very early timepoints in disease development, even before clear behavioural symptoms of dysfunction arise. In this study we investigate the early pathophysiology developing after induced formation of such PDrelated alpha-synuclein inclusions, in a physiologically relevant in vitro setup using engineered human neural networks. We monitor the neural network activity using multielectrode arrays (MEAs) for a period of three weeks following proteinopathy induction to identify associated changes in network function, with a special emphasis on the measure of network criticality. Self-organised criticality represents the critical point between resilience against perturbation and adaptational flexibility, which appears to be a functional trait in self-organising neural networks, both in vitro and in vivo. We show that although developing pathology at early onset is not clearly manifest in standard measurements of network function, it may be discerned by investigating differences in network criticality states.en_US
dc.description.sponsorshipThis work was supported by The Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU; The Liaison Committee for Education, Research and Innovation in Central Norway (Samarbeidsorganet HMN, NTNU); and the SOCRATES project (NFR project agreement 270961). The TEM preparation was performed at the Cellular and Molecular Imaging Core Facility (CMIC, NTNU); The AFM and UV-vis spectroscopy were performed by Birgitte Hjelmeland McDonagh at the Norwegian Micro- and Nano-Fabrication Facility (NorFab), Norwegian University of Science and Technology (NTNU).en_US
dc.language.isoengen_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.ispartofseriesAmerican Journal of Physiology - Cell Physiology;
dc.subjectNeural networksen_US
dc.subjectElectrophysiologyen_US
dc.subjectPlasticityen_US
dc.subjectNeurodegenerative diseasesen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectSelf-organized criticalityen_US
dc.subjectSoCen_US
dc.titleEarly functional changes associated with alpha-synuclein proteinopathy in engineered human neural networksen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionacceptedVersionen_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doihttps://doi.org/10.1152/ajpcell.00413.2020
dc.identifier.cristin1909862
dc.source.journalAmerican Journal of Physiology - Cell Physiologyen_US
dc.source.volume320en_US
dc.source.issue6en_US
dc.source.pagenumber32en_US
dc.relation.projectSamarbeidsorganet mellom Helse Midt-Norge og NTNU: 90368100en_US
dc.relation.projectNorges forskningsråd: 270961en_US


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