Vis enkel innførsel

dc.contributor.authorValderhaug, Vibeke Devold
dc.contributor.authorHuse Ramstad, Ola
dc.contributor.authorvan de Wijdeven, Rosanne Francisca
dc.contributor.authorHeiney, Kristine
dc.contributor.authorNichele, Stefano
dc.contributor.authorSandvig, Axel
dc.contributor.authorSandvig, Ioanna
dc.identifier.citationBioRxiv. 2020, .en_US
dc.description.abstractMutations in the LRRK2 gene have been widely linked to Parkinson’s disease. The G2019S variant has been shown to contribute uniquely to both familial and sporadic forms of the disease. LRRK2-related mutations have been extensively studied, yet the wide variety of cellular and network events directly or indirectly related to these mutations remain poorly understood. In this study, we structured multi-nodal human neural networks carrying the G2019S mutation using custom-designed microfluidic chips coupled to microelectrode-arrays. By applying live imaging approaches, immunocytochemistry and computational modelling, we have revealed alterations in both the structure and function of the resulting neural networks when compared to controls. We provide first evidence of increased neuritic density associated with the G2019S LRRK2 mutation, while previous studies have found either a strong decrease, or no change, compared to controls. Additionally, we corroborate previous findings regarding increased baseline network activity compared to control neural networks. Furthermore, we can reveal additional network alterations attributable to the specific mutation by selectively inducing transient overexcitation to confined parts of the structured multi-nodal networks. These alterations, which we were able to capture both at the micro- and mesoscale manifested as differences in relative network activity and correlation, as well as in mitochondria activation, neuritic remodelling, and synaptic alterations. Our study thus provides important new insights into early signs of neural network pathology significantly expanding upon the current knowledge relating to the G2019S Parkinson’s disease mutation.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleStructural and functional alterations associated with the LRRK2 G2019S mutation revealed in structured human neural networksen_US
dc.typeJournal articleen_US
dc.relation.projectSamarbeidsorganet mellom Helse Midt-Norge og NTNU: xen_US
dc.relation.projectNorges forskningsråd: 270961en_US
dc.relation.projectRegionale forskningsfond Midt-Norge: xen_US

Tilhørende fil(er)


Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel

Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal