Neurokemiska förändringar vid Parkinsons sjukdom och L-Dopa inducerade dyskinesier studerade med avbildande masspektrometri

Tidsperiod: 2019-01-01 till 2022-12-31

Projektledare: Per Andrén

Medarbetare: Per Svenningsson, Luke Odell

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 3 270 000 SEK

Mass spectrometry imaging (MSI) is an in vitro imaging technology for visualizing and quantifying the distributions of multimodal chemical species within tissue samples. The speed, sensitivity, and molecular specificity of MSI enable simultaneous imaging of hundreds to thousands of molecules (in each pixel) in tissue sections at near-cellular spatial resolutions. The present project is utilizing MSI to study neurochemical changes in Parkinson’s disease (PD). In the early stages of PD, drug treatment is highly effective, but with disease progression motor complications become increasingly evident. At least half of all patients treated with L-Dopa (the dopamine replacing therapy) develop L-Dopa-induced dyskinesia (LID). No treatment exists yet for the management of LID. There is therefore a great need to define the molecular changes associated with patients that develop LID and, likewise, to discover the molecular mechanisms in those not developing LID. For the first time, novel MSI methodology is being developed to image and quantitate complete neurotransmitter systems directly in brain tissue sections. We have access to a comprehensive and truly unique biobank of primate brain tissue consisting of seven different experimental groups (n=6) including LID, as well as rodent neurotoxic and genetic PD/LID models. In summary, our novel MSI approach on neurotransmitter function involved in PD and LID may generate new targets for developing new drugs.