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Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Australian National University, Australia.
Australian National University, Australia.
South Australian Health and Medical Research Institute, Australia; Flinders University of South Australia, Australia.
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2017 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 54, no 6, 4486-4495 p.Article in journal (Refereed) Published
Abstract [en]

Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinsons disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1(-/-))] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra(-/-))] to wild-type (wt) mice at young and middle age. Their motor skills were evaluated by the open-field and rotarod tests, and quantification of their dopamine neurons and activated microglia within the substantia nigra were performed by immunohistochemistry. IL-1ra(-/-) mice showed an age-related decline in motor skills, a reduced number of dopamine neurons, and an increase in activated microglia when compared to wt or casp1(-/-) mice. Casp1(-/-) mice had similar changes in motor skills and dopamine neurons, but fewer activated microglia cells than wt mice. Our results suggest that the overactivated IL-1 pathway occurring in IL-1ra(-/-) mice in the absence of inflammatory interventions (e.g., intracerebral injections performed in animal models of PD) increased activated microglia, decreased the number of dopaminergic neurons, and reduced their motor skills. Decreased IL-1 activity in casp1(-/-) mice did not yield clear protective effects when compared with wt mice. In summary, in the absence of overt brain insults, chronic activation of the IL-1 pathway may promote pathological aspects of PD per se, but its impairment does not appear to yield advantages over wt mice.

Place, publisher, year, edition, pages
HUMANA PRESS INC , 2017. Vol. 54, no 6, 4486-4495 p.
Keyword [en]
Open-field; Rotarod; Substantia nigra; Dopaminergic neuron; Microglia
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-139522DOI: 10.1007/s12035-016-9988-xISI: 000405710900045PubMedID: 27356916OAI: oai:DiVA.org:liu-139522DiVA: diva2:1130193
Note

Funding Agencies|John Curtin School of Medical Research, The Australian National University

Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-29

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