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Updated: Jul 14, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Increased catechol-O-methyltransferase activity and protein expression in OX-42-positive cells in the substantia
Teemu Helkamaa1, Ilkka Reenilä, Raimo K Tuominen
1Institute of Biomedicine, Pharmacology, University of Helsinki, Finland. teemu.helkamaa@helsinki.fi
Abstract:
Activated microglial cells are found in the substantia nigra and the striatum of Parkinson's disease patients. These cells have been shown to express catechol-O-methyltransferase activity which may increase during pathological conditions. Lipopolysaccharides are potent activators of microglial cells. After paranigral lipopolysaccharide infusion to rats we observed intense microglial activation around the lesion area followed by a delayed injury in nigrostriatal pathway in 2 weeks. Simultaneously, catechol-O-methyltransferase activity in the substantia nigra was gradually increased up to 213%. In the Western blot the amount of soluble COMT and membrane bound COMT proteins were increased by 255% and 86%, respectively. Increased catechol-O-methyltransferase immunoreactivity was located primarily into the activated microglial cells in the lesion area. Interestingly, catechol-O-methyltransferase and OX-42 stained also intensively microglia/macrophage-like cells which surrounded the adjacent blood vessels. Inhibition of catechol-O-methyltransferase activity by tolcapone or entacapone did not increase lipopolysaccharide-induced neurotoxicity. We conclude that catechol-O-methyltransferase activity and protein expression were increased in the substantia nigra after inflammation induced by lipopolysaccharides. These changes in glial and perivascular catechol-O-methyltransferase activity may have clinical relevance for Parkinson's disease drug treatment due to increased metabolism of levodopa in the brain.
Insights
In Parkinson's disease models, inflammation increases catechol-O-methyltransferase (COMT) in the substantia nigra. This glial COMT activity may affect levodopa metabolism, impacting Parkinson's disease treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Activated microglia are implicated in Parkinson's disease pathology.
- Catechol-O-methyltransferase (COMT) activity may elevate during neuroinflammation.
- Lipopolysaccharides (LPS) are potent microglial activators.
Purpose of the Study:
- To investigate the effect of LPS-induced inflammation on COMT activity and expression in the nigrostriatal pathway.
- To determine the cellular localization of increased COMT.
- To assess the impact of COMT inhibition on LPS-induced neurotoxicity.
Main Methods:
- Paranigral LPS infusion in rats.
- Measurement of COMT activity and protein levels (Western blot).
- Immunohistochemistry for COMT, OX-42 (microglial marker).
- Administration of COMT inhibitors (tolcapone, entacapone).
Main Results:
- LPS induced microglial activation and delayed injury to the nigrostriatal pathway.
- COMT activity in the substantia nigra increased by 213%.
- Soluble and membrane-bound COMT protein levels rose by 255% and 86%, respectively.
- Increased COMT immunoreactivity was observed in activated microglia and perivascular cells.
- COMT inhibition did not exacerbate LPS-induced neurotoxicity.
Conclusions:
- LPS-induced inflammation significantly increases COMT activity and protein expression in the substantia nigra.
- Activated glial cells and perivascular cells are primary sites of elevated COMT.
- These inflammatory changes in COMT may influence levodopa metabolism in Parkinson's disease, potentially affecting therapeutic efficacy.
