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Increased catechol-O-methyltransferase activity and protein expression in OX-42-positive cells in the substantia nigra after lipopolysaccharide microinfusion

Helkamaa, Teemu; Reenilä, Ilkka; Tuominen, Raimo K.; Soinila, Seppo; Väänänen, Antti; Tilgmann, Carola LU and Rauhala, Pekka (2007) In Neurochemistry International 51(6-7). p.412-423
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... (More)

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. © 2007 Elsevier Ltd. All rights reserved.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Catechol-O-methyltransferase, Dopamine, l-Dopa, Lipopolysaccharide, Microglia, OX-42, Parkinson's disease, Substantia nigra
in
Neurochemistry International
volume
51
issue
6-7
pages
12 pages
publisher
Elsevier
external identifiers
  • Scopus:34848926047
ISSN
0197-0186
DOI
10.1016/j.neuint.2007.04.020
language
English
LU publication?
no
id
ba97efe1-85b1-4e65-a47b-4c07ebbe71cd
date added to LUP
2016-04-11 13:04:33
date last changed
2016-11-13 04:38:29
@misc{ba97efe1-85b1-4e65-a47b-4c07ebbe71cd,
  abstract     = {<p>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. © 2007 Elsevier Ltd. All rights reserved.</p>},
  author       = {Helkamaa, Teemu and Reenilä, Ilkka and Tuominen, Raimo K. and Soinila, Seppo and Väänänen, Antti and Tilgmann, Carola and Rauhala, Pekka},
  issn         = {0197-0186},
  keyword      = {Catechol-O-methyltransferase,Dopamine,l-Dopa,Lipopolysaccharide,Microglia,OX-42,Parkinson's disease,Substantia nigra},
  language     = {eng},
  number       = {6-7},
  pages        = {412--423},
  publisher    = {ARRAY(0x9e692c8)},
  series       = {Neurochemistry International},
  title        = {Increased catechol-O-methyltransferase activity and protein expression in OX-42-positive cells in the substantia nigra after lipopolysaccharide microinfusion},
  url          = {http://dx.doi.org/10.1016/j.neuint.2007.04.020},
  volume       = {51},
  year         = {2007},
}