Cu-II(atsm) Attenuates Neuroinflammation

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Choo , X Y , Liddell , J R , Huuskonen , M T , Grubman , A , Moujalled , D , Roberts , J , Kysenius , K , Patten , L , Quek , H , Oikari , L E , Duncan , C , James , S A , McInnes , L E , Hayne , D J , Donnelly , P S , Pollari , E , Vähätalo , S , Lejavova , K , Kettunen , M , Malm , T , Koistinaho , J , White , A R & Kanninen , K M 2018 , ' Cu-II(atsm) Attenuates Neuroinflammation ' , Frontiers in Neuroscience , vol. 12 , 668 . https://doi.org/10.3389/fnins.2018.00668

Title: Cu-II(atsm) Attenuates Neuroinflammation
Author: Choo, Xin Yi; Liddell, Jeffrey R.; Huuskonen, Mikko T.; Grubman, Alexandra; Moujalled, Diane; Roberts, Jessica; Kysenius, Kai; Patten, Lauren; Quek, Hazel; Oikari, Lotta E.; Duncan, Clare; James, Simon A.; McInnes, Lachlan E.; Hayne, David J.; Donnelly, Paul S.; Pollari, Eveliina; Vähätalo, Suvi; Lejavova, Katarina; Kettunen, Mikko; Malm, Tarja; Koistinaho, Jari; White, Anthony R.; Kanninen, Katja M.
Contributor: University of Helsinki, Neuroscience Center
Date: 2018-09-24
Language: eng
Number of pages: 14
Belongs to series: Frontiers in Neuroscience
ISSN: 1662-453X
URI: http://hdl.handle.net/10138/248084
Abstract: Background: Neuroinflammation and biometal dyshomeostasis are key pathological features of several neurodegenerative diseases, including Alzheimer's disease (AD). Inflammation and biometals are linked at the molecular level through regulation of metal buffering proteins such as the metallothioneins. Even though the molecular connections between metals and inflammation have been demonstrated, little information exists on the effect of copper modulation on brain inflammation. Methods: We demonstrate the immunomodulatory potential of the copper bis(thiosemicarbazone) complex Cu-II(atsm) in an neuroinflammatory model in vivo and describe its anti-inflammatory effects on microglia and astrocytes in vitro. Results: By using a sophisticated in vivo magnetic resonance imaging (MRI) approach, we report the efficacy of Cu-II(atsm) in reducing acute cerebrovascular inflammation caused by peripheral administration of bacterial lipopolysaccharide (LPS). Cu-II(atsm) also induced anti-inflammatory outcomes in primary microglia [significant reductions in nitric oxide (NO), monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor (TNF)] and astrocytes [significantly reduced NO, MCP-1, and interleukin 6 (IL-6)] in vitro. These anti-inflammatory actions were associated with increased cellular copper levels and increased the neuroprotective protein metallothionein-1 (MT1) in microglia and astrocytes. Conclusion: The beneficial effects of Cu-II(atsm) on the neuroimmune system suggest copper complexes are potential therapeutics for the treatment of neuroinflammatory conditions.
Subject: microglia
astrocyte
inflammation
neurodegeneration
copper
AMYOTROPHIC-LATERAL-SCLEROSIS
PLASMA-MASS SPECTROMETRY
METALLOTHIONEIN GENE-EXPRESSION
AMYLOID-BETA PEPTIDE
ALZHEIMERS-DISEASE
MOUSE MODEL
MICROGLIAL ACTIVATION
ANIMAL-MODELS
IN-VIVO
INFLAMMATORY RESPONSES
3112 Neurosciences
3124 Neurology and psychiatry
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