Frontiers in Neuroscience (Sep 2018)
CuII(atsm) Attenuates Neuroinflammation
- Xin Yi Choo,
- Xin Yi Choo,
- Xin Yi Choo,
- Jeffrey R. Liddell,
- Jeffrey R. Liddell,
- Mikko T. Huuskonen,
- Alexandra Grubman,
- Alexandra Grubman,
- Alexandra Grubman,
- Diane Moujalled,
- Jessica Roberts,
- Kai Kysenius,
- Kai Kysenius,
- Lauren Patten,
- Hazel Quek,
- Lotta E. Oikari,
- Clare Duncan,
- Simon A. James,
- Simon A. James,
- Lachlan E. McInnes,
- David J. Hayne,
- Paul S. Donnelly,
- Eveliina Pollari,
- Suvi Vähätalo,
- Katarína Lejavová,
- Mikko I. Kettunen,
- Tarja Malm,
- Jari Koistinaho,
- Jari Koistinaho,
- Anthony R. White,
- Anthony R. White,
- Katja M. Kanninen,
- Katja M. Kanninen
Affiliations
- Xin Yi Choo
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Xin Yi Choo
- Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia
- Xin Yi Choo
- Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, VIC, Australia
- Jeffrey R. Liddell
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Jeffrey R. Liddell
- Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, VIC, Australia
- Mikko T. Huuskonen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- Alexandra Grubman
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Alexandra Grubman
- Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia
- Alexandra Grubman
- Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
- Diane Moujalled
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Jessica Roberts
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Kai Kysenius
- Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, VIC, Australia
- Kai Kysenius
- Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
- Lauren Patten
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Hazel Quek
- Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Lotta E. Oikari
- Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Clare Duncan
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Simon A. James
- Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
- Simon A. James
- Australian Synchrotron, Clayton, VIC, Australia
- Lachlan E. McInnes
- School of Chemistry, Bio21 Institute for Molecular Science and Biotechnology, The University of Melbourne, Melbourne, VIC, Australia
- David J. Hayne
- School of Chemistry, Bio21 Institute for Molecular Science and Biotechnology, The University of Melbourne, Melbourne, VIC, Australia
- Paul S. Donnelly
- School of Chemistry, Bio21 Institute for Molecular Science and Biotechnology, The University of Melbourne, Melbourne, VIC, Australia
- Eveliina Pollari
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- Suvi Vähätalo
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- Katarína Lejavová
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- Mikko I. Kettunen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- Tarja Malm
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- Jari Koistinaho
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- Jari Koistinaho
- Neuroscience Center, University of Helsinki, Helsinki, Finland
- Anthony R. White
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Anthony R. White
- Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Katja M. Kanninen
- Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia
- Katja M. Kanninen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- DOI
- https://doi.org/10.3389/fnins.2018.00668
- Journal volume & issue
-
Vol. 12
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 CuII(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 CuII(atsm) in reducing acute cerebrovascular inflammation caused by peripheral administration of bacterial lipopolysaccharide (LPS). CuII(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 CuII(atsm) on the neuroimmune system suggest copper complexes are potential therapeutics for the treatment of neuroinflammatory conditions.
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