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Cull(atsm) attenuates neuroinflammation

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, Lejavová, Katarina, Kettunen, Mikki I. and Malm, Tarja 2018, Cull(atsm) attenuates neuroinflammation, Frontiers in neuroscience, vol. 12, pp. 1-14, doi: 10.3389/fnins.2018.00668.

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Title Cull(atsm) attenuates neuroinflammation
Author(s) 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.ORCID iD for Hayne, David J. orcid.org/0000-0003-2756-9427
Donnelly, Paul S.
Pollari, Eveliina
Vähätalo, Suvi
Lejavová, Katarina
Kettunen, Mikki I.
Malm, Tarja
Journal name Frontiers in neuroscience
Volume number 12
Article ID 668
Start page 1
End page 14
Total pages 14
Publisher Frontiers
Place of publication Lausanne, Switzerland
Publication date 2018-09-24
ISSN 1662-4548
1662-453X
Keyword(s) microglia
astrocyte
inflammation
neurodegeneration
copper
Summary 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.
Language eng
DOI 10.3389/fnins.2018.00668
Field of Research 1109 Neurosciences
1702 Cognitive Science
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, Choo, Liddell, Huuskonen, Grubman, Moujalled, Roberts, Kysenius, Patten, Quek, Oikari, Duncan, James, McInnes, Hayne, Donnelly, Pollari, Vähätalo, Lejavová, Kettunen, Malm, Koistinaho, White and Kanninen
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30115739

Document type: Journal Article
Collections: Institute for Frontier Materials
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.