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|Title:||Peripheral Administration of Tumor Necrosis Factor-Alpha Induces Neuroinflammation and Sickness but Not Depressive-Like Behavior in Mice||Authors:||BIESMANS, Steven
Bouwknecht, Jan A.
Ver Donck, Luc
Acton, Paul D.
De Haes, Patrick
|Issue Date:||2015||Publisher:||HINDAWI PUBLISHING CORPORATION||Source:||BIOMED RESEARCH INTERNATIONAL, 2015, (ART N° 716920)||Abstract:||Clinical observations indicate that activation of the TNF-alpha system may contribute to the development of inflammation-associated depression. Here, we tested the hypothesis that systemic upregulation of TNF-alpha induces neuroinflammation and behavioral changes relevant to depression. We report that a single intraperitoneal injection of TNF-alpha in mice increased serum and brain levels of the proinflammatory mediators TNF-alpha, IL-6, and MCP-1, in a dose-and time-dependent manner, but not IL-1 beta. Protein levels of the anti-inflammatory cytokine IL-10 increased in serum but not in the brain. The transient release of immune molecules was followed by glial cell activation as indicated by increased astrocyte activation in bioluminescent Gfap-luc mice and elevated immunoreactivity against the microglial marker Iba1 in the dentate gyrus of TNF-alpha-challenged mice. Additionally, TNF-alpha-injected mice were evaluated in a panel of behavioral tests commonly used to study sickness and depressive-like behavior in rodents. Our behavioral data imply that systemic administration of TNF-alpha induces a strong sickness response characterized by reduced locomotor activity, decreased fluid intake, and body weight loss. Depressive-like behavior could not be separated from sickness at any of the time points studied. Together, these results demonstrate that peripheral TNF-alpha affects the central nervous system at a neuroimmune and behavioral level.||Notes:||[Biesmans, Steven; Davoodi, Nima; Meert, Theo F.; Hellings, Niels] Hasselt Univ, BIOMED, B-3590 Diepenbeek, Belgium. [Biesmans, Steven; Bouwknecht, Jan A.; Donck, Luc Ver; Langlois, Xavier; De Haes, Patrick; Davoodi, Nima; Meert, Theo F.; Nuydens, Rony] Div Janssen Pharmaceut NV, Neurosci Janssen Res & Dev, B-2340 Beerse, Belgium. [Acton, Paul D.] Janssen Res & Dev LLC, Mol Imaging, Spring House, PA 19477 USA.||Document URI:||http://hdl.handle.net/1942/19669||ISSN:||2314-6133||e-ISSN:||2314-6141||DOI:||10.1155/2015/716920||ISI #:||000359236100001||Category:||A1||Type:||Journal Contribution||Validations:||ecoom 2016|
|Appears in Collections:||Research publications|
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