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Int. J. Mol. Sci. 2015, 16(7), 15150-15171; doi:10.3390/ijms160715150

Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE)

1
Lundbeck Research USA, Paramus, NJ 07652, USA
2
Translational Neuropsychiatry Unit, Aarhus University, Risskov DK-8240, Denmark
3
Behavioral Core Facility, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Chak-Sing Lau
Received: 28 April 2015 / Revised: 11 June 2015 / Accepted: 24 June 2015 / Published: 3 July 2015
View Full-Text   |   Download PDF [1641 KB, uploaded 3 July 2015]   |  

Abstract

Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction is evident before significant levels of autoantibody titers and nephritis are present. We examined the behavioral profile of MRL/lpr mice and their congenic controls, a comprehensive plasma cytokine and chemokine profile, and brain levels of serotonin and kynurenine pathway metabolites. Consistent with previous studies, MRL/lpr mice had increased depression-like behavior and visuospatial memory impairment. Plasma levels of different inflammatory molecules (Haptoglobin, interleukin 10 (IL-10), interferon γ-inducible protein 10 (IP-10/CXCL10), lymphotactin, macrophage inhibitory protein 3β (MIP-3β/CCL19), monocyte chemotactic protein 1, 3 and 5 (MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12), vascular cell adhesion molecule 1 (VCAM-1), lymphotactin and interferon γ (IFN-γ)) were increased in MRL/lpr mice. In cortex and hippocampus, MRL/lpr mice had increased levels of kynurenine pathway metabolites (kynurenine, 3-hydroxykynurenine, 3-hydroxynthranilic acid and quinolinic acid). Therefore, our study suggests that increased cytokine expression may be critical in the regulation subtle aspects of brain function in NP-SLE via induction of IDO and tryptophan/kynurenine metabolism. View Full-Text
Keywords: MRL/lpr; lupus; forced swim test; anhedonia; novel object placement test; cytokines; chemokines; indoleamine-2,3-dioxygenase (IDO); kynurenine MRL/lpr; lupus; forced swim test; anhedonia; novel object placement test; cytokines; chemokines; indoleamine-2,3-dioxygenase (IDO); kynurenine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, Y.; Eskelund, A.R.; Zhou, H.; Budac, D.P.; Sánchez, C.; Gulinello, M. Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE). Int. J. Mol. Sci. 2015, 16, 15150-15171.

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