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HIV-1 Tat activates indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures in a p38 mitogen-activated protein kinase-dependent manner by Xin Fu; Marcus A Lawson; Keith W Kelley; Robert Dantzer is a Neuroscience article available to read on EtoBox.

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## Background We have established that activation of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO) mediates the switch from cytokine-induced sickness behavior to depressive-like behavior. Because human immunodeficiency virus type 1 (HIV-1) Tat protein causes depressive-like behavior in mice, we investigated its ability to activate IDO in organotypic hippocampal slice cultures (OHSCs) derived from neonatal C57BL/6 mice. ## Methods Depressive-like behavior in C57BL/6J mice was assessed by the forced swim test. Expression of cytokines and IDO mRNA in OHSCs was measured by real-time RT-PCR and cytokine protein was measured by enzyme-linked immunosorbent assays (ELISAs). p38 MAPK phosphorylation was analyzed by western blot. ## Results Intracerebroventricular (__i.c.v__.) administration of Tat (40 ng) induced depressive-like behavior in the absence of sickness. Addition of Tat (40 ng/slice) to the medium of OHSCs induced IDO steady-state mRNA that peaked at 6 h. This effect was potentiated by pretreatment with IFNγ. Tat also induced the synthesis and release of TNFα and IL-6 protein in the supernatant of the slices and increased expression of the inducible isoform of

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Author

Xin Fu; Marcus A Lawson; Keith W Kelley; Robert Dantzer

Publisher

BioMed Central; Springer (Biomed Central Ltd.); [London]: BioMed Central, c2004-; Springer Science and Business Media LLC; Society for Mining, Metallurgy and Exploration Inc. (ISSN 1742-2094)

Published

2011

Language

EN

Field

Neuroscience (Life Sciences)