HIV-1 Tat activates indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures in a p38 mitogen-activated protein kinase-dependent manner
2011

HIV-1 Tat Protein and Its Role in Depression

Sample size: 6 publication 10 minutes Evidence: moderate

Author Information

Author(s): Fu Xin, Lawson Marcus A, Kelley Keith W, Dantzer Robert

Primary Institution: University of Illinois at Urbana-Champaign

Hypothesis

Does HIV-1 Tat protein activate indoleamine 2,3 dioxygenase (IDO) in the brain, leading to depressive-like behavior?

Conclusion

HIV-1 Tat induces IDO expression through a mechanism that depends on p38 MAPK activation, which may contribute to depressive disorders in HIV-infected patients.

Supporting Evidence

  • HIV-1 Tat administration increased immobility in the forced swim test, indicating depressive-like behavior.
  • Tat induced IDO expression in organotypic hippocampal slice cultures.
  • The effect of Tat on IDO expression was mediated by p38 MAPK activation.
  • Proinflammatory cytokines TNFα and IL-6 were also increased in response to Tat treatment.

Takeaway

The HIV-1 Tat protein can make mice feel sad without making them sick, and it does this by changing how certain brain chemicals work.

Methodology

Mice were treated with HIV-1 Tat and assessed for depressive-like behavior using the forced swim test, while organotypic hippocampal slice cultures were used to measure IDO expression and cytokine levels.

Participant Demographics

12-week-old male C57BL/6J mice

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1742-2094-8-88

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