Research Article| Volume 334, ISSUE 1-2, P18-23, November 15, 2013

Expression of substance P, neurokinin-1 receptor and immune markers in the brains of individuals with HIV-associated neuropathology

  • Sergei Spitsin
    Division of Allergy and Immunology, Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
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  • Author Footnotes
    1 K.E.S. is currently at W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
    Kathleen E. Stevens
    1 K.E.S. is currently at W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
    Division of Allergy and Immunology, Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
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  • Steven D. Douglas
    Corresponding author at: Division of Allergy and Immunology, The Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd. ARC 1211, Philadelphia, PA 19104. Tel.: +1 215 590 1978; fax: +1 215 590 3044.
    Division of Allergy and Immunology, Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, USA

    Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Author Footnotes
    1 K.E.S. is currently at W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
Published:August 05, 2013DOI:


      The tachykinin neuropeptide substance P (SP) has an important signaling role in both the nervous and the immune systems. Two naturally occurring variants of the neurokinin-1 receptor (NK1R) mediate the effects of SP, full-length receptor (NK1R-F) and a truncated form (NK1R-T) that lacks 96 amino acid residues at the C-terminus. We previously reported decreased expression of the NK1R-F in the CNS of HIV-positive individuals in comparison to HIV-negative control subjects. There were no differences in the expression of the NK1R-T in the same groups. In the current study, we quantified the expressions of SP precursor mRNA preprotachykinin (TAC1), NK1R (full and truncated forms), viral load (HIV-gag) and several proinflammatory and immune markers (CD4, CCR5, CXCR4, fractalkine, IL-6, IL-10, CCL2, CCL20 and CD163) in the frontal cortex of autopsied brains from HIV-1-positive individuals with or without HIV-associated neuropathology. The expressions of SP and, to lesser extent, NK1R-F were decreased while the expressions of CXCR4, CCR5 and CCL2 were increased in CNS of individuals with HIV-associated neuropathology. There was no change in HIV loads associated with neuropathology; however, we found a positive correlation between viral loads and the expression of haptoglobin–hemoglobin scavenger receptor CD163. An analysis of CSF from corresponding samples demonstrated an increase in proinflammatory markers (CCL2 MIP-1α and MIP-1β) associated with neuropathology. Although our data confirm the overall inflammatory nature of HIV-associated neuropathology, we observed a decrease in the expression of SP and NK1R-F, which is also associated with other forms of neuroinflammation.


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