Abstract
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.
Keywords
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Article info
Publication history
Published online: August 05, 2013
Accepted:
July 11,
2013
Received in revised form:
July 9,
2013
Received:
April 29,
2013
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
