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

• Published in: Journal of the neurological sciences Vol. 334; no. 1-2; pp. 18 - 23
• Main Authors: Spitsin, Sergei, Stevens, Kathleen E., Douglas, Steven D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2013
• Subjects: Adult; AIDS-Associated Nephropathy - cerebrospinal fluid; AIDS-Associated Nephropathy - genetics; AIDS-Associated Nephropathy - immunology; AIDS-Associated Nephropathy - pathology; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Biomarkers - cerebrospinal fluid; Biomarkers - metabolism; Brain; CD163 Antigen; Female; Frontal Lobe - immunology; Frontal Lobe - metabolism; Frontal Lobe - pathology; Gene Expression Profiling; Gene Expression Regulation; HIV; HIVE; Human immunodeficiency virus; Humans; Male; Middle Aged; Neurokinin-1 receptor; Neurology; Neuropathology; Receptors, Cell Surface - metabolism; Receptors, Neurokinin-1 - biosynthesis; Substance P; Substance P - biosynthesis; Viral Load; HIVE; Brain; Neurokinin-1 receptor; HIV; Substance P; Neuropathology
• ISSN: 0022-510X; 1878-5883; 1878-5883
• DOI: 10.1016/j.jns.2013.07.008

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.