Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis

Eliezer Masliah, Eleanor S. Roberts, Dianne Langford, Ian Everall, Leslie Crews, Anthony Adame, Edward Rockenstein, Howard S. Fox

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The neurodegenerative process in HIV encephalitis (HIVE) is associated with extensive damage to the dendritic and synaptic structure that often leads to cognitive impairment. Several mechanisms might be at play, including release of neurotoxins, oxidative stress and decreased activity of neurotrophic factors. Furthermore, HIV-mediated dysregulation of genes involved in neuronal maintenance might play an important role. For this purpose, cRNA was prepared from the brains of 17 AIDS patients for analysis with the Affymetrix Human U95Av2 GeneChip and analyzed with the GeneSpring Expression Analysis Software. Out of 12,625 genes analyzed, 74 were downregulated and 59 were upregulated compared to controls. Initial alternative analysis of RNA was performed by ribonuclease protection assay (RPA). In cases with HIVE, downregulated genes included neuronal molecules involved in synaptic plasticity and transmission (ion channels, synaptogyrin, synapsin II), cell cycle (p35, p39, CDC-L2, CDC42, PAK1) and signaling molecules (PI3K, Ras-Raf-MEK1), transcription factors and cytoskeletal components (MAP-1B, MAP-2, tubulin, adducin-2). Upregulated genes included those involved in neuroimmune (IgG, MHC, β2microglobulin) and anti-viral responses (interferon-inducible molecules), transcription (STAT1, OLIG2, Pax-6) and signaling modulation (MEK3, EphB1) of the cytoskeleton (myosin, aduccin-3, radixin, dystrobrevin). Taken together, this study suggests that HIV proteins released from infected macrophages might not only induce a neuroinflammatory response, but also may promote neurodegeneration by interfering with neuronal transcription of genes involved in regulating signaling and cytoskeletal molecules important in maintaining synapto-dendritic functioning and integrity.

Original languageEnglish (US)
Pages (from-to)163-175
Number of pages13
JournalJournal of Neuroimmunology
Volume157
Issue number1-2 SPEC. ISS.
DOIs
StatePublished - Dec 2004

Fingerprint

Frontal Lobe
Encephalitis
HIV
Genes
Synaptogyrins
Down-Regulation
Synapsins
Human Immunodeficiency Virus Proteins
Complementary RNA
Neuronal Plasticity
Nerve Growth Factors
Neurotoxins
Myosins
Tubulin
Centers for Disease Control and Prevention (U.S.)
Ribonucleases
Cytoskeleton
Phosphatidylinositol 3-Kinases
Ion Channels
Synaptic Transmission

Keywords

  • CDK5
  • Gene expression
  • HIVE
  • Interferon

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

Masliah, E., Roberts, E. S., Langford, D., Everall, I., Crews, L., Adame, A., ... Fox, H. S. (2004). Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis. Journal of Neuroimmunology, 157(1-2 SPEC. ISS.), 163-175. https://doi.org/10.1016/j.jneuroim.2004.08.026

Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis. / Masliah, Eliezer; Roberts, Eleanor S.; Langford, Dianne; Everall, Ian; Crews, Leslie; Adame, Anthony; Rockenstein, Edward; Fox, Howard S.

In: Journal of Neuroimmunology, Vol. 157, No. 1-2 SPEC. ISS., 12.2004, p. 163-175.

Research output: Contribution to journalArticle

Masliah, E, Roberts, ES, Langford, D, Everall, I, Crews, L, Adame, A, Rockenstein, E & Fox, HS 2004, 'Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis', Journal of Neuroimmunology, vol. 157, no. 1-2 SPEC. ISS., pp. 163-175. https://doi.org/10.1016/j.jneuroim.2004.08.026
Masliah E, Roberts ES, Langford D, Everall I, Crews L, Adame A et al. Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis. Journal of Neuroimmunology. 2004 Dec;157(1-2 SPEC. ISS.):163-175. https://doi.org/10.1016/j.jneuroim.2004.08.026
Masliah, Eliezer ; Roberts, Eleanor S. ; Langford, Dianne ; Everall, Ian ; Crews, Leslie ; Adame, Anthony ; Rockenstein, Edward ; Fox, Howard S. / Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis. In: Journal of Neuroimmunology. 2004 ; Vol. 157, No. 1-2 SPEC. ISS. pp. 163-175.
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