| Publication Abstract Display | | Type: Published Abstract | | Title: NNTC gene array reveals brain adaptations and two different kinds of HIV-associated neurocognitive disorder. | | Authors: Gelman B, Chen T, Soukup V, Starkey J, Masliah E, Commins D, Brandt D, Singer E, Grant I, S Morgello | | Year: 2010 | | Publication: 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA | | Volume: Issue: Pages: | | Abstract:Background: The National NeuroAIDS Tissue Consortium (NNTC) performed a brain gene expression array on subjects with HIV-associated neurocognitive disorders (HAND). Demented subjects with and without HIV encephalitis (HIVE) were examined, as were infected subjects without any impairment.
Methods: The Affymetrix® gene array platform was used to examine the frontal neocortex, neostriatum, and frontal white matter.
Results: HAND with, and without HIVE appeared virtually identical to each other with respect to neurocognitive test responses. But neurochemically, the 2 demented groups were completely different. With HIVE, HIV RNA load in brain tissue was 4 log units higher relative to the group of demented subjects without HIVE. With HIVE, over 1,900 probes were regulated, including increased interferon response genes, antigen presentation, complement components, and CD163 antigen. Immune responses were especially strong in neostriatum, whereas downregulated neuronally expressed pathways were selective for neocortex. Neocortical changes included GABA receptors, glutamate receptor signaling, synaptic long term potentiation, axon guidance, clathrin-mediated endocytic pathways. In contrast, HAND without HIVE had just 92-regulated transcripts. There were abnormally weak brain immune responses, including CD163; down-regulated neocortical neuronal responses were lacking; there was prominent regulation of transcripts uniquely expressed in endothelial cells. In HIV-1-infected subjects without dementia there were mild immunological responses and neuronal adaptations that could be detected only in neostriatum.
Conclusions: Three patterns of gene expression are noted: 1) Type I HAND is linked closely to high brain HIV-1 loads and HIVE, provokes strong immune responses in brain and regulates neocortical neurons. 2) Type II HAND is not linked to brain HIV-1 load or HIVE, exhibits relatively weak neuroimmune responses, and has a reticuloendothelial connection. 3) HIV-1-infected people with normal neurocognitive function harbor subtle shifts in neostriatal gene expression that relate to compensatory or adaptive changes. |
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