Abstract
We analyzed RNA gene expression in neurons from 16 cases in four categories, HIV associated dementia with HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and HIV-1-positive (HIV+)with neither HAD nor HIVE. We produced the neurons by laser capture microdissection (LCM) from cryopreserved globus pallidus. Of 55,000 gene fragments analyzed, expression of 197 genes was identified with significance (p = 0.005).We examined each gene for its position in the human genome and found a non-stochastic occurrence for only seven genes, on chromosome 22. Six of the seven genes were identified, CSNK1E (casein kinase 1 epsilon), DGCR8 (Di George syndrome critical region 8), GGA1 (Golgi associated gamma adaptin ear containing ARF binding protein 1), MAPK11 (mitogen activated protein kinase 11), SMCR7L (Smith-Magenis syndrome chromosome region candidate 7-like), andTBC1D22A (TBC1 domain family member 22A). Six genes (CSNK1E, DGCR8, GGA1, MAPK11, SMCR7L, and one unidentified gene) had similar expression profiles across HAD/HIVE, HAD, and HIVE vs. HIV+ whereas one gene (TBC1D22A) had a differing gene expression profile across these patient categories. There are several mental disease-related genes including miRNAs on chromosome 22 and two of the genes (DGCR8 and SMCR7L) identified here are mental disease-related. We speculate that dysregulation of gene expression may occur through mechanisms involving chromatin damage and remodeling. We conclude that the pathogenesis of NeuroAIDS involves dysregulation of expression of mental disease-related genes on chromosome 22 as well as additional genes on other chromosomes. The involvement of these genes as well as miRNA requires additional investigation since numerous genes appear to be involved.
Highlights
NeuroAIDS and HIV associated dementia (HAD): The involvement of the CNS in HIV-related disease generally has been termed NeuroAIDS
Chromosome 22 demonstrated a nonstochastic number of ascribed genes (p ≤ 0.0001).Six genes identified on chromosome 22 are CSNK1E, DGCR8 (Di George syndrome critical region 8), GGA1 (Golgi associated gamma adapt in ear containing ARF binding protein 1), MAPK11, SMCR7L (Smith-Magenis syndrome chromosome region candidate 7like), andTBC1D22A (TBC1 domain family member 22A)
Conclusions and future directions: Two of seven genes that show changes in expression on chromosome 22 are involved in mental disease and may be involved in the pathogenesis of HAD and HIV encephalitis (HIVE)
Summary
NeuroAIDS and HAD: The involvement of the CNS in HIV-related disease generally has been termed NeuroAIDS. HIV associated dementia (HAD) and minor cognitive motor disorder (MCMD) were terms used as well. The presence of infiltrating macrophages and activated microglial containing HIV-1, termed HIV encephalitis (HIVE) is part of the neuropathological substrate of this disease. Since the advent of HAART, a new term, HIV-associated neurocognitive disorders (HAND) has come to the fore. Due to HAART, the incidence of motor abnormalities and cognitive impairment of HAD and HIVE decreased their prevalence has increased. Factors possibly associated with these changes may include viral mutations and patient longevity [3, 4, 5]. In the results reported here, the patients are from studies in an earlier time-period, prior to the implementation of HAND as a diagnostic entity [6]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have