Abstract
In the dementia associated with acquired immunodeficiency syndrome (AIDS), indirect pathomechanisms are important mediators of progressive neuronal injury and variable candidate molecules of potential pathogenetic importance have been identified. In an attempt to characterize additional mediators of human immunodeficiency virus type 1 (HIV-1)-induced neurotoxicity in vivo we have adapted the mRNA differential display technique to monitor the gene expression pattern in postmortem cortical tissue from AIDS patients with (n = 7) and without (n = 8) cognitive impairment as well as from HIV-1 seronegative controls (n = 4). Out of 29 differentially expressed cDNAs, two cDNA clones had confirmed variation of transcriptional regulation as assessed by reverse Northern analysis and gene-specific reverse transcription polymerase chain reaction (RT-PCR) and were up-regulated in the cortex of patients with AIDS dementia. Nucleotide sequence analysis of the two cDNAs identified known genes not previously associated with the pathogenesis of AIDS dementia, including the neurotrophin receptor tyrosine kinase receptor B (TrkB) and the potassium channel human open rectifyer K+ channel (ORK) homologous open reading frame (HOHO1). The altered expression of these transcripts may contribute to AIDS dementia through the enhancement of microglial activation and immunologic nitric oxide synthase (iNOS) activity by abnormal neurotrophic regulation and interference with membrane excitability through disturbance of local ion homeostasis.
Highlights
The pathogenesis of the dementia associated with the acquired immunodeficiency syndrome (AIDS) is incompletely elucidated
We identified 29 PCR products that were differentially expressed between brain tissues obtained from severely demented and nondemented AIDS patients or normal controls
Using the mRNA differential display technique and 77 primer combinations, we identified 29 cDNAs that reproducibly showed different expression patterns between brain tissues from AIDS patients with severe dementia and nondemented AIDS patients or human immunodeficiency virus type 1 (HIV-1) seronegative persons
Summary
The pathogenesis of the dementia associated with the acquired immunodeficiency syndrome (AIDS) is incompletely elucidated. Using reverse transcription polymerase chain reaction (RTPCR)-based mRNA differential display [11,12,13] we attempted to characterize candidate genes not previously associated with the HIV-1–induced disease process in the brain. In the dementia associated with acquired immunodeficiency syndrome (AIDS), indirect pathomechanisms are important mediators of progressive neuronal injury and variable candidate molecules of potential pathogenetic importance have been identified. Materials and Methods: In an attempt to characterize additional mediators of human immunodeficiency virus type 1 (HIV-1)–induced neurotoxicity in vivo we have adapted the mRNA differential display technique to monitor the gene expression pattern in postmortem cortical tissue from AIDS patients with (n ϭ 7) and without (n ϭ 8) cognitive impairment as well as from HIV-1 seronegative controls (n ϭ 4). Conclusions: The altered expression of these transcripts may contribute to AIDS dementia through the enhancement of microglial activation and immunologic nitric oxide synthase (iNOS) activity by abnormal neurotrophic regulation and interference with membrane excitability through disturbance of local ion homeostasis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
