Identification by mRNA differential display of two up-regulated genes as candidate mediators of AIDS dementia.

BACKGROUND

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 = 7) and without (n = 8) cognitive impairment as well as from HIV-1 seronegative controls (n = 4).

RESULTS

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).

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.