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

Background: In the dementia associated with acquired immunodeficiency syndr ome (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 o f human immunodeficiency virus type 1 (HIV-1)-induced neurotoxicity in vivo we have adapted the mRNA differential display technique to monitor the gen e expression pattern in postmortem cortical tissue from AIDS patients with (n = 7) and without (n = 8) cognitive impairment as well as from HIV-1 sero negative controls (M = 4). Results: Out of 29 differentially expressed cDNAs, two cDNA clones had conf irmed variation of transcriptional regulation as assessed by reverse Northe rn analysis and gene-specific reverse transcription polymerase chain reacti on (RT-PCR) and were up-regulated in the cortex of patients with AIDS demen tia. Nucleotide sequence analysis of the two cDNAs identified known genes n ot previously associated with the pathogenesis of AIDS dementia, including the neurotrophin receptor tyrosine kinase receptor B (TrkB) and the potassi um channel human open rectifyer K+ channel (ORK) homologous open reading fr ame (HOHO1). Conclusions: The altered expression of these transcripts may contribute to AIDS dementia through the enhancement of microglial activation and immunolo gic nitric oxide synthase (iNOS) activity by abnormal neurotrophic regulati on and interference with membrane excitability through disturbance of local ion homeostasis.