Paper Report for: Ekins_2017_AIDS_31_1083

OBJECTIVE: The study set out to determine if the HIV protease inhibitor, indinavir, alters responsiveness of alpha7-nicotinic acetylcholine receptors to acetylcholine. DESIGN: Treatment with HAART has dramatically reduced development of HIV-associated dementia and more severe forms of cognitive impairment. However, many individuals continue to experience cognitive decline of uncertain cause. Previous studies have failed to demonstrate significant alterations of functional brain connectivity, structural brain changes, or changes in cerebral blood flow sufficient to explain cognitive decline in virally suppressed individuals. This suggests that the mechanisms underlying development and progression of cognitive problems likely occurs at a micro rather than macro level, such as disruptions in neurotransmitter system signaling. MATERIALS AND
METHODS: Indinavir's effects on alpha7-nicotinic acetylcholine receptor activity was tested using a ScreenPatch IonWorks Barracuda-based assay in a mammalian cell model.
RESULTS: At low concentrations (0.0003-10 mumol/l) indinavir acts as a positive allosteric modulator (EC50 = 0.021 mumol/l), whereas at concentrations greater than 10 mumol/l (30-100 mumol/l) indinavir acts as an inhibitor of the alpha7-nicotinic acetylcholine receptor. CONCLUSION: At concentrations greater than 10 mumol/l indinavir reduces synaptic transmission in the acetylcholine neurotransmitter system, which could possibly contribute to cognitive dysfunction. These results suggest that further experiments should be considered to assess whether patients might benefit from treatment with cholinesterase inhibitors that counteract the effects of indinavir.