Distilled database identifies genetic links to rare diseases
24 March 2023
Published online 21 March 2013
During HIV infection, the virus supresses enzymes in the brain that help make important steroids, according to a new study published in FASEB Journal. A course of steroid treatment could, the authors suggest, alleviate the brain inflammation and cognitive deficits experienced by people living with HIV.
Christopher Power of the University of Alberta in in Edmonton, Canada and his colleagues, including Samir Ahboucha of the Université Cadi Ayyad in Marrakech, Morocco, examined the brain tissue of seven people who had succumbed to AIDS, and compared it to tissue samples from seven controls who had died of other causes.
Using antibody staining, they found much lower levels of enzymes that catalyze the synthesis of the neuroactive steroids dehydroepiandrosterone (DHEA) and pregnenalone — two common endogenous steroid hormones — in those who were HIV-infected.
During HIV infection, the expression of proinflammatory genes in the brain is thought to contribute to the death of neurons. However, the team found that administering sulfated DHEA suppressed proinflammatory gene expression in FIV-infected cats, an animal model of HIV infection, and that this was accompanied by reduced neuropathology and cognitive and behavioural deficits.
The findings suggest that DHEA and other steroids can modulate the immune system in the brain, and could be used to alleviate the neurocognitive symptoms associated with HIV.
"We are testing other neurosteroids in this model and others," says Power. "I doubt sulfated DHEA will go to clinical trials but we might go forward with related compounds."