Dolutegravir induces endoplasmic reticulum stress at the blood-brain barrier.

ABSTRACT: Dolutegravir (DTG)-based antiretroviral therapy is the contemporary first-line therapy to treat HIV infection. Despite its efficacy, mounting evidence has suggested a higher risk of neuropsychiatric adverse effect (NPAE) associated with DTG use, with a limited understanding of the underlying mechanisms. Our laboratory has previously reported a toxic effect of DTG but not bictegravir (BTG) in disrupting the blood-brain barrier (BBB) integrity. The current study aimed to investigate the underlying mechanism of DTG toxicity. Primary cultures of mouse brain microvascular endothelial cells were treated with DTG and BTG at therapeutically relevant concentrations. RNA sequencing, qPCR, western blot analysis, and cell stress assays (Ca²⁺ flux, H2DCFDA, TMRE, MTT) were applied to assess

SUBMITTER: Huang C 

PROVIDER: S-EPMC11846018 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature