Elevated Galectin-9 across the human brain correlates with HIV neuropathology and detrimental cognitive states.
Title | Elevated Galectin-9 across the human brain correlates with HIV neuropathology and detrimental cognitive states. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Premeaux, TA, Yeung, ST, Pillai, SK, Ndhlovu, LC |
Journal | J Neurovirol |
Volume | 29 |
Issue | 3 |
Pagination | 337-345 |
Date Published | 2023 Jun |
ISSN | 1538-2443 |
Keywords | Brain, Cognition, Galectins, HIV Infections, Humans |
Abstract | HIV persistence and neuroinflammation are known to contribute to HIV-associated neuropathology. However, the multifaceted pathways driving impairment remain poorly understood. Galectin-glycan interactions have emerged as significant contributors to neuroinflammatory processes and may play a role in neuroHIV. Here, we quantified Galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, in post-mortem brain tissue across multiple regions from HIV-infected and HIV-uninfected donors to determine causal associations with HIV brain injury. We demonstrate that the staining intensity, total staining area, and cell-associated frequency of Gal-9 were elevated, principally in the frontal lobe and basal ganglia. Higher frontal lobe Gal-9 levels correlated with lower pre-mortem neuropsychological performance test scores in areas of attention and motor skills. Our results suggest that Gal-9 activity across the brain plays a role in neuroHIV pathogenesis and constitutes a promising disease-modifying target. |
DOI | 10.1007/s13365-023-01149-9 |
Alternate Journal | J Neurovirol |
PubMed ID | 37233903 |
PubMed Central ID | 5426376 |
Grant List | R01 MH112457 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States U24 MH100929 / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States U24 MH100925 / MH / NIMH NIH HHS / United States |