posted on 2024-01-30, 13:41authored byCory J. White, Andrew M. Gausepohl, Hannah N. Wilkins, Colten D. Eberhard, Benjamin C. Orsburn, Dionna W. Williams
Human immunodeficiency virus (HIV) infection continues
to promote
neurocognitive impairment, mood disorders, and brain atrophy, even
in the modern era of viral suppression. Brain lipids are vulnerable
to HIV-associated energetic strain and may contribute to HIV-associated
neurologic dysfunction due to alterations in lipid breakdown and structural
lipid composition. HIV neuropathology is region dependent, yet there
has not been comprehensive characterization of the spatial heterogeneity
of brain lipids during infection that possibly impacts neurologic
function. To address this gap, we evaluated the spatial lipid distribution
using matrix laser desorption/ionization imaging mass spectrometry
(MALDI-IMS) across four brain regions (parietal cortex, midbrain,
thalamus, and temporal cortex), as well as the kidney for a peripheral
tissue control, in a simian immunodeficiency virus (SIV)-infected
rhesus macaque treated with a course of antiretroviral therapies (ARTs).
We assessed lipids indicative of fat breakdown [acylcarnitines (CARs)]
and critical structural lipids [phosphatidylcholines (PCs) and phosphatidylethanolamines
(PEs)] across fatty acid chain lengths and degrees of unsaturation.
CARs with very long-chain, polyunsaturated fatty acids (PUFAs) were
more abundant across all brain regions than shorter chain, saturated,
or monounsaturated species. We observed distinct brain lipid distribution
patterns for the CARs and PCs. However, no clear expression patterns
emerged for PEs. Surprisingly, the kidney was nearly devoid of ions
corresponding to PUFAs common in brain. PEs and PCs with PUFAs had
little intensity and less density than other species, and only one
CAR species was observed in kidney at high intensity. Overall, our
study demonstrates the stark variation in structural phospholipids
and lipid-energetic intermediates present in the virally suppressed
SIV-macaque brain. These findings may be useful for identifying regional
vulnerabilities to damage due to brain lipid changes in people with
HIV.