Mitochondrial redox environments predict sensorimotor brain-behavior dynamics in adults with HIV

Area of Science:

• Neuroscience
• Mitochondrial Biology
• HIV Research

Background:

• People living with HIV (PLWH) often experience cognitive impairment, particularly motor control deficits, even with viral suppression.
• The molecular mechanisms underlying HIV-related motor dysfunction, especially the role of mitochondrial function, are not well understood.

Purpose of the Study:

• To investigate the relationship between the mitochondrial redox environment and sensorimotor brain-behavior dynamics in virally suppressed PLWH.
• To compare these relationships in PLWH with demographically matched controls.

Main Methods:

• Utilized Seahorse Analyzer for mitochondrial function, electron paramagnetic resonance spectroscopy for superoxide levels, antioxidant assays, and dynamic magnetoencephalography (MEG) for sensorimotor oscillations.
• Employed structural equation modeling to analyze predictive capacities and mediation analyses to explore pathways.

Main Results:

• In PLWH, sensorimotor brain-behavior relationships were differentially modulated by superoxide and hydrogen peroxide-sensitive redox features.
• In controls, only superoxide-sensitive redox features correlated with optimal oscillatory responses and better motor performance.
• Mediation analyses indicated distinct mechanisms of action within the redox environment in PLWH.

Conclusions:

• Mitochondrial redox parameters significantly modulate sensorimotor oscillations and behavior in both healthy individuals and PLWH.
• Aberrant redox pathways in PLWH contribute to motor control deficits.
• Mitochondrial redox parameters represent potential therapeutic targets for mitigating HIV-associated cognitive-motor dysfunction.