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

Rachel K. Spooner, Brittany K. Taylor, Iman M. Ahmad, Kelsey Dyball, Katy Emanuel, Jennifer O'Neill, Maureen Kubat, Susan Swindells, Howard S. Fox, Sara H. Bares, Kelly L. Stauch, Matthew C. Zimmerman, Tony W. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

Despite virologic suppression, people living with HIV (PLWH) remain at risk for developing cognitive impairment, with aberrations in motor control being a predominant symptom leading to functional dependencies in later life. While the neuroanatomical bases of motor dysfunction have recently been illuminated, the underlying molecular processes remain poorly understood. Herein, we evaluate the predictive capacity of the mitochondrial redox environment on sensorimotor brain-behavior dynamics in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art approaches, including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance spectroscopy to measure superoxide levels, antioxidant activity assays and dynamic magnetoencephalographic imaging to quantify sensorimotor oscillatory dynamics. We observed differential modulation of sensorimotor brain-behavior relationships by superoxide and hydrogen peroxide-sensitive features of the redox environment in PLWH, while only superoxide-sensitive features were related to optimal oscillatory response profiles and better motor performance in controls. Moreover, these divergent pathways may be attributable to immediate, separable mechanisms of action within the redox environment seen in PLWH, as evidenced by mediation analyses. These findings suggest that mitochondrial redox parameters are important modulators of healthy and pathological oscillations in motor systems and behavior, serving as potential targets for remedying HIV-related cognitive-motor dysfunction in the future.

Original languageEnglish (US)
Pages (from-to)265-275
Number of pages11
JournalBrain, Behavior, and Immunity
Volume107
DOIs
StatePublished - Jan 2023

Keywords

  • EPR spectroscopy
  • Hydrogen peroxide
  • Magnetoencephalography
  • Motor cortex
  • Neural oscillations
  • Seahorse analyzer
  • Superoxide

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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