Prior Exercise Attenuates LPS-Induced Neuroinflammation, Dopaminergic Dysfunction, and Fatigue-like Behavior in Mice

Area of Science:

• Neuroscience
• Exercise Physiology
• Immunology

Background:

• Neuroinflammation is a key factor in central fatigue, affecting motivation and brain signaling.
• Systemic inflammation can disrupt dopaminergic pathways crucial for cognitive and motor functions.

Purpose of the Study:

• To determine if prior voluntary exercise can mitigate behavioral, physiological, and neurochemical changes caused by systemic inflammation.
• To investigate the impact of exercise on neuroinflammation and dopaminergic metabolism during LPS-induced inflammation.

Main Methods:

• Adult male mice were divided into sedentary and exercise groups (6 weeks of wheel running).
• Systemic inflammation was induced using lipopolysaccharide (LPS); controls received saline.
• Behavioral tests, maximal oxygen consumption (V̇O2max), grip strength, prefrontal cortex cytokine levels (IL-1β, IL-6), and dopaminergic metabolism were assessed.

Main Results:

• LPS exposure increased IL-1β and IL-6 levels, disrupted dopamine metabolism, and impaired behavior and physical performance.
• Prior exercise attenuated IL-6 increases, preserved dopaminergic markers, and improved behavioral and metabolic outcomes.
• Protection was incomplete, as IL-1β levels remained elevated.

Conclusions:

• Systemic inflammation leads to central nervous system dysfunction, characterized by neuroinflammation and altered dopaminergic signaling.
• Pre-existing physical activity offers partial protection against inflammation-induced central fatigue.
• Exercise may be a viable preventive approach against fatigue associated with inflammatory conditions.