Macroautophagic process was differentially modulated by long-term moderate exercise in rat brain and peripheral...

Area of Science:

• Cellular Biology
• Neuroscience
• Exercise Physiology

Background:

• Autophagy is a cellular degradation process crucial for maintaining homeostasis, particularly under stress.
• Regular exercise offers neuroprotective benefits, but the underlying cellular mechanisms, especially regarding autophagy modulation by long-term moderate exercise, remain unclear.
• Previous studies indicate exercise can induce autophagy in both brain and peripheral tissues, but long-term effects require further investigation.

Purpose of the Study:

• To investigate the impact of long-term moderate treadmill training on the macroautophagy process.
• To assess exercise-induced changes in autophagy markers in specific brain regions (hippocampus, cerebral cortex) and peripheral tissues (skeletal muscle, liver, heart) of adult rats.

Main Methods:

• Adult rats underwent 36 weeks of moderate treadmill training.
• Key autophagy-related proteins (mTOR, Beclin 1, p62, LC3B-II/LC3B-I ratio, LAMP1) and ubiquitinated proteins were measured in the cerebral cortex, hippocampus, skeletal muscle, liver, and heart.
• Western blotting and other biochemical assays were employed to quantify protein levels and activation states.

Main Results:

• Long-term moderate exercise led to mTOR inactivation and increased autophagy flux (higher LC3-II/LC3-I ratio, lower p62) in the rat cerebral cortex.
• Enhanced lysosomal activity (increased LAMP1) and reduced ubiquitinated proteins were observed in the cortex of exercised rats.
• No significant changes in autophagy markers were detected in the hippocampus, skeletal muscle, or cardiac muscle; the liver showed increased mTOR phosphorylation and p62 levels.

Conclusions:

• Long-term moderate exercise specifically induces macroautophagy in the cerebral cortex, suggesting a targeted neuroprotective mechanism.
• The observed changes in the cortex, including reduced mTOR signaling and enhanced degradation pathways, may contribute to the beneficial effects of exercise on brain health.
• Exercise-induced alterations in the liver may relate to beneficial metabolic adaptations, distinct from the cortical autophagic response.