Enriched Environment Enhances Motor Function in Mice With Cerebral Infarction by Promoting mTOR-Dependent Autophagy...

Area of Science:

• Neuroscience
• Cellular Biology
• Regenerative Medicine

Background:

• Environmental enrichment (EE) is known to improve motor function post-stroke.
• The precise molecular mechanisms by which EE influences cerebellar plasticity, particularly in the dentate nucleus (DN), are not fully understood.

Purpose of the Study:

• To investigate how EE coordinates autophagy, mitochondrial homeostasis, and synaptic remodeling in the contralateral DN after stroke.
• To elucidate the role of the mTOR pathway and neuroinflammation in EE-mediated functional recovery.

Main Methods:

• Utilized a permanent middle cerebral artery occlusion (pMCAO) mouse model.
• Assessed motor function using rotarod and ladder rung tests.
• Analyzed ultrastructural changes, autophagy markers (LC3B, p62), mitochondrial integrity, neuroinflammation (cytokines TNF-α, IL-1β, IL-6), and mTOR signaling via Western blotting and ELISA.

Main Results:

• EE significantly improved motor coordination and reduced neuronal degeneration.
• Enhanced autophagic activity (increased LC3B, decreased p62) and preserved mitochondrial integrity were observed.
• EE attenuated neuroinflammation and suppressed pro-inflammatory cytokines, linked to mTOR pathway inhibition, and promoted synaptic remodeling.

Conclusions:

• EE promotes post-stroke motor recovery by activating a repair loop in the dentate nucleus.
• Autophagy-mediated mitochondrial clearance and reduced neuroinflammation create a favorable environment for synaptic remodeling.
• The dentate nucleus is a key hub for EE's therapeutic effects, suggesting combined strategies targeting autophagy-mitochondrial pathways for rehabilitation.