Work

Enriched Environment Enhances Motor Function in Mice With Cerebral Infarction by Promoting mTOR ‐Dependent Autophagy in the Contralateral Dentate Nucleus

Year: 2026

Type: article

Abstract: Although environmental enrichment (EE) promotes post-stroke motor recovery, the mechanisms underlying its regulation of cerebellar dentate nucleus (DN) plasticity remain unclear; this study therefore investigated how EE coordinates autophagy, mitochondrial homeostasis, and synaptic remodeling in the contralateral DN to facilitate functional restoration. Using a permanent middle cerebral artery occlusion (pMCAO) mouse model, we combined behavioral tests (rotarod and ladder rung) with electron microscopy, Western blotting (LC3B, p62, mTOR/p-mTOR), and ELISA (TNF-α, IL-1β, IL-6) to assess motor function, ultrastructural changes, autophagy, and neuroinflammation. Results demonstrated that EE significantly improved cerebellar-mediated motor coordination, reduced neuronal degeneration, and preserved mitochondrial integrity, while enhancing autophagic activity via increased LC3B expression and decreased p62 accumulation. Ultrastructural analysis revealed elevated synaptic density and a shift toward mitochondrial rejuvenation, paralleled by attenuated neuroinflammatory responses and suppressed pro-inflammatory cytokine levels, consistent with mTOR pathway inhibition. These findings indicate that EE promotes motor recovery by activating a self-reinforcing repair loop in the DN, wherein autophagy-mediated mitochondrial clearance and neuroinflammation suppression create a permissive microenvironment for synaptic remodeling, thereby establishing the DN as a pivotal hub for EE's therapeutic effects and supporting combinatory strategies targeting autophagy-mitochondrial pathways to optimize rehabilitation.

Source: The Kaohsiung Journal of Medical Sciences

DOI: 10.1002/kjm2.70167

Authors: Chuan‐Jie Wang, Ke‐Wei Yu, Jun‐Fa Wu, Feng Tao

Institutions: Fudan University, Jinshan Hospital of Fudan University, Huashan Hospital

Language: English

Topic: Stroke Rehabilitation and Recovery

Subfield: Rehabilitation

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,200