AUTHOR=Silva Clarice Beatriz Gonçalves , de Sousa Fernandes Matheus Santos , Cerqueira Debora Dantas Nucci , Santos Gabriela Carvalho Jurema , Yagin Fatma Hilal , Aygun Yalin , Badicu Georgian , Evangelista Fabiana S. , Prieto-González Pablo , Souto Fabrício Oliveira , Dutta Ashit Kumar , Al-Mhanna Sameer Badri , Tabnjh Abedelmalek Kalefh 

TITLE=Is environmental enrichment effective in modulating autophagy markers in the brain exposed to adverse conditions? A systematic review

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2025.1624500

DOI=10.3389/fncel.2025.1624500

ISSN=1662-5102

ABSTRACT=Autophagy is a key regulator of cellular homeostasis and neuronal survival, particularly under adverse physiological conditions. Environmental enrichment (EE), a non-pharmacological intervention providing enhanced sensory, cognitive, and motor stimulation, may modulate autophagic processes in the brain. This systematic review aimed to synthesize preclinical findings on the effects of EE on autophagy markers in rodent models subjected to diverse adverse conditions. A literature search across PubMed, Scopus, ScienceDirect, and embase yielded eight eligible studies meeting inclusion criteria. EE was found to be generally associated with upregulation of key autophagic markers such as Beclin-1, LC3-II/LC3-I ratio, cathepsins, p62, p-TFEB, and LAMP-1 across brain regions including the cortex, hippocampus, and penumbral area. However, reductions in some markers were also observed, indicating that the modulatory effects of EE are context-dependent and may vary with disease model, brain region, or EE protocol duration. These findings suggest that EE holds promise as an adjunctive strategy to modulate autophagy and mitigate neurodegeneration, though heterogeneity in study design and outcomes warrants caution during interpretation. Further mechanistic and sex-specific studies are needed to clarify the therapeutic relevance of EE-induced autophagic modulation.