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    Is environmental enrichment effective in modulating autophagy markers in the brain exposed to adverse conditions? A systematic review
    (Frontiers Media Sa, 2025) Silva, Clarice Beatriz Goncalves; de Sousa Fernandes, Matheus Santos; Cerqueira, Debora Dantas Nucci; Santos, Gabriela Carvalho Jurema; Yagin, Fatma Hilal; Aygun, Yalin; Badicu, Georgian
    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.
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    Three weeks of environmental enrichment enhance hepatic-muscular oxidative balance and decrease interleukin-6 levels in juvenile female C57BL/6 mice
    (Frontiers Media Sa, 2025) Fidelis, Debora Eduarda da Silva; Fernandes, Matheus Santos de Sousa; Ramos, Tiago Lacerda; Silva, Clarice Beatriz Goncalves; Perreira, Allifer Rosendo; Nobrega, Cassia Giselle de Olivera; de Souza, Valdenia Maria Oliveira
    Introduction The Environmental Enrichment (EE) promotes systemic responses through social, cognitive, sensory, and physical stimuli. However, its effects on hepatic and muscle oxidative balance, as well as on serum inflammation markers, remain unclear. Therefore, this study aimed to evaluate whether three weeks of EE could modulate hepatic and muscular oxidative balance and the inflammatory response in female C57BL/6 mice.Methods The animals were divided into two groups: EE (n = 13) and Standard Environmental (SE, n = 11) from postnatal day 35 to 60. The EE setting included inanimate objects such as tunnels, ladders, and toys made of both wood and plastic. After three weeks, the mice were euthanized for the withdrawal of the liver, extensor digitorum longus (EDL), soleus, and blood samples.Results and discussion EE significantly reduced body weight and malondialdehyde levels in the liver, soleus, and EDL muscles. Additionally, carbonyl levels decreased in the liver and soleus. Acute EE exposure enhanced enzymatic antioxidant activity (SOD, CAT, and GST) across all tissues, except for catalase activity in the EDL, which showed no significant difference between groups. Non-enzymatic defenses were improved, with reduced oxidized glutathione (GSSG) levels in the liver and soleus. Furthermore, EE increased the REDOX status in the liver and EDL. Sulfhydryl levels increased only in the liver. Finally, serum cytokine analysis revealed a significant reduction only in IL-6 levels. These findings suggest that three weeks of EE can modulate hepatic and muscular oxidative balance, as well as serum IL-6 levels, in juvenile female mice.