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    Can Environmental Enrichment Mitigate Cell Apoptosis in the Central Nervous System Under Adverse Health Conditions? A Systematic Review
    (Wiley, 2026) de Sousa Fernandes, Matheus Santos; Ferreira, Diorginis Jose Soares; Yagin, Fatma Hilal; Badicu, Georgian; Santos, Gabriela Carvalho Jurema; Guedes, Maria Carolina Santos; Ardigo, Luca Paolo
    To summarize the available evidence in the literature regarding the effects of exposure to an enriched environment (EE) on the modulation of apoptotic markers in central tissue of rodents under unfavorable conditions. Searches were conducted in three databases: PubMed/Medline (70 articles), Scopus (65 articles), and EMBASE (128 articles), all of which were subjected to eligibility criteria. Of the 263 articles found, 95 duplicates were removed. After evaluating the title and abstract, 147 studies were excluded, leaving 21 articles, 16 of which were included in this systematic review. EE was implemented using various inanimate objects. The disruptive event/condition included social isolation, cerebral ischemia, stroke, postpartum depression, accelerated aging, ischemia/reperfusion, high altitude, Alzheimer's disease, hypobaric hypoxia, infrasound exposure, sepsis, and exposure to sevoflurane. Regarding the expression of apoptotic markers, after EE exposure, there was a reduction in the expression of p-IKK beta/IKK beta and p-P65/P65 in the hippocampus, a reduction in Bax, as well as cleaved Caspase-3, Cytochrome C, a reduction in the Bax/Bcl-2 ratio, and p53. As for anti-apoptotic markers, increased expression of Bcl-2 was observed following EE exposure. This systematic review concludes that the benefits of EE can reduce apoptosis through the modulation of both pro-apoptotic and anti-apoptotic genes. In this regard, EE has been shown to be an important neuroprotective tool in various adverse conditions, mitigating cognitive deficits by reducing apoptosis related to cellular stress.