Evidence Hub

Can Environmental Enrichment Mitigate Cell Apoptosis in the Central Nervous System Under Adverse Health Conditions? A Systematic Review

M. S. de Sousa Fernandes, D. J. Ferreira, F. Yağın, G. Badicu, G. Santos, Maria Carolina Santos Guedes, F. Souto, L. Ardigò

Clinical and Translational Science, 2026

Abstract

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‐IKKβ/IKKβ 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…

How strong is the evidence?

Evidence Hub reads this as a systematic review. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

Read the paper

Related studies

Go deeper in Evidence Hub

Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.

Open this study Sign up free