Effect of environmental enrichment on brain-derived neurotrophic factor activity for mitigating behavioral manifestations in an autism spectrum disorder model: A systematic review

Abstract

• Environmental enrichment (EE) increases BDNF levels in ASD animal models. • BDNF response to EE differs by sex, brain region, and ASD animal model. • Prolonged EE exposure early in life maximizes BDNF increase. • Communal nesting during EE amplifies its impact on BDNF levels. • Standardized EE protocols are needed to improve reproducibility in ASD studies. Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that has been associated with altered Brain-Derived Neurotrophic Factor (BDNF) levels. Environmental Enrichment (EE), a non-pharmacological intervention, has been proposed to modulate BDNF levels and improve ASD-related behaviors. This systematic review seeks to evaluate the current literature on the impact of EE on BDNF levels and its potential to alleviate ASD-related behaviors in rodent models. This systematic search was performed in PubMed, Web of Science, and Scopus in April 2024. Primary inclusion criteria encompassed animal intervention studies examining the effects of EE on BDNF levels in ASD models. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality assessment of studies was conducted using the S Y stematic Review Centre for Laboratory a nimal Experimentation (SYRCLE) Risk of Bias tool. The data were extracted and synthesized on molecular BDNF levels and ASD-related behavioral outcomes. Out of 1,588 unique records, seven articles met the inclusion criteria. These studies have utilized various approaches to model ASD and different EE protocols. Six of the seven studies reported a positive effect of EE on BDNF levels and behavioral outcomes. However, the variability in findings underscores the influence of factors such as the specific EE protocol, ASD modulation approaches, sex, and possibly brain region examined, in modulating the effects of EE. The high heterogeneity complicated the comparison between the studies and the conduct of a meta-analysis. The systematic review protocol was registered in PROSPERO under registration number CRD42024517384.