Can the effects of environmental enrichment modulate BDNF expression in hippocampal plasticity? A systematic review of animal studies

Background and aim: Environmental enrichment (EE) can be related to changes in the expression of brain‐derived neurotrophic factor (BDNF) in the hippocampus of adult rodents. Exposure to EE may also induce neurogenesis in the dentate gyrus (DG). The aim of this systematic review was to analyze the current literature on the correlation between neurogenesis and BDNF expression in the hippocampal DG region resulting from exposure to EE, which is associated with changes in memory, in rodents. Methods: Bibliographic searches of the Medline/PubMed and ScienceDirect databases were carried out, and 334 studies were found. A predefined protocol was used and registered on PROSPERO, and 32 studies were included for qualitative synthesis. The PRISMA was used to report this systematic review. Results: Most of the included studies showed that there is little evidence in the literature demonstrating that memory changes resulting from EE are dependent on BDNF expression and that there is an induction of neurogenesis in the hippocampal DG. However, the observed increase in molecular expression levels and cell proliferation is dependent on the age, the timing and duration of exposure to EE. Regarding the methodological quality of the studies, the majority presented a risk of bias due to the high variability in the age of the animals. Conclusion: There are few studies in the literature that correlate the molecular and cellular mechanisms involved in neurogenesis in the hippocampal DG with BDNF expression in this region in rodents exposed to EE; however, there are other factors that can modulate this neurogenesis. A schematic representation of the influences of environmental enrichment on the mechanism of hippocampal neurogenesis in adult rats and a photomicrograph of a coronal section of the hippocampus of a 3‐month‐old control rat stained with eosin and hematoxylin and showing the DG (dentate gyrus). BDNF = brain‐derived neurotrophic factor, Negr1 = neuronal growth regulator 1, VEGF = angiogenic factor, NGF = nerve growth factor.