Effects of environmental enrichment on the hippocampal microglial profile under neuroinflammatory conditions: A systematic review
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Published on: December 29, 2014
Clarice Beatriz Gonçalves1, Moara Rodrigues Costa2, Alexandre Kanashiro3
1Keizo Asami Institute, Federal University of Pernambuco, Recife, Pernambuco, Brazil; Postgraduate Program in Applied Biology to Health, Federal University of Pernambuco, Recife, Brazil.
Background:
Environmental enrichment (EE) is a non-pharmacological paradigm that promotes neurogenesis and synaptic plasticity. In the central nervous system, EE modulates neuroinflammation by shifting microglial phenotypes between M1-like proinflammatory and M2-like reparative/homeostatic states. The hippocampus, characterized by high plasticity and vulnerability to inflammatory insults, represents a critical target. This systematic review synthesizes evidence on the effects of EE on hippocampal microglial profiles and neuroinflammatory markers in rodent models of neuropathology.
Methods:
Following PRISMA guidelines, a search was conducted in PubMed/MEDLINE, Scopus, and Embase, with no restrictions on publication date or intervention duration. Articles were included whether they described the murine strains used, the duration and setup of the EE protocols, the adverse conditions evaluated, and outcomes related to neuroinflammatory parameters and hippocampus-specific microglial profiles.
Results:
From 468 records, fifteen studies (2013-2024; moderate SYRCLE quality) met the inclusion criteria. EE reduced microglial density (IBA-1) and M1 markers (CD68/iNOS/MHCII/CCR2), alongside suppression of cytokines (IL-1β/IL-6/TNF-α) and pathways (NLRP3/NF-κB p65/IκB-α). M2 markers (Arg1/CD206/TREM2/IL-10) were upregulated, with morphological shifts toward ramified/phagocytic states and functional phenotypes spanning reparative (33%), homeostatic (40%), and phagocytic (13%) profiles across diverse pathologies.
Conclusions:
EE modulates hippocampal microglia toward a neuroprotective phenotype, attenuating inflammation while promoting context-appropriate repair/phagocytosis across different experimental neuropathologies. These findings highlight the translational potential of EE for lifestyle-based interventions targeting neuroinflammatory disorders.
