S2P39. HOW DO VARIOUS COMPONENTS OF THE ENRICHED ENVIRONMENT AFFECT TRANSCRIPTOMIC RESPONSES IN MICROGLIA?
Kinga Szydlowska1, Maciej Florczyk1, Renan Tivanello1, Zuzanna Luczak-Sobotkowska1, Jan Brozek1, Anthony J. Hannan3, Rosa Chiara Paolicelli4, Ali Jawaid2, Bozena Kaminska1
1 Laboratory of Molecular Neurology, Nencki Institute of Experimental Biology PAS, Warsaw, Poland
2 Translational Neuropsychiatry Research Group, Lukasiewicz Research Network - PORT Polish Center of Technology Development, Wroclaw, Poland
3 Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia
4 Department of Biomedical Sciences, University of Lausanne, Switzerland
INTRODUCTION: Environmental enrichment (EE) is an experimental paradigm that combines physical, sensory, and cognitive stimulation and shows beneficial effects in pre-clinical models of neurodegeneration. Microglia are resident myeloid cells of the central nervous system (CNS), which, through bidirectional communication with other brain cells, maintain CNS homeostasis. In previous studies, EE partially reversed the pro-inflammatory effects of aging on microglia and attenuated the inflammatory response of microglia to Aβ oligomers, thereby promoting their cytoprotective and phagocytic phenotypes.
AIM(S): In this study, we investigated the transcriptomic responses of microglia to EE or its individual components.
METHOD(S): Mice (male and female) were subjected to the full EE or EE without physical exercise, EE without cognitive stimulation, EE without social engagement (single housing of mice); naïve mice or mice single housed without EE were used as controls. Microglia from hippocampi were immunosorted as CD11b+ cells by flow cytometry and subjected to RNA sequencing and computational analyses.
RESULTS: Principal component analysis did not show significant transcriptomic differences between groups in females; however, distinct transcriptomic patterns have been detected between various groups in males. We identified the gene signature associated with EE, which was, to a large extent, induced by physical activity. Gene Ontology (GO) analyses revealed various processes induced by specific EE components, distinct from those of a full EE.
CONCLUSIONS: Interestingly, stress caused by solitary housing abrogated EE-induced gene expression in microglia. Our results demonstrate specific microglial responses to a full EE protocol, as well as its components, shedding light on which elements enhance the protective and modulatory role of microglia.
FINANCIAL SUPPORT: tudies were supported by the National Science Center JPND 2022/04/Y/NZ5/00122.