Related Experiment Video
Updated: Feb 23, 2026
Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue
Published on: August 15, 2012
IRF2BP2-deficient microglia block the anxiolytic effect of enhanced postnatal care
Aswin Hari1,2, Shelly A Cruz1, Zhaohong Qin1
1Ottawa Hospital Research Institute, Ottawa, Canada.
Abstract:
Enhanced postnatal care (EPC) increases resilience to adversity in adulthood. Since microglia participate in shaping neural circuits, we asked how ablation of an inflammation-suppressing factor IRF2BP2 (Interferon Regulatory Factor 2 Binding Protein 2) in microglia would affect the responses to EPC. Mice lacking IRF2BP2 in microglia (KO) and littermate controls (WT) were subjected to EPC during the first 3 weeks after birth. EPC reduced anxiety in WT but not KO mice. This was associated with reduced inflammatory cytokine expression in the hypothalamus. Whole genome RNAseq profiling of the hypothalamus identified 101 genes whose expression was altered by EPC: 95 in WT, 11 in KO, with 5 in common that changed in opposite directions. Proteoglycan 4 (Prg4), prostaglandin D2 synthase (Ptgds) and extracellular matrix protease inhibitor Itih2 were suppressed by EPC in WT but elevated in KO mice. On the other hand, the glutamate transporter VGLUT1 (Slc17a7) was increased by EPC in WT but not KO mice. Prostaglandin D2 (PGD2) is known to enhance microglial inflammation and promote Gfap expression. ELISA confirmed reduced PGD2 in the hypothalamus of WT mice after EPC, associated with reduced Gfap expression. Our study suggests that the anxiety-reducing effect of EPC operates by suppressing microglial inflammation, likely by reducing neuronal prostaglandin D2 production.
Insights
Enhanced postnatal care (EPC) reduces anxiety by suppressing microglial inflammation. This effect is dependent on the IRF2BP2 protein in microglia, highlighting its role in stress resilience.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Enhanced postnatal care (EPC) promotes resilience to adult adversity.
- Microglia play a crucial role in neural circuit development and plasticity.
- IRF2BP2 is an inflammation-suppressing factor expressed in microglia.
Purpose of the Study:
- To investigate the role of microglial IRF2BP2 in mediating the effects of EPC on anxiety.
- To explore the molecular mechanisms by which EPC influences microglial function and neural circuits.
Main Methods:
- Utilized a mouse model with microglia-specific knockout of IRF2BP2 (KO) and wild-type (WT) littermates.
- Subjected mice to EPC during the early postnatal period (first 3 weeks).
- Assessed anxiety-like behaviors, hypothalamic gene expression (whole genome RNAseq), and prostaglandin D2 (PGD2) levels.
Main Results:
- EPC reduced anxiety in WT mice but not in KO mice, indicating IRF2BP2's necessity.
- EPC suppressed inflammatory cytokine expression in the hypothalamus of WT mice.
- Gene expression profiling revealed distinct molecular changes in response to EPC between WT and KO mice, including altered expression of genes related to extracellular matrix and glutamate transport.
- Reduced hypothalamic PGD2 levels and GFAP expression were observed in WT mice post-EPC.
Conclusions:
- The anxiety-reducing effects of EPC are mediated by the suppression of microglial inflammation, dependent on IRF2BP2.
- Neuronal prostaglandin D2 production may be a key target through which EPC modulates microglial activity and promotes stress resilience.
