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.