We previously reported that rat offspring exposed to curcumin (CUR) from fetal stage revealed anxiolytic effects and enhanced fear extinction learning in behavioral tests, and increased synaptic plasticity in the hippocampal neurogenic niche. This study investigated genes to alter methylation status in the neurogenic niche linked to enhanced cognitive functions by CUR. Methyl-Seq and RNA-Seq were conducted in the dentate gyrus (DG) of CUR-exposed rat offspring on day 77 after delivery. Candidate genes were validated by methylation-sensitive high resolution melting method, real-time RT-PCR, and immunohistochemistry. Hypermethylation and downregulation by CUR were confirmed for Pcdh8, Mmp23, Gpr150 and Rprml. Hypomethylation and upregulation by CUR were confirmed for Opn3, Ppm1j and Fam222a. PCDH8-immunoreactive granule cells decreased the number by CUR. Among the genes obtained, Pcdh8, Opn3, and Fam222a were reported to be expressed in the brain. PCDH8 mediates endocytosis of N-cadherin, a synaptic adhesion molecule, suggesting that the reduction of PCDH8+ granule cells by CUR may induce increased synaptic plasticity to strengthen cognitive function. OPN3 is a light-sensitive transmembrane receptor to function in interneurons. Fam222a encodes aggregatin mainly expressed in astrocytes. Obtained results suggest the involvement of different neural cell populations showing altered methylation and expression of their inherent genes in the neurogenic niche in relation to enhanced cognitive functions by CUR.
