Present study showed that Senegenin treatment reversed the protein levels of NR2B, HGN and the ratio of NR2B/HGN, as well as enhanced learning and memory, which in accordance with the previous research that Senegenin attenuates cognitive impairment by up‐regulating expression of hippocampal NR2B expression in rats.28 While treatment with HGN antisense oligonucleotide inhibited the expression of HGN protein, reversed the ratio of NR2B/HGN and the learning and memory impairment as previous report.18 This evidence concerns the gene GRIN2B and memory impairment.