Soybean-Derived Glycine–Arginine Dipeptide Administration Promotes Neurotrophic Factor Expression in the Mouse Brain

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in cognitive abilities, including memory and learning. We demonstrated that soybean protein hydrolysate (SPH) diet suppresses age-related cognitive decline via the upregulation of BDNF in a mouse model of senescence. Our purpose was to identify novel bioactive peptides in SPH, which enhance BDNF expression. We treated mouse primary astrocytes with SPH as well as with its positively charged chromatographic fraction. Significant increases in the expression of BDNF were observed in the treatment with positively charged fraction of SPH. Among the synthesized peptides, the dipeptide glycine–arginine (GR) increased BDNF expression in vitro, and LC-TOF-MS analysis showed the presence of GR in the SPH. Furthermore, its administration in vivo increased the expression of BDNF in the cerebral cortex and the number of neurons in hippocampus and cerebral cortex. These data indicate that GR might promote neurogenesis by upregulating BDNF levels.