Comparative Study of the Mnemotropic Activity of Dimeric Dipeptide Mimetics of Individual NGF and BDNF Loops Using a New-Object Recognition Test in Rats

It is well known that the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are involved in learning and memory. Specialists of Zakusov Research Institute of Pharmacology designed and synthesized dimeric dipeptide mimetics of the 1 st (GK-6) and 4 th (GK-2) NGF loops and the 1 st (GSB-214), 2 nd (GTS-201), and 4 th (GSB-106) BDNF loops that in vitro activated TrkA or TrkB receptors, respectively. Differences in the activation of PI3K/AKT, MAPK/ERK, and PLC-γ1 were recorded during incubation in HT-22 cell culture for 5 – 180 min. This work was aimed to study the mnemotropic activity of the original NGF and BDNF mimetics in the new-object recognition test in rats. The dipeptides were administered once intraperitoneally. It was found that GK-2 (0.5 and 1.0 mg/kg) and GSB-214 (0.1 and 1.0 mg/kg), activating PI3K/AKT and PLC-γ1 signaling pathways without affecting MAPK/ERK, statistically significantly improved long-term memory. Dipeptides GK-2 and GSB-214 seem promising for further development as drugs for correcting memory impairments.