Effect of Low Molecular Weight Nerve Growth Factor Mimetic GK-2 on Cognitive Function and Synaptic Transmission in Hippocampal Slices

Abstract

Nerve growth factor (NGF) contributes to the proliferation, differentiation and maintenance of the viability and functioning of peripheral and central neurons. At the Research Zakusov Institute of Pharmacology a dimeric dipeptide mimetic of the NGF loop 4 bis(monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2) was created. GK-2 activates PI3K/AKT and PLC-γ1 signaling cascades, without affecting MAPK/ERK, and appears to have procognitive properties. In the present study, we investigated the mnemotropic effects of GK-2 with a single intraperitoneal dose of 0.1, 0.5 and 5.0 mg/kg in the novel object recognition test in rats. GK-2 at a dose of 0.5 mg/kg statistically significantly improved the long-term memory of animals. In experiments on the rat hippocampal acute slices, we evaluated the effects of GK-2 on synaptic transmission and its plastic properties in the synaptic system Schaffer collaterals − CA1 pyramidal cell.