Shymanskyy I. Molecular mechanisms of neurotropic action of vitamin PP and its biologically active derivatives

Object: Modulation of synaptic activity under different functional states of central nervous system. Aim: to investigate the molecular mechanisms of NAD involvement in modulation of synaptic transmission via NAD-binding protein as well as neurotropic action of vitamin РР and it's biologically active derivatives in type 1 diabetes. Methods: radioligand assay, enzymological analysis, methods of preparative biochemistry, biokinetic and statistic analysis. It was found that NAD-induced serotonin release from synaptosomes involves the activation of protein kinase C and/or A pathways which probably links inhibition of Na,K-ATPase activity and depolarization of synaptic membranes. The data obtained provide evidence that diabetes leads to physiologically drastic failure in realization of serotonin-mediated effects in central nervous system resulting from augmented NAD binding to synaptic membranes. The mechanism of positive nicotinamide and nicotinoyl-GABA neurotropic action was shown to be associated with thedecrease in diabetes-related elevation of serotonin release from isolated synaptic endings that was accompanied by normalization of NAD reception, slowing down the oxidative stress and inhibition of protein mono- and poly-ADP-ribosylation. The study confirms the complex pattern of vitamin PP neuroprotective action that can be useful in the treatment of diabetic neuropathy.