CHANGES IN LIPID COMPOSITION AND FUNCTIONAL ACTIVITY OF DAMAGED SOMATIC NERVES UNDER THE ACTION OF FISETIN AND INSULIN-LIKE GROWTH FACTOR-1

Abstract

Annotation. The lipid composition and phospholipase activity of damaged somatic nerves against the background of fisetin and insulin-like growth factor-1 (IGF-1) action were investigated. It was shown that nerve transection is accompanied by an increase in the content of phosphatidylinositol (PI) and free fatty acids (FFA) and a decrease in the level of diacylglycerol (DAG) in both proximal and distal sections of the nerve conductor, apparently as a result of inactivation of phosphoinositide-specific phospholipase C. Against the background of intramuscular administration of IGF-1 at a concentration of 100 ng/kg, intensification of phosphoinositide metabolism, accumulation of DAG and reduction of FFA levels were observed. When fisetin was administered, insignificant changes in the content of FI and DAG were observed throughout the entire period of the experiment in both proximal and distal sections of the nerve conduit. The methods of Raman spectroscopy and action potential registration revealed the restoration of the physicochemical state of the lipid bilayer and functional activity in the proximal segment of somatic nerves when these drugs were used; nevertheless, the mechanism of their action remains different. We believe that IGF-1 administration intensifies the metabolism of phosphoinositide cycle components, indicating a phospholipase C - mediated mechanism of IGF-1 action in injured somatic nerves, which further leads to the formation of components of the phosphatidylinositol-3-kinase signalling pathway involved in the stimulation of expression of various transcription factors necessary for axonal regeneration and restoration of the functioning of injured nerve conductors. In contrast to IGF-1, the absence of intensification of phosphoinositide metabolism and increased synthesis of protein fraction under fisetin action indicates acceleration of regeneration processes in the injured nerve conductor, most likely caused by activation of mitogen-activated protein kinase signalling pathway, which is accompanied by expression of genes associated with remyelination and restoration of physicochemical state of nerve fibre membrane due to protein synthesis.