Halogenated (Cl-ion) songorine is a new original agonist of fibroblast growth factor receptors of neuronal-committed progenitors possessing neuroregenerative effect after cerebral ischemia and hypoxia in experimental animals

Abstract

Alkaloids, which possess a stimulating effect on the functions of progenitors of various classes, were identified. The aim of this study was to identify mechanisms underlying development neuroregenerative effects of modified (halogenated (Cl-ion)) alkaloid songorine (mSON). To reveal the participation of neuronal-committed progenitors (clonogenic PSA-NCAM + cells) subventricular area of cerebral hemispheres (SVZ) in the realization of pharmacological action of this substance and to study the mechanisms of stimulating their functions under the influence of mSON. mSON was received by halogenation (Cl-) of alkaloid and administered to the experimental animals after modeling cerebral ischemia (rats) and posthypoxic encephalopathy (mice). Therapeutic effects of mSON were assessed with the help of functional and morphological methods. To study the effect of mSON on clonogenic PSA-NCAM + cells, the role of receptors to the growth factor of fibroblasts (FGFR) and intracellular signaling molecules of neuronal-committed progenitors in their implementation. Normalization of behavior and reflexive activity on the background of significant correction of morphological pattern malfunctions in the brain of experimental animals during mSON administration after modeling of brain pathology was revealed. The increase in the number of clonogenic PSA-NCAM + cells in SVZ was determined. It was shown a direct stimulating effect of mSON on neuronal-committed progenitors, which was abolished by the addition of anti-FGFR. Significant differences in intracellular signaling in clonogenic PSA-NCAM + cells while stimulating their functions with mSON and growth factor of fibroblasts were determined. These results suggested that mSON is a new original agonist of neuronal-committed progenitors FGFR. mSON is a promising one for the development of a safe and highly effective drug for neurological practice.