Роль кинуренинов в регуляции поведения и процессов памяти у дрозофилы

Abstract

Metabolites of the kynurenine pathway of tryptophan metabolism (KPTM) or kynurenines, have a number of neuroactive properties. Disturbances of KPTM are observed in various neuropathologies, such as Huntington, Parkinson, and Alzheimer’s diseases, senile dementia, schizophrenia, depressions, etc. Kynurenines are known to impact processes in nervous cells through two mechanisms — modulation of activity of cellular receptors and modulation of oxidation-reduction potential. Kynurenic acid (KYNA) is a nonspecific antagonist of the ionotropic glutamate receptors and an inhibitor of excitotoxicity. 3-hydroxykynurenine (3HOK) inhibits peroxide oxidation of lipids, but in high concentration owing to an oxidizing autodimerization causes hydrogen peroxide hyperproduction that leads to death of nervous cells. It is convenient to investigate molecular mechanisms of kynurenine neuroactivity on simple model objects, such as bee and Drosophila, where mutations of KPTM genes affect the level of kynurenines. There are several reasons why Drosophila mutants make a good choice to study kynurenine neurotropic properties: 1) Insects do not synthesize NAD from 3HOK, hence, no influence of KPTM defects on power metabolism; 2) Insects do not have certain KPTM metabolites, such as quinolinic acid, which potentiates neurotoxic properties of 3HOK; 3) High level of 3HOK as a response to the synthesis of xanthommatin pigment; 4) Simple methodology of genetic, physiological, molecular and biological research. In Drosophila cardinal (cd) mutant, the accumulation of 3HOK causes irregularities in a male courtship song and the development of synaptic pathology in late stages of imago development. Besides, in cd the age-dependent disturbance of medium-term memory in a paradigm of the conditioned courtship suppression is observed. The above allows to consider cd a model of senile dementia in humans. On the contrary, in cinnabar (cn) mutant with the accumulation of KYNA this neuroprotector has a positive impact on memory and sound production. In general, KPTM products have an activating effect on central nervous system and behavioral processes.