Popova L. Neuronal and chemical mechanisms of seizure susceptibility level formation in rats

Object of study: processes of intermediate metabolism of tryptophan (by means of kynurenine pathway) and their interrelation with neurotransmitter processes of rats with different seizure susceptibility. Purpose of study: establishment of neuronal and chemical mechanisms of seizure susceptibility level formation and role of kynurenines in these mechanisms. Methods of study: ethologic (neurobehavioral) investigations; spectrophotometric, fluorometric, chemiluminiscent methods; methods of ion-exchange, high performance liquid, gas, thin layer chromatogra-phy; methods of differential centrifugation; method of fluorescent zondes; statistical. Theoretical and practical significance of results: the obtained results are the new scientific data concerning mechanisms of kynurenines participation in formation of seizure susceptibility of brain. Obtained tendencies give the possibility to newly estimate of kynurenines role in functional activity of brain, in formation of seizure susceptibility and to consider the kynurenine pathway as one of elements of maintenance of synaptic plasticity and definite ratio between excitatory and inhibitory processes in brain. The found dependence of kynurenine influence on the neurotransmitter processes and seizure susceptibility of brain at the initial state of the latter is the base for their more differential and directed application in anticonvulsant therapy depending on the initial mechanisms of seizure manifestations of physiological activity. The obtained data are the main scientific basis of explanation of biological action of group of artificial compounds (namely polyethylene glycols). The latter is used to explanation of state standards of contents of the compounds in environmental objects. Novelty of obtained results: The study shows the important role of kynurenines in chain of neuronal and chemical mechanisms of seizure susceptibility formation. The initial activation of kynurenine pathway of tryptophan metabolism was shown to facilitate the formation of high seizure susceptibility by means of changes in GABA and catecholamines systems and in glutamatergic transmission. In the matured rats the influence of kynurenines on the neurotransmitter processes and seizure susceptibility was found to depend on the initial state of seizure susceptibility. The initial activation of kynurenine pathway of tryptophan metabolism was found to be accompanied by enhanced generation of active oxygen species. The increased control of mediator liberation by means of presynaptic excitatory amino acid receptors, the decrease of negative and increase of positive controls of excitatory neurotransmission were found in rats with high seizure susceptibility. The decrease of inhibitory control by dopamine of excitatory action of glutamate was established in hypothalamus of these animals. That facilitates the activation of GABA-ergic transmission in substantia nigra and evidently has determinal meaning in the formation of high seizure susceptibility. The influence of kynurenines on the neurotransmitter levels was shown to depend on the initial level of seizure susceptibility. General appropriateness that was found is the elimination of differences between groups in levels of the most of mediators. It is found that the influence of kynurenines on the GABA levels is provided by changing in activities of GABA metabolism enzymes and glutamatergic transmission and depends on the initial level of seizure susceptibility. The changes in glycine and aspartate levels under the influence of kynurenines are adaptive and are directed to supporting balance between inhibitory and excitatory processes. The influence of kynurenic acid on the seizure susceptibility was shown to depend on the initial level of latter. Introduction degree: the results are used to upground and update the state standards of polyethylene glycol contents in environmental objects (introduction act № 8/213 from 21.03.02; Resolution of Ministry of Public Health of Ukraine № 15 from 12.12.05). According to the methodic techniques used in the study, we obtained a patent for “The means of determination of neuroactive aminoacids binding parameters (№ 33927 А, G01N 33/48), which is subscribed to the register of new introductions of Ukranian Ministry of Public Health № 18-19-2003. Sphere of application: physiology, neurophysiology, biochemistry.