[Behavioral and molecular effects of endogenic kynurenines deficit in the honeybee (Apis mellifera L.)].

The importance of tryptophan endogenous metabolites kynurenines in the long-term memory and functioning of the signal cascade GluR - LIMK1 - F-actin, mediating the long-term memory trace storage, was demonstrated. The deficit of kynurenines induced by allopurinol (tryptophanoxygenase inhibitor) suppressed the long-term memory, decreased the LIMK1 expression, and paradoxically increased the F-actin content in the honeybee brain. These data agree with the earlier findings in drosophila mutant vermilion (the mutation of tryptophanoxygenase gene).

Electrophysiological characteristics of a population of mushroom body neurons in Apis Mellifera honeybees in kynurenine deficiency.

Electrophysiological methods were used to study the neurophysiological characteristics of mushroom body neurons in snow (laranja) mutant and wild-type bees. The snow (laranja) mutation, which produces a sharp reduction in the activity of the enzyme tryptophan oxygenase, thus creating a deficiency of all kynurenines in the body, modifies the bioelectrical properties of mushroom body neurons. The parameters most dependent on the snow (laranja) mutation and, thus, the level of endogenous kynurenines, were the duration of action potential afterdepolarization recorded from neurons in the calyx and the amplitude of the postsynaptic potential of neurons in the calyx evoked by focal stimulation of the antennal lobes. There was also a tendency to an increase in the spontaneous spike frequency. These data lead to the conclusion that the effect of the mutation is recessive in nature and appears only in homozygotes (bearing two mutant alleles).

Characteristics of neuron activity in the honey bee (Apis mellifera L.) in conditions of kynurenine deficiency.

Neuron activity was studied electrophysiologically in the antennal lobes, mushroom bodies, and cervical connective during ontogenesis (days 1, 3, 7, and 25) in snow(laranija) mutant bees, which suffer kynurenine deficiency, and in wild-type bees. Neuron activity recorded from the cervical connective was found to show the greatest dependence on kynurenine content. Mutation in the structural gene for tryptophan oxygenase, the first and key enzyme in the kynurenine pathway for tryptophan metabolism (KPTM) and which leads to kynurenine deficiency, decreased the frequency of neuron spike activity recorded from the cervical connective. This would appear to be associated with a possible deficiency of glutamic acid; it was independent of the deficiency of kynurenic acid and kynurenine, a point subject to further studies. Clear manifestation of the effect of the mutation requires the presence of two mutant alleles in the bee genome (homozygosity). The effect of the mutation, to inhibit neuron activity in the cerebral ganglion, corresponds to the effect seen previously at the behavioral level. Less clear effects were obtained from recordings of neuron activity from the antennal lobes and mushroom bodies. This may be associated with the complexity of the spectrum of biochemical lesions in different parts of the brain resulting from the mutation.

[Electrophysiological characteristics of a population of mushroom body neurons in Apis mellifera L. honey bee under conditions of kynurenines deficit].

Neurophysiological characteristics of mushroom body neurons were examined by electrophysiological methods in mutants snow(laranja) and wild-type honey bees. Mutation snow(laranja) causes a drastic decrease in the activity of enzyme tryptophane oxygenase that results in deficiency of all kynurenines. It also modifies bioelectrical properties of neurons in the mushroom bodies. The duration of afterdepolarization in spikes recorded from calyx neurons and the amplitude of postsynaptic potentials in these neurons evoked by focal stimulation of antennal lobes were shown to be most dependent on the mutation and, consequently, on the content of endogenous kynurenines. A tendency to an increase in the frequency of spontaneous spikes was also observed. The effect of the mutation on neurophysiological characteristics under study was recessive, i.e. it was observed only in homozygous individuals.

Central non-NMDA receptors of a honey bee with hereditary kynurenine deficiency.

Pharmacological characteristics of non-NMDA receptors involved in associative learning were studied in wild honey bees (normal) and carriers of snow laranja mutation (kynurenine deficiency) by pharmacological analysis and behavioral criteria. The effects of systemic injections of non-NMDA receptor agonists (AMPA, kainic, quisqualic, and domoic acids), AMPA receptor antagonist (NS257-HCl), and AMPA receptor modulator (cyclothiaside) on retention of conditioned reflexes in short-term memory (1 min after the end of learning) were studied. The pharmacological characteristics of non-NMDA receptors were changed in snow laranja mutants with kynurenine deficiency.

Early kynurenergic impairment in Huntington's disease and in a transgenic animal model.

Several neuroactive metabolites of the kynurenine pathway of tryptophan degradation have been speculatively linked to the pathophysiology of Huntington's Disease (HD). Here we demonstrate that the levels of two of these metabolites, the free radical generator 3-hydroxykynurenine (3HK) and the neuroprotectant kynurenate (KYNA), are increased in the neostriatum of stage 1 HD patients and in the brain of mice transgenic for full-length mutant huntingtin. In both cases, the elevation in 3HK was far more pronounced, resulting in significant increases in the 3HK/KYNA ratios. These data suggest that abnormal kynurenine pathway metabolism may play a role during the early phases of the neurodegenerative process in HD.

[NMDA-Receptors in the central nervous system of the honey bee with kynurenine deficiency]. / NMDA-Retseptory tsentral'noi nervnoi sistemy medonosnoi pchely v usloviiakh defitsita kinureninov.

Effects of some drugs on the short-term memory were tested. In kynurenine deficit, mutant snow laranja manifested the same pharmacological profile and 10 to 100-fold enhancement of sensitivity of the NMDA receptors' different sites. The data obtained suggest that the gene controlling the key enzyme activity of the kynurenine pathway of tryptophan metabolism is involved in regulation of the CNS NMDA receptors' functional condition. The kynurenines may be classified as endogenous modulators of the NMDA receptor sensitivity.

[Plasma kynurenine levels and the dexamethasone test in patients with endogenous anxiety disorders and depression]. / Kinurenin plazmy krovi i deksametazonovyi test u bol'nykh s éndogennoi trevogoi i depressiei.

As many as 30 patients with affective psychoses were examined for the concentration of plasma kynurenine, a neuroactive tryptophan metabolite, and for the parameters of the dexamethasone test. A group of patients suffering from "endogenous anxiety" and endogenous depression were distinguished. In the patients' group with "endogenous anxiety", the concentration of kynurenine at the height psychosis was significantly higher as compared to controls, correlating with the gravity of anxious symptomatology. In the patients' group with endogenous depression, plasma kynurenine was significantly lower than in controls but did not agree with the depression gravity. The dexamethasone test appeared pathological only in the group of patients suffering from endogenous depression and its parameters correlated well with the gravity of depressive symptomatology. In both groups, the study parameters returned to normal after the egress from the morbid condition.