The effects of estrogens on learning in rats with chronic brain cholinergic deficiency in a Morris water test. Identification of the "passive swimming" component.

Chronic decreases in brain cholinergic functions due to intraventricular administration of the neurotoxin AF64A were accompanied by increases in the latent period of locating an invisible platform during training of rats in a Morris water test, as compared with control sham-operated animals. Recordings of the animals' movement trajectories using a video camera along with an original computer program (Behavioral Vision) showed that administration of 17beta-estradiol and its synthetic analog J-861 (0.2 mg/kg p.o. daily for seven days before and 10 days after single intraventricular injections of AF64A) improved learning. The directivity of platform search trajectories was assessed quantitatively using a new parameter--trajectory straightness. Introduction of the "passive swimming" parameter allowed periods of immobility in water to be identified within the total latent period in animals after administration of AF64A; 17beta-estradiol but not J-861 "eliminated" these periods. The new parameters (especially trajectory straightness) allowed the ability to learn to be discriminated from decreases in mobility, including mobility losses due to study agents, in the Morris water test.

[Effects of estrogens on learning of rats with chronic brain cholinergic deficit in Morris water maze]. / Vliianie éstrogenov na obuchenie krys s khronicheskim kholinergicheskim defitsitov v mozge v vodnom teste Morrisa. Vydelenie komponenta "passivnogo plavaniia".

A chronic deprivation of brain cholinergic functions in rats caused by intracerebroventricular injection of neurotoxin AF64A increases the escape latency in Morris water maze test as compared to control sham-operated animals. Measurements and analysis of rat movement tracks using an original computerized "Behavioral Vision" system revealed the ability of 17 beta-Estradiol and its synthetic isomer J-861 (both administered daily in per os dose 0.2 mg/kg during 7 days before and 10 days after a single intracerebroventricular injection of AF64A) to improve learning of the animals. Directivity of search trajectories was estimated by a novel index of track straightness. The introduction of an index of "passive swimming" made it possible to reveal episodes of immobility in water-maze behavior of AF64A-injected animals. Unlike J-861, 17 beta-Estradiol almost completely eliminated these episodes. The newly developed indices (especially straightness) seem to be very useful in differentiating learning ability of rats from a decrease in their mobility in the Morris water-maze test, in particular, in case of the estrogens under study.

Comparison of the effect of NT-0409 and antidementia drugs on learning and memory in rats with chronic cerebral cholinergic deficiency.

Systemic oral administration of NT-0409, a new synthetic agonist of AMPA subtype glutamate receptor, to rats with chronic partial AF64A-induced deprivation of cholinergic functions improved their learning in a Morris water maze. NT-0409 is close to memantine by the effect on learning and, in contrast to cholinomimetic arisept, ensures longer retention of the developed habit.

Versatile computerized system for tracking and analysis of water maze tests.

A crucial step in the estimation of properties of compounds in behavioral experiments is the quantification and description of the different effects observed. The goal of the present work was the automation of the Morris water maze test, one of the most popular behavioral methods for the study of animal memory. An original system was developed that provides fast and accurate tracking of animals, storage of the results in the database and video archive and a means of analyzing the results. This computerized version of the Morris water maze test permits the quantification of such vague characteristics of cognitive function as the "directionality" of search of the hidden platform after a standard training series. The suggested parameters made it possible to discriminate cognitive properties of the novel compounds from other behavioral effects affecting escape latency. The effectiveness of this system was demonstrated in two experiments with neurochemically lesioned and drug-treated rats.

The learned symmetry concept in revealing quantitative structure-activity relationships with artificial neural networks.

A method to build QSAR models based on substituent constants for congeneric sets of compounds having several topologically equivalent substituent positions was proposed. The approach is based on the application of artificial neural networks (learning to construct nonlinear structure-activity relationships taking into account necessary symmetry properties of training set structures) to a training set expanded by adding the copies of compounds with the same activity values but with permuted assignment of equivalent substituent positions. The better predictive power of these constructed models, as compared with the performances of neural network models for non-expanded sets was demonstrated for the calcium channel blockers of 1,4-dihydropyridine type and for hallucinogenic phenylalkylamines.

Effects of 17 beta-estradiol and its isomer 17 alpha-estradiol on learning in rats with chronic cholinergic deficiency in the brain.

It was shown for the first time that estrogens 17 beta- and 17 alpha-estradiols compensate impaired cognitive functions in rats with partial chronic deprivation of cholinergic functions in the central nervous system induced by intracerebral administration of selective cholinergic neurotoxin AF64A. 17 beta-Estradiol produced strong dose-dependent changes in the weights of hormone-sensitive endocrine glands, while 17 alpha-estradiol did not affect the weight of the gonads and slightly influenced (in high concentration) the weights of the adrenal glands and thymus. The positive effects of exogenous 17 beta- and 17 alpha-estradiols on cognitive functions are due to their antioxidant properties, rather than due to specific action on hormone-sensitive endocrine glands.

[Characteristic features of protoplast formation and regeneration in Fusidium coccineum]. / Osobennosti obrazovaniia protoplastov i ikh regeneratsii u Fusidium coccineum.

The methods for preparation and regeneration of protoplasts were tested with respect to the strains of F. coccineum markedly differing in their capacity for antibiotic production, sporulation and the growth rate. It was found that the substrate used for the culture growth had a significant effect on the cell wall and sensitivity of the mycelium to lytic enzymes. An enzyme from Hellix pomatia and its combination with lysozyme were used for lysing the culture. The cytological investigation of the time course of the culture lysis revealed a stage-by-stage pattern of protoplast formation by means of fragmentation of the hyphal contents till a ball was formed. Two to 4 protoplasts differing in their size and structure were formed within a cell. The pH value and osmotically stabilizing component had some effect on the rate of protoplast formation. Highly productive strains were characterized by formation of protoplasts heterogenous in their size and by decreased frequency of regenerations. The enzyme-free protoplasts preserved their viability and capacity for germination in osmotically stabilizing media for 72-96 hours of storage at 4 degrees C. On solid media the regeneration frequency reached 38 per cent. The regenerated cells formed colonies morphologically similar to those of the intact culture.