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Biomedical subjects

Z I Storozheva

Publications and source records attributed to Z I Storozheva.

At least 19 recordsLinked to original sources

Hexapeptides HLDF-6 and PEDF-6 restore memory in rats after chronic intracerebroventricular treatment with beta-amyloid peptide Abeta(25-35).

Effects of homologous peptides HLDF-6 and PEDF-6 on behavior of animals with experimental Alzheimer's disease induced by chronic intracerebroventricular administration of beta-amyloid peptide Abeta(25-35) were studied in the zoosocial recognition test and Morris water maze. Peptides HLDF-6 and PEDF-6 possessed neuroprotective activity and counteracted the toxic effect of Abeta(25-35). Peptides HLDF-6 and PEDF-6 mainly improved long-term memory and working memory, respectively.

Amyloid beta-Peptides↗

Biochemical markers of apoptosis in different parts of the brain during learning.

Caspase-3 activity and the levels of DNA fragments of 200-600 and >4000 b.p. were estimated in the cerebellar vermis, the hippocampus, and the prefrontal cortex of the brains of adult rats four and 24 months after training to extinction of the acoustic startle reaction and conditioned fear. Differently timed changes in the levels of biochemical markers of apoptosis were seen to different extents in these brain areas after training. These changes were characterized by a decrease in caspase-3 activity in the cerebellar vermis and the hippocampus, with decreases in DNA fragmentation in the hippocampus and cerebral cortex and increases in measures of programmed cell death in the hypothalamus. These experimental data support the view that the apoptosis of cells in the mature brain is involved in the mechanisms of learning and memory.

Acoustic Stimulation↗

Different mechanisms of protective and differentiative activities of homological peptides TGENHR and TQVEHR.

Previously we identified a six-membered fragment 354TQVEHR359 of the C-terminal part of the PEDF (Pigment Epithelium-Derived Factor) differentiation factor molecule that shares homology with fragment 41TGENHR46 of the HLDF (Human Leukemia Differentiation Factor) differentiation factor molecule, which is responsible for its differentiation activity. HLDF has been isolated from the culture medium of human promyelocytic leukemia cell line HL-60. Hexapeptides HLDF-6 (TGENHR) and PEDF-6 (TQVEHR) corresponding to these HLDF and PEDF molecule fragments, which were previously shown to induce cell differentiation (Kostanyan et al. (2000) Russian Journal of Bioorganic Chemistry, 26, 505-511), also have neuroprotective properties. Both peptides prevent degeneration of Purkinje cells of rat cerebellar vermis upon chemical hypoxia induced by sodium azide in vivo; this effect is also observed on a behavioral level. Peptide HLDF-6 but not PEDF-6 promotes survival of HL-60 cells upon chemical hypoxia. Peptides HLDF-6 and PEDF-6 affect different second messenger biosynthesis systems in HL-60 cells. HLDF-6 diminishes cyclic AMP level in those cells due to adenylate cyclase inhibition, while PEDF-6 inhibits phosphatidylinositol-specific phospholipase C stimulated by aluminum tetrafluoride anions.

Adenylyl Cyclases↗

Heterochronous involvement of neurotrophic factors in the neurochemical organization of learning and memory processes in adult organisms.

Studies were performed on the involvement of neurotrophic factors in the neurochemical mechanisms of the integrative functions of the brain. The effects of various intrahippocampal doses of antibodies to neurotrophic factors--protein S100 and lectin CSL--were studied on the formation, retention, and reproduction of a habituated acoustic startle response and conditioned fear in adult rats. S100b contents in the hippocampus, hypothalamus, frontal cortex, and cerebellar hemispheres and vermis, and in the basal nuclei were measured in rat brains 0.5, 1, 2, 4, 6, 8, 24, and 48 h after long-term habituation to the startle response. Antibodies to neurotrophic factors had selective and dose-dependent effects on the different memory and learning processes underlying these types of behavior. Changes in S100b in brain structures were seen, which were specific in terms of quantitative levels and dynamics, after acquisition of the behavioral habit. The results obtained here, along with previously reported data on the effects of antibodies to S100b and CSL given into the cerebellum, are discussed as experimental support for the hypothesis of the heterochronous neurochemical organization of integrative brain activity.

Analysis of Variance↗

Dynamics of intracellular dopamine contents in the rat brain during the formation of conditioned contextual fear and extinction of an acoustic startle reaction.

Extracellular dopamine contents in the caudate nucleus, nucleus accumbens, and prefrontal cortex of the rat brain were measured during two sessions of extinction of an acoustic startle reaction--each consisting of ten sound stimuli, the two sessions separated by 24 h--with simultaneous recording of freezing behavior. The results demonstrated a decrease in extracellular dopamine levels in the caudate nucleus and an increase in the nucleus accumbens during both sessions of extinction, with return to initial immediately after sessions ended. During the second session, the amplitude of startle responses and the magnitude of changes in dopamine levels in both structures were significantly smaller than during the first session. Between the sessions, dopamine levels in the caudate nucleus remained constant, while those in the nucleus accumbens decreased. The prefrontal cortex showed increases in dopamine levels during both sessions of extinction, as well as between the two sessions. The amplitude of the startle reaction was found to correlate with dopamine levels in the prefrontal cortex after the end of the corresponding extinction session and with the dopamine level before the start of the second session. The freezing time before the start of sound stimulation in the second session, this being a measure of conditioned fear, correlated with the dopamine level in the caudate nucleus on the training day and with the dopamine level in the nucleus accumbens before the start of the second session. The role of the dopaminergic system in the mechanisms forming and realizing the various components of defensive behavior are discussed.

Acoustic Stimulation↗

S100B protein in pro- and antiapoptotic doses produces different effects on defensive behavior in adult rats.

We studied the effects of S100b protein in doses stimulating (500 and 50 ng) or inhibiting (5 ng) apoptosis in nerve cells on acquisition, retention, and retrieval of extinction of the acoustic startle response and conditioned fear in adult rats. After application to the vermis of the cerebellum S100b protein in doses of 500 and 50 ng impaired, while in a dose of 5 ng facilitated acquisition of both forms of defensive behavior. Different behavioral effects of S100b protein are probably related to its pro- and antiapoptotic effects on cerebellar cells relevant to the studied forms of behavior. Our results suggest that regulators of apoptosis are involved in the mechanisms of learning and memory.

Acoustic Stimulation↗

[Heterochronic effects of neurotrophic factors in neurochemical organization of learning and memory in the adult organism].

Following elaboration of long-term habituation to a startle-response, antibodies to neurotrophic factor protein S100b exerted selective and dose-dependent influence on different learning processes and memory of learned behavioural patterns in adult rats. S100b increased at all stages of behavioural skill development in hippocampus, hypothalamus, frontal cortex, cerebellar hemispheres and vermis, basal ganglia.

Acoustic Stimulation↗

[Involvement of neurotrophic factors in central mechanisms of behavior in adult animals].

The effect of antibodies against some neurotrophic factors (S-100b protein, CSL, etc.) on elaboration, storage, and retrieval of acoustic startle habituation and concomitant freezing behaviour, was found to be dose-dependent in adult rats. Thus, the 5-mcg dose impaired the consolidation and/or storage process, whereas 2 mcg only impaired the storage of long-term acoustic startle habituation, and 0.5 mcg exerted no effect at all. The habits retrieval displayed no dependence on the antibodies effect.

Acoustic Stimulation↗

Relationship between memory and fear: developmental and pharmacological studies.

Habituation of the acoustic startle response (ASR) and freezing responses were assessed simultaneously in rats of different ages. Results showed that until 30 days of age rats were not able to express long-term habituation of the ASR, whereas irrespective of age, all rats exhibited the increased freezing responses as a result of fear conditioning. In addition, the interaction between fear and memory was studied using the same behavioral model in adult rats treated intraperitoneally with diazepam at doses 1.2 and 2.5 mg/kg. Diazepam administration did not result in a significant change in initial startle responsiveness but elicited a profound suppression of startle amplitude over trials. Furthermore, animals given diazepam showed more initial freezing than the vehicle-treated controls, while fear-conditioned freezing was decreased by diazepam. The pattern of results is discussed in relation to developmental and pharmacological dissociations between the different behavioral components of responses to aversive and stressful cues.

Acoustic Stimulation↗

[The effect of antibodies to S-100 proteins on synaptogenesis processes and learning in rats].

In newborn rats passively immunised with the brain-specific protein (BSP) S-100, obvious ultrastructural changes occurred in the glial cells, density of desmosomal contacts increased and the density of synaptic contacts in neurophile of the supraoptic nuclei of the hypothalamus decreased. The S-100 proteins seem to fulfil a regulatory function in synaptogenesis in both newborn and adult animals.

Animals↗

[Active immunization to exogenous and endogenous antidepressants. The formation of antibodies to biogenic amines and peptide regulators].

The active immunization of rabbits and white rats to antidepressant sydnophen results in the formation of antibodies binding norepinephrine, dophamine, serotonine as well peptide regulatory compounds: substance P, pynorphine, vasopressin and beta-endorphin. The immunization against endogenic antidepressant thyroliberin induces the formation of antibodies to the same biogenic amines and to the gamma-aminobutyric acid, oxytocin and leu encephalin. The data obtained are discussed in connection with some physiological and biochemical changes found earlier during immunization to antidepressants.

Allosteric Regulation↗

Litorin and litorin-albumin conjugate as effective regulators of body temperature in rats.

Intraperitoneal injection of the bombesin-like peptide litorin (0.5 ml of a 10(-5) M solution) led to a short-lived decrease in the body temperature (maximum of 0.9 degrees C) of laboratory rats. In contrast, immunization with litorin conjugated to bovine serum albumin (BSA) led to an increase in body temperature from 36.6 +/- 0.1 to 37.2 +/- 0.1 degrees C that persisted for at least 4 weeks and which was probably due to the binding of endogenous litorin by the newly formed antibody. These results suggest that litorin is involved in the physiological regulation of thermal homeostasis. The temperature of control rats immunized with Freund's adjuvant and BSA without litorin fluctuated around normal at 36.6 +/- 0.1 degrees C over this period. Rat body weight increased evenly during the experiment in both the experimental animals and the two control groups. However, the volume of food intake in the hour following 24 h food deprivation was lower in rats immunized with conjugated litorin than in the control groups.

Animals↗

[Intake of water and sodium chloride solution by the rats after central administration of litorin and immunization with litorin-bovine serum albumin conjugate].

Central injection of litorin suppressed water and sodium chloride solution intake, and also decreased the preference of saline of unrestrained rats during 1 hour test. Active immunization of animals with litorin-bovine serum albumin conjugate led to the augmentation of their daily saline preference. Immunized rats increased also avidity to salt after deprivation, though the consumption volume of liquids decreased. The data, obtained on the immunized animals prove the importance of definite level of endogenous bombesin-like peptide in the salt appetite of rats. The central effect of litorin is discussed in the aspect of changing by it the evaluation of gustatory information.

Animals↗

[Limited proteolysis of brain-specific protein S100. Isolation, physico-chemical and immunochemical characteristics of the neuropeptide AT-1-1].

Six peptides (presumably products of natural protein S100 catabolism) were isolated from bovine brain extracts by hydrophobic chromatography, affinity chromatography on immobilized antiprotein S100 antibodies, gel filtration and chromatography on TSK HW-40 columns in a methanol: water system. At 10(-12) M, peptide AT-I-I caused a 70% inhibition of the specific binding activity of endogenous benzodiazepine brain receptors. When used at higher concentrations (10(-9)-10(-5) M), AT-I-I inhibited the binding activity of central serotonin, dopamine and m-cholinoreceptors. Immunochemical analysis revealed the presence of identical material in rat brain glial cell nuclei (astrocytes). Using a solid phase immunoenzymatic assay, it was shown that peptide AT-I-I was not identical to any other of the 14 peptides tested (commercial preparations). Data from immunochemical analysis testified to the species non-specificity of AT-I-I. It was concluded that in brain tissue natural proteolysis of proteins S100 leads to the formation of biologically active oligopeptide products that are involved, in particular, in the modulation of the functional activity of central benzodiazepine receptors.

Animals↗

Physiologic characterization of novel aggressotropic neuropeptides.

Experimental data of physiological activity of synthetic analogs of three novel neuropeptides isolated from the bovine brain are presented. The characteristics of the influence of the peptides on various forms of aggressivity of rats--intermale, predatory, and defense--with central and peripheral administration, are demonstrated. The influence of the peptides on other types of behavior--the consumption of food and water, fear, locomotor activity--associated with the formation of aggression is demonstrated. The modulatory effects of the peptides on the responses of identified neurons of molluscs to neuromediators, serotonin, dopamine, and glutamate, which participate in the neurochemical support of aggressive behavior of rats, are documented.

Aggression↗

The selective effects of a monoclonal antibody against neural growth-related protein A3G7 on central mechanisms of several types of defensive behavior in adult rats.

Studies were carried out into the effects of monoclonal antibodies to protein A3G7, which is associated with the differentiation of cerebellar and hippocampal neurons, on the development, retention, and reproduction of a habituated acoustic startle response and freezing behavior in rats. Application of monoclonal antibody (50 ng) to the vermis of the cerebellum selectively disrupted the retention of long-term habituation of the acoustic startle response, while a higher dose (5 micrograms) inhibited both retention of long-term habituation of the acoustic startle response and conditioned freezing behavior. Monoclonal antibody (10 micrograms) disrupted the development and retention of short-term and long-term extinction of the acoustic startle response, as well as conditioned freezing behavior. These data provide experimental support for the systemogenesis hypothesis of behavioral acts and for the concept that there is a single molecular basis for development and learning.

Acoustic Stimulation↗

The involvement of neurotrophic factors in the central mechanisms of behavior in adult animals.

In the light of the similarity of the neurochemical mechanisms of behavior during ontogenesis and in adult organisms, studies were performed on the effects of antibodies to neurotrophic factors--S-100b protein, CSL lectin, and R1 lectin-on the acquisition, retention, and reproduction of habituated acoustic startle reactions and freezing behavior in adult rats. Antibodies against neurotrophic factors were found to have selective, dose-dependent effects on the types of behavior investigated. Antibodies to S-100b, CSL, and R1, at a dose of 5 microg, induced derangements in the processes of consolidation and/or retention of behavioral habits. At a dose of 2 microg, antibodies to S-100b selectively blocked the retention of long-term habituation of the startle reaction, while a dose of 0.5 microg had no such effect. Antibodies to neurotrophic factors had no effect on reproduction of acquired defensive habits.

Acoustic Stimulation↗