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Biomedical subjects

N V Gulyaeva

Publications and source records attributed to N V Gulyaeva.

At least 19 recordsLinked to original sources
PubMed2006

Studies of the effects of central administration of beta-amyloid peptide (25-35): pathomorphological changes in the Hippocampus and impairment of spatial memory.

The possible link between amnesia induced by central administration of beta-amyloid (25-35) (Abeta(25-35)) and neurodegenerative changes in the hippocampus was studied. Male Wistar rats received single intracerebroventricular injections of Abeta(25-35) at a dose of 15 nmoles and one month later were trained in an eight-arm radial maze. Training was followed by histological assessment of the state of the hippocampus on brain sections stained with hematoxylin and eosin. Abeta(25-35) induced impairments in long-term (reference) and working memory on testing in the maze. There was a moderate reduction in the number of neurons in hippocampal field CA1; there was no change in the number of cells in field CA3. The numbers of errors made by the animals on testing in the maze were found to correlate negatively with the numbers of nerve cells in hippocampal field CA1. Thus, this is the first demonstration that impairments of learning and memory induced by single doses of Abeta(25-35) are specifically associated with neurodegenerative changes in hippocampal field CA1 in rats.

Amyloid beta-Peptides↗
PubMed2006

Pentylenetetrazol kindling in rats: Is neurodegeneration associated with manifestations of convulsive activity?

Structural changes in neurons and measures of oxidative stress were studied in the hippocampus of rats tolerant (ST) and sensitive (SS) to developing clonic-tonic seizures in conditions of pentylenetetrazol kindling. Sequences of 11 injections of pentylenetetrazol significantly decreased the number of normal neurons in hippocampal field CA1 in SS rats, this effect being seen in both hippocampal field CA1 and the dentate fascia in ST rats. Decreases in the numbers of normal neurons were accompanied by increases in the numbers of damaged cells in field CA4 in rats of both groups. After 21 injections, decreases in the numbers of normal neurons were seen in field CA1 in both SS and ST rats, while the numbers of damaged neurons were significantly greater than control only in ST rats in fields CA1 and CA4. The glutathione level was significantly lower in the hippocampus in both groups of rats than in controls. Thus, rats " tolerant" to developing convulsions show signs of oxidative stress and neurodegenerative changes in the hippocampus. This suggests that oxidative neuron damage leading to neurodegeneration in the pentylenetetrazol kindling model is not directly associated with convulsive activity.

Animals↗
PubMed2006

Long-term potentiation in the hippocampus in conditions of inhibition of caspase-3: analysis of facilitation in paired-pulse stimulation.

Treatment of hippocampal slices with the caspase-3 inhibitor Z-DEVD-FMK led to a decrease in the magnitude of long-term potentiation (LTP), which developed over time. Testing with paired stimuli separated by an interval of 70 msec showed that after caspase-3 inhibition, as compared with control slices, the second response in the pair showed no increase in amplitude in conditions of LTP. In these conditions, the magnitude of LTP depended on differences in the amplitudes of the first and second responses before induction of LTP. LTP was absent in slices with initially highly efficient afferent stimulation and correspondingly low levels of facilitation in paired-pulse stimulation. It is suggested that inhibition of caspase-3 prevents the structural rearrangements in LTP associated with the involvement of new synapses and neurons in the response.

Analysis of Variance↗
PubMed2006

Caspase-like activity is essential for long-term synaptic plasticity in the terrestrial snail Helix.

Although caspase activity in the nervous system of mollusks has not been described before, we suggested that these cysteine proteases might be involved in the phenomena of neuroplasticity in mollusks. We directly measured caspase-3 (DEVDase) activity in the Helix lucorum central nervous system (CNS) using a fluorometrical approach and showed that the caspase-3-like immunoreactivity is present in the central neurons of Helix. Western blots revealed the presence of caspase-3-immunoreactive proteins with a molecular mass of 29 kDa. Staurosporin application, routinely used to induce apoptosis in mammalian neurons through the activating cleavage of caspase-3, did not result in the appearance of a smaller subunit corresponding to the active caspase in the snail. However, it did increase the enzyme activity in the snail CNS. This suggests differences in the regulation of caspase-3 activity in mammals and snails. In the snail CNS, the caspase homolog seems to possess an active center without activating cleavage typical for mammals. In electrophysiological experiments with identified snail neurons, selective blockade of the caspase-3 with the irreversible and cell-permeable inhibitor of caspase-3 N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp-(OMe)-fluoro-methylketone prevented development of the long-term stage of synaptic input sensitization, suggesting that caspase is necessary for normal synaptic plasticity in snails. The results of our study give the first direct evidence that the caspase-3-like activity is essential for long-term plasticity in the invertebrate neurons. This activity is presumably involved in removing inhibitory constraints on the storage of long-term memory.

Animals↗
PubMed2005

Central administration of a caspase inhibitor impairs shuttle-box performance in rats.

Recent studies suggest that caspase-3-mediated mechanisms are essential for neuronal plasticity. N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val- Asp(OMe)-fluoromethyl ketone (z-DEVD-fmk), a caspase inhibitor with predominant specificity toward caspase-3, has been shown to block long-term potentiation in hippocampal slices. Intrahippocampal infusion of a caspase-3 inhibitor to rats has been shown to significantly impair spatial memory in the water maze. The present work was designed to study whether i.c.v. administration of a caspase-3 inhibitor z-DEVD-fmk impairs learning in other tasks related to specific forms of memory in rats. The rats received bilateral injections of z-DEVD-fmk or N-benzyloxycarbonyl-Phe-Ala-fluoromethyl ketone (z-FA-fmk) ("control" peptide) at a dose of 3 nmol. Administration of z-DEVD-fmk significantly decreased the number of avoidance reactions in some blocks of trials in the active avoidance (shuttle box) learning, while z-FA-fmk had no effect as compared with intact rats. However, only a slight effect of the caspase inhibitor across the session was found. z-DEVD-fmk impaired development of some essential components of the two-way active avoidance performance, such as escape reaction, conditioned fear reaction, and inter-trial crossings. Measurement of caspase-3 activity in rat brain regions involved in active avoidance learning revealed most expressed z-DEVD-fmk-related inhibition of the enzyme activity (about 30%) in the fronto-parietal cortex. A similar effect was close to significant in the hippocampus, but not in the other cerebral structures studied. In primary cultures of cerebellar neurons z-DEVD-fmk (2-50 microM) inhibited caspase-3 activity by 60-87%. We suggest that moderate inhibition of caspase-3 resulting from the central administration of z-DEVD-fmk to rats may impair active avoidance learning. Taking into account previous data on the involvement of neuronal caspase-3 in neuroplasticity phenomena we assume that the enzyme may be important for selected forms of learning.

Animals↗
PubMed2005

Actions of pulsed ultra-broadband electromagnetic irradiation on the EEG and sleep in laboratory animals.

Irradiation of animals with ultrashort impulses of ultra-broadband magnetic irradiation with an impulse repetition frequency of 6 Hz for 1 h induced changes in the spectral composition of cerebral cortex electrical activity in rats, measured over the 5 min immediately after irradiation, as compared with controls. In particular, there was suppression of frequencies close to the impulse sequence frequency, along with a decrease in interhemisphere coherence. Continuous recording of polygrams for 22 h from rabbits after irradiation revealed a "delayed" effect--a significant increase in paradoxical sleep, starting 16 h after the end of irradiation and persisting to the end of the recording period. It is suggested that irradiation has a direct action both on the mechanisms of generation of the theta rhythm (septohippocampal) and on the system controlling circadian rhythms (the suprachiasmatic nucleus-epiphysis system).

Acoustic Stimulation↗
PubMed2005

Studies of the effects of fragment (25-35) of beta-amyloid peptide on the behavior of rats in a radial maze.

Decreases in cognitive functions, particularly long-term (episodic) and working memory, are among the earliest prognostic signs of Alzheimer's disease. The toxicity of beta-amyloid peptide is regarded as a major cause of neurodegeneration and cognitive impairment in this disease. The present report describes studies of the effects of intracerebroventricular administration of beta-amyloid peptide (25-35) (Abeta(25-35)) on the reproduction of a previously assimilated habit consisting of finding food in an eight-arm radial maze in rats. Abeta(25-35) was given bilaterally at doses of 15 and 30 nmol/animal seven days after preliminary training. Testing was performed 60 days after peptide administration. The results showed that Abeta(25-35) impaired working memory in rats without having any significant effect on the retention of responses. We were unable to demonstrate any relationship between memory impairment and the dose of peptide given. These data provide evidence of the ability of Abeta(25-35) to produce greater degradation of working memory function than long-term memory function.

Amyloid beta-Peptides↗
PubMed2005

Electroconvulsive shock induces neuron death in the mouse hippocampus: correlation of neurodegeneration with convulsive activity.

The relationship between convulsive activity evoked by repeated electric shocks and structural changes in the hippocampus of Balb/C mice was studied. Brains were fixed two and seven days after the completion of electric shocks, and sections were stained by the Nissl method and immunohistochemically for apoptotic nuclei (the TUNEL method). In addition, the activity of caspase-3, the key enzyme of apoptosis, was measured in brain areas immediately after completion of electric shocks. The number of neurons decreased significantly in field CA1 and the dentate fascia, but not in hippocampal field CA3. The numbers of cells in CA1 and CA3 were inversely correlated with the intensity of convulsions. Signs of apoptotic neuron death were not seen, while caspase-3 activity was significantly decreased in the hippocampus after electric shocks. These data support the notion that functional changes affect neurons after electric shock and deepen our understanding of this view, providing direct evidence that there are moderate (up to 10%) but significant levels of neuron death in defined areas of the hippocampus. Inverse correlations of the numbers of cells with the extent of convulsive activity suggest that the main cause of neuron death is convulsions evoked by electric shocks.

Animals↗
PubMed2004

Inhibition of caspase-3 blocks long-term potentiation in hippocampal slices.

Incubation of rat hippocampal slices with the specific caspase-3 inhibitor Z-DEVD-FMK led to suppression of long-term potentiation (LTP), which developed over a period of time. Incubation of Z-DEVD-FMK for 4 h and more prevented tetanization from evoking LTP; Z-DEVD-FMK had no effect on baseline measures of synaptic plasticity and short-term plasticity (population spike amplitude, level of facilitation in conditions of paired stimuli). These data provide the first evidence for the involvement of a mechanism mediated by caspase-3 in the phenomenon of LTP.

Analysis of Variance↗
PubMed2003

Single intracerebroventricular administration of amyloid-beta (25-35) peptide induces impairment in short-term rather than long-term memory in rats.

Ample experimental evidence indicates that intracerebral injection or infusion of amyloid-beta peptides (Abeta) to rodents induces learning and memory impairments as well as neurodegeneration in brain areas related to cognitive function. In the present study, we assessed the effects of a single intracerebroventricular (i.c.v.) injection of aggregated Abeta fragment (25-35) at a dose of 15nmol/rat on short-term and long-term memory in rats during the 6-month post-surgery period. The results demonstrate that Abeta(25-35)-induced memory impairments in spontaneous alternation behavior in a Y-maze at 17, 36, and 180 days after the surgery as well as in a social recognition task 110 days post-surgery. Abeta(25-35) also impaired spatial memory in an 8-arm radial maze, but did not influence performance of the step-down passive avoidance task. These results suggest that Abeta(25-35) preferably induces impairments of spatial and non-spatial short-term (working) memory rather than long-term memory in rats.

Amyloid beta-Peptides↗
PubMed2003

Administration of aggregated beta-amyloid peptide (25-35) induces changes in long-term potentiation in the hippocampus in vivo.

Intracereroventricular administration of aggregated beta-amyloid protein fragment (25-35) (7.5 nmol/ventricle) was followed one month later by significant changes in the dynamics of long-term potentiation in the hippocampus in vivo, expressed as powerful and stable increases in the amplitude of evoked potentials. This phenomenon may be associated with oxidative stress in the hippocampus, which has previously been demonstrated in this model, and, thus, with disturbances in ion homeostasis.

Amyloid beta-Peptides↗
PubMed2003

Analysis of cyclic adenosine-3',5'-monophosphate levels in structures of the "informational" and "motivational" systems of the rat brain during acquisition of a conditioned active avoidance reaction.

Cyclic adenosine-3'5'-monophosphate (cAMP) levels in structures of the "informational" and "motivational" systems of the brain were measured during acquisition of a conditioned two-sided active avoidance reflex in rats. cAMP levels were measured in three groups of animals--intact animals, trained animals, and an active control group (given uncombined presentations of the conditioned (light) and unconditioned (electric shock) stimuli)--immediately after reproduction of the acquired reflex. Significant accumulation of cAMP levels in brain structures was seen in animals of the active control group in the hypothalamus and in trained animals in the left and right hippocampus and the right frontal cortex. Positive correlations were found between cAMP levels in symmetrical parts of the frontal cortex, amygdala, and hypothalamus in animals of all study groups. In addition, active control rats and trained rats showed interhemisphere and intrahemisphere correlations between cAMP levels in brain macrostructure, whose patterns were specific for each group. The pattern of correlations observed here is assessed from the point of view of the role of the "informational" and "motivational" structures in the organization of adaptive behavior.

Amygdala↗
PubMed2003

Non-apoptotic functions of caspase-3 in nervous tissue.

Some enzymes that have been recognized as "apoptotic" so far may be involved in important cellular processes not necessarily related to cell death in nervous tissue. The activity of caspase-3, an "apoptotic" enzyme, can be measured in normally functioning neurons. The results reported by several groups point to the possibility that caspases may be involved in nervous tissue function as top enzymes in the regulatory proteolytic cascade. A concept on a new mechanism of synaptic plasticity modulation involving caspase-3 has been formulated postulating a specific role of caspase-3 in normal brain functioning. The idea of synaptic plasticity modulation by caspase-3 is in line with data reported recently. For example, caspase-3 is possibly involved in the long-term potentiation (LTP) phenomenon since proteins that are key players of molecular mechanisms of LTP induction and maintenance are caspase-3 substrates. Experimental results on blocking LTP by a caspase-3 inhibitor confirm this concept.

Animals↗
PubMed2003

Nitric oxide synthase activity in Fasciola hepatica: a radiometric study.

The activity of neuronal nitric oxide synthase (nNOS) in homogenates of adult Fasciola hepatica was measured by the direct radiometric assay of the production of L-[3H]citrulline. This is the first radiometric study of the activity of nNOS in a fluke. The effect of arginase was tested. In the presence of L-valine, which is an inhibitor of arginase, the formation of L-[3H]citrulline decreased from 12% to 38%, depending on the time of incubation. This means that the arginase activity in the worm is high, and has to be taken into consideration when measuring the activity of nNOS. When co-factors, such as H4B, and NADPH, were omitted the formation of L-[3H]citrulline decreased significantly (29%). The effects of several nNOS inhibitors were tested. N(omega)-nitro-L-arginine (L-NAME), aminoguanidine and S-methyl-L-thiocitrulline added at a concentration of 1 mM inhibited the L-[3H]citrulline formation by 28%, 15% and 14%, respectively. Chelation of Ca2+ with 1 mM EGTA resulted in a 40% decrease in the formation of L-[3H]citrulline. These results indicate the presence of nNOS activity in homogenates of F. hepatica.

Animals↗
PubMed2001

Periods of postnatal maturation of hippocampus: synaptic modifications and neuronal disconnection.

The paired-pulse paradigm was used to study the maturation of CA1 population spikes (PS) in the hippocampal slices of Wistar rats. Measurements were taken daily, from postnatal day (PN) 14 to PN27. In the slices from younger animals, inputs exhibit strong paired-pulse profile, which may be associated with low synaptic efficacy. Both responses increased during the third week of life, however, PS1 increased faster so that the PS1/PS2 ratio increased during the early period and remained increased thereafter. This may reflect postnatal modifications of synaptic transmission mediating the increase in hippocampal responses. Modifications of synaptic efficacy are prevailing during early phases while other mechanisms take over at later stages. Partial correlation analysis suggests that the decline of PS amplitude after PN19 may be due to the decrease in the number of connected neurons rather than to modifications of the synaptic efficacy. Thus, the actual direction and magnitude of postnatal PS maturation is suggested to depend on the balance of these two factors. The transient decline of PS amplitude coincided with a period of caspase-3 activation. There was a clear general trend for caspase-3 activity to decrease before PN17, while the inverse trend was observed during next period up to PN21.

Action Potentials↗
PubMed2001

Synaptic vesicle acidification and exocytosis studied with acridine orange fluorescence in rat brain synaptosomes.

The acidification of synaptic vesicles (SV) in rat brain synaptosomes was studied using acridine orange (AO) as a fluorescent probe. In synaptosomal suspensions the AO fluorescence was partially quenched, indicating the presence of an acidic compartment. In permeabilized synaptosomes, the quenching was augmented by MgATP and was sensitive to concanamycin A, a specific inhibitor of the V-type H(+)-ATPase known to be present in synaptic vesicles. Some ATP-dependent acidification was also observed without permeabilization, suggesting that a fraction of synaptosomes (ca. 15%) was unsealed, irrespective of the method used to prepare the synaptosomes (sucrose or Ficoll density gradient, sedimentation or flotation). Depolarization of synaptosomes with 30 mM KCl resulted in an immediate, albeit small, rise in AO fluorescence that was prevented by the removal of Ca(2+) or by substituting NaCl for KCl. This response is consistent with depolarization-evoked release of the acidic contents of an exocytosis-competent pool of synaptic vesicles, representing ca. 5% of the total. No further AO release subsequent to the immediate phase was observed in depolarized synaptosomes, which indicates an extremely rapid reacidification. The results demonstrate that AO fluorescence is suitable for monitoring SV acidification within synaptosomes, and may be used to derive an independent estimate of the relative size of the immediately releasable SV pool. In addition, the use of AO might be advantageous for the assessment of synaptosomal integrity by comparing the ATP-dependent acidification in intact and permeabilized synaptosomes.

Acids↗