[Protein-Protein Interactions of Huntingtin in the Hippocampus].

Huntingtin (HTT) occurs in the neuronal cytoplasm and can interact with structural elements of synapses. Huntington's disease (HD) results from pathological expansion of a polyglutamine stretch in the HTT molecule, being probably associated with aberrant protein-protein interactions. The pathogenetic mechanism is still incompletely understood. Alterations of the synaptic structure and plasticity in the hippocampus are observed in early HD. The objective of the study was to theoretically evaluate the HTT contribution to changes in synaptic plasticity by integrating the available experimental data. HTT protein complexes are involved in maintaining the efficiency of synaptic transmission. A pathogenic HTT form (polyQ-HTT) probably disrupts the protein-protein interactions in distorts the dynamics of molecular processes in the synapsis. It was assumed that polyQ-HTT may compete with postsynaptic density proteins and proteins regulating cytoskeleton remodeling.

Amide of Lambertian Acid Suppresses Hyperactivation of Inotropic Glutamate Receptors, but not Synaptic Potentiation in Hippocampal Sections.

Amide of lambertian acid suppresses hyperactivation of inotropic glutamate receptors in hippocampal sections induced by a decrease in the level of magnesium ions (a selective blocker of glutamate NMDA receptors). Treatment of the sections with amide of lambertian acid in standard physiological saline does not prevent development of NMDA-dependent synaptic potentiation. Lambertian acid isolated from needles and turpentine of Siberian pine (Pinus sibirica R. Mayr), and its derivatives may become a source of substances with glutamatergic mechanism of action for treatment of cognitive and neurodegenerative disorders.

[MOBILITY OF AMPA SUBTYPE GLUTAMATE RECEPTOR AS A KEY FACTOR OF EXPRESSION AND MAINTENANCE OF SYNAPTIC POTENTIATION].

A time dynamic of LTP development in the first minutes after high frequency stimulation has been investigated by using a cell model of synaptic potentiation. An experimental assessment of dependence of potentiation and maintenance of a stable level of synaptic transmission in the CA1 area of mice hippocampus on the intracellular transport has been made with brefeldin A (the blocker of transport vesicle forming). The integrative activity of the systems, ensuring the delivery of glutamate receptors to the dendrite spines in amounts and in time intervals necessary for fast changing and long maintenance of transmission efficiency is discussing.

Different effects of α- and γ-glycine on the aberrant activity of pyramidal neurons of hippocampal slices.

Experiments in vitro on hippocampal slices of mouse have shown that solutions prepared from polymorphic modifications α- and γ-glycine have different effect on the aberrant activity of neurons. In the presence of α-glycine the excitability of these neurons decreased more slowly, prolonging its modulating effect on NMDA type glutamate receptors. This effect agrees with higher biological activity of α-polymorphic modifications (as compared with that of the α-form) that previously observed with respect to behavior of mice from the line with genetic diathesis to catalepsy, which were used as a biological model for investigation of some pathological behavior forms.

The correlation between tick (Ixodes persulcatus Sch.) questing behaviour and synganglion neuronal responses to odours.

We examined the behavioural and electrophysiological responses of taiga ticks (Ixodes persulcatus) to several olfactory stimuli: Osmopherone® (5-a-androst-16-en-3-ol), Osmopherine® (butanoic and 3-methylbutanoic acids), DEET® (N,N-diethyl-meta-toluamide), ethanol (96%), and water (control stimulus). To study individual tick behavioural reactions to these stimuli, we used a Y-shaped glass maze (n=50). To study the electrophysiological reactions of the ticks' synganglia to these olfactory stimuli, we recorded the shifts of total potential (TP) of pre-oesophageal neurons in response to odour stimulation of Haller's organ (n=25). We found that Osmopherine® attracted ticks and frequently evoked negative shifts of TP, whereas the response to Osmopherone® did not differ from the reaction to water. DEET® and ethanol acted as tick repellents and generally evoked positive shifts of TP. We also tested each tick for its questing height (QH) on a glass rod that was at an incline of 75°, and we tested for the presence of pathogens i.e., DNA of Borrelia burgdorferi sp. s.l. and RNA of tick-borne encephalitis virus (TBEV). The degree of response to Osmopherine® positively correlated with the QH. The ticks with the highest values of QH showed a greater prevalence of the tick-borne pathogen Borrelia sp. s.l. compared with the ticks that did not reach the maximum QH. The present results show a correlation between the electrophysiological reaction of the synganglia of ticks and their behavioural responses to different odours.

[Influence of terahertz (submillimeter) laser radiation on neurons in vitro].

The development of new sources of coherent non-ionizing radiation in terahertz wave range put forward the basic problems of revealing the mechanism of its action on biological objects, especially, on the nervous system. At this point it is necessary to reveal the radiation effects on complex molecular systems such as nerve cells. It was the main objective of this study. In the previous study we were the first to demonstrate highly specific effects of some examined wavelengths on the structural-functional properties of the nerve cells. The radiation of a free-electron laser produced damage to neuron morphology dependent on the power and wavelength. Transparent blank protrusions of the membrane, disorders of the growth of processes, and fall of the membrane potential were observed. The model developed and the data obtained approach the understanding of the molecular mechanisms of the effect of the waves under study on cells. These waves can be probably used as a tool for further investigation of functioning of neurons and neural system and correction of some pathology.

Substances in subthreshold concentrations under stress conditions can act as conditioned stimuli and trigger defense reactions.

The capacity of living systems to perceive low-intensity stimuli sometimes inducing protective reactions is still little studied. Incubation of neurons under conditions increasing the content of cAMP and Ca(2+) increases the amplitude of their responses to lidocaine (10(-3) M). After cell preconditioning with low concentrations of lidocaine (10(-15) M) under these conditions, the protective effects of "ineffective" concentrations were detected, because the response amplitude did not decrease. It was hypothesized that the basic amplitude responses retrieved by lidocaine in a concentration of 10(-3) M are memory traces about the effects of this compound in subthreshold concentrations.

Effects of histochrom and emoxypin on biophysical properties of electroexitable cells.

Comparative investigation of effects of antioxidant agents histochrom and emoxypin on biophysical characteristics of isolated neurons from shell Lymnaea stagnalis under normal conditions and during oxidative stress was performed. Differently directed effects of these compounds on resting potential and transmembrane ion currents of neural cells under normal conditions were detected. Histochrom provides hyperpolarizing and emoxypin--depolarizing effect on neuronal membrane potential. Under conditions of oxidative stress both products possess antioxidant action. Obtained data allows coming closer to understanding of cellular-molecular mechanisms of protective action of compounds.

Epileptiform activity in the hippocampus of mice with different predisposition to pinch catalepsy.

Experiments on hippocampal slices of CBA mice showed that the probability of spontaneous epileptiform discharges recorded in the field CA1 pyramidal layer is higher in animals predisposed to catalepsy compared to mice with low predisposition to catalepsy. Presumably, some factors determining predisposition to catalepsy modulate synchronization of neuronal activity in the hippocampus; this suggests using hippocampal slices as a model for studies of neurophysiological mechanisms of hereditary predisposition to catalepsy.

Plasticity of neuronal responses induced by low concentrations of exogenous ligands affecting cellular calcium stores.

Modification of reactions caused by repeated influences (plasticity) is a fundamental property of cell. In this study, we have revealed effects of low concentrations of two exogenous modulators of cellular processes (caffeine and cyclosporin A) on neuronal plastic properties. The study was carried out on isolated neurons of Lymnaea stagnalis. It was found that low concentrations of caffeine or cyclosporin A did not cause any changes of the membrane potential (MP) of isolated neurons. However, pretreatment of neurons with low concentrations of caffeine or cyclosporin A reduced the amplitude of MP changes caused by the action of physiological concentrations of these ligands on the average by 30.8% and 29.1%, respectively. The findings permitted implying a significant role of low ligand concentrations in the formation of cell memory and neuronal plastic properties.

Reaction of neurons to alkaloid agonists of opioid receptors during modulation of phosphodiesterases.

We studied the effect of ultralow doses of theophylline and morphine, modulators of receptors and intracellular signal systems, on ion permeability of membranes. Theophylline and morphine in ultralow doses blocked the neuronal responses to these agents applied in physiological concentrations. Theophylline in ultralow doses attenuated, but did not completely block neuronal reaction to morphine. These findings suggest that ultralow doses of various substances producing no appreciable physiological changes can activate mechanisms providing optimum response to strong factors.

The effects of the dynamic state of the cytoskeleton on neuronal plasticity.

The effects of degrading and stabilizing microtubules and microfilaments on the formation of plastic reactions were studied in isolated nerve cells from the mollusk Lymnaea stagnalis. Degradation of the cytoskeleton affected the performance, retention, and repeated acquisition of plastic reactions. Stabilization of microtubules led to the appearance of a relationship between the dynamics of the development and retention of plastic reactions and the series of stimulation. Stabilization of microfilaments led to transient plastic reaction, along with long-term reactions. These results show that rearrangements of the cytoskeleton have a key role in the processes of neuronal plasticity.

[Effect of the cytoskeleton dynamic condition on the neuronal plasticity]. / Vliianie dinamicheskogo sostoianiia tsitoskeleta na neironal'nuiu plastichnost'.

Infringement of the Lymnaea stagnalis cytoskeleton condition affected preservation and repeated development of plastic responses. Stabilising of the microtubules led to a dependence of the development and preservation dynamics of the plastic responses. Stabilising of the microfilaments transformed short-term plastic responses into long-term ones. The findings suggest a key role of reorganisation of the cytoskeleton in neuronal plasticity.

Effects of changes in dynamic equilibrium in microtubule and microfilament systems on the plastic responses of neurons.

Studies were carried out on the effects of disruption and stabilization of microtubules and microfilaments on the formation of neuronal plastic responses in isolated nerve cells of the mollusk Lymnaea stagnalis. Disruption of these cytoskeletal elements prevented the development of neuronal plastic responses. Microtubule stabilization produced a dynamic relationship between the development and retention of neuronal plastic responses and series of stimuli. Stabilization of microfilaments blocked the development but promoted the retention of these neuronal responses.

[The effect of changes in the dynamic equilibrium in the microtubular and microfilamentous systems on neuronal plastic reactions]. / Vliianie izmeneniia dinamicheskogo ravnovesiia v sistemakh mikrotrubochek i mikrofilamentov na plasticheskie reaktsii neirona.

Effects of disruption or stabilization of microfilaments or microtubules on formation of neuronal plastic reactions (NPR) were studied in isolated Lymnaea stagnalis neurons. Disruption of these cytoskeletal elements blocked the development of the NPR. After stabilization of the microtubules the dynamics of development and retention of the NPR became dependent on the stimulation series. Stabilization of the microfilaments blocked the development but improved the retention of the NPR. The role of the dynamic cytoskeletal reorganization in the process of NPR formation is discussed on the basis of the obtained data.

[Changes in the neural activity of the blood serum from patients with ischemic heart disease]. / Izmenenie neiroaktivnosti syvorotki krovi u patsientov pri ishemicheskoi bolezni serdtsa.

The isolated neurons of snail (Lymnaea stagnalis) were as test object for the evaluation of the blood serum neuroactivity. The blood serum was tested before treatment and after six applications of intravenous laser therapy (ILT). All blood serum specimens produced depolarization of the cell membrane potential. The quantitative comparison of membrane toxicity of control and experimental blood serum specimens permitted to divide the patients into three groups. Blood serum (after six applications of ILT of patients from the first and second groups produced a lower membrane toxicity effect on neurons. In the groups the membrane toxicity effect decrease by 43% +/- 10.3 and 7.3 +/- 2.2% respectively. In third group the membrane toxicity effect increased by 21.5 +/- 4.5. All patients from the third group had myocardial infarction less than one year before being given a course on the treatment. The ILT was found to be able to decrease the activity of the blood serum components disrupting normal functioning of the ionic mechanisms of cell membranes.