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.

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.

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.

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 influence of exogenous gangliosides on the dynamics of the development of prolonged posttetanic potentiation.

The influence of various gangliosides on the dynamics of the development of prolonged posttetanic potentiation (PPTP) in the layer of pyramidal cells of field CA3 during the stimulation of mossy fibers was investigated in rat hippocampus section. It was demonstrated that the GM1 and GD1b gangliosides stimulate the induction and maintenance of PPTP to varying degrees and that GD1a and GT1b inhibit the phase of maintenance as compared with the active control. A conclusion was reached regarding the participation of gangliosides in the mechanisms of synaptic plasticity.

Alterations in calmodulin and S-100 protein content of hippocampal slices during long-term potentiation.

The content of calmodulin and S-100 protein in fractions of rat hippocampal slices was assayed by solid phase radioimmunology and radial immunodiffusion, respectively. One hour after tetanization (electrical stimulation of area dentata granular cells and recording from CA3 pyramids) an inverse translocation of these Ca++-binding proteins was observed: an increase in the calmodulin content in the water-soluble and a decrease in the Lubrol-soluble fractions, while an increase in S-100 protein in the Triton-soluble and a decrease in the water-soluble fractions occurred. The results are suggestive of a regulatory function of these proteins in events during repetitive stimulation of a synaptic input. The calmodulin increase in the cytosolic compartment may reflect the involvement of Ca++-calmodulin dependent intraneuronal metabolic processes underlying the induction and/or temporary maintenance of neuronal functional changes occurring after repeated or intense synaptic activity. The elevated S-100 protein level in the membrane compartment might be interpreted in terms of functionally induced redistribution in that neuronal cells are provided with additional amounts of S-100 protein originating from the surrounding glial cells which store large amounts of soluble S-100 protein.