[Systemic control of the molecular, cell, and epigenetic mechanisms of long-lasting consequences of stress].

Based on M.E. Lobashev's views of the systemic control of genetic and cytogeneitc processes and a substantial effect of excitability on plastic changes in the central nervous system (CNS), the effect of prolonged emotional and pain stress (PEPS) on the molecular, cell, and epigenetic mechanisms of injury memory was studied in rat strains bred for a certain excitability of the nervous system. PEPS was for the first time found to cause long-lasting (2 months) morphological alterations of the CA3 region of the hippocampus and to modify the genome activity of its pyramidal neurons. The two phenomena were potentiated by a genetically determined low functional state of the CNS. The post-stress regulation of the genome function in hippocampal neurons was mediated by changes in heterochromatin conformation, activation of methyl-CpG-binding protein (MeCP2) synthesis, and subsequent changes in acetylation of histone H4. Genetically determined high excitability of the nervous system proved to be a risk factor that affects the specifics and time course of the observed molecular, cell, and genetic transformations of neurons. The results provide for a better understanding of the epigenetic mechanisms of injury memory, which forms a pathogenetic basis for posttraumatic stress disorder and other human psychogenic conditions characterized by a prolonged duration.

[Numerical density of neurons in the hippocampus of rat lines contrasting in excitability of the nervous system exposed to prolonged emotional painful stress].

Two lines of rats, selected according to the excitability of nervous system to the action of an electric current, served as the model objects to study the changes of numerical density of neurons in hippocampus area CA3 24 hours, 2 weeks, 2 and 6 months after prolonged exposure to emotional painful stress. Reduction of neuron density in hippocampus area CA3 was demonstrated after exposure to stress that persisted as long as 6 months. These changes developed following time intervals that were different for each line of rats (24 hours for rats with low excitability and 2 month--for rats with high excitability). Thus, it was demonstrated for the first time, that prolonged differential effect of stress on numerical density of neurons in hippocampus area CA3, that plays an important role in the processes of learning and memory, depends on genetically determined constitutional peculiarities of the nervous system.

[Branched form of the encapsulated dermal receptors in rats]. / Vetviashchaiasia forma inkapsulirovannykh retseptorov kozhi krys.

Using electron microscope the receptors found in the zone of highest receptor sensitivity in the skin fold at the base of IV finger of rat hind limb were studied. These receptors are represented by complex incapsulated corpuscles consisting of a group of small endings similar to Pacinian corpuscles, which are densely packed and surrounded by a common connective tissue capsule. Each single primary receptor is provided with an unmyelinated receptor terminal, analogue of internal bulb, and a multilayered external bulb. Primary receptor differs from Vater-Pacinian corpuscle by a significantly smaller size, form of sensitive terminal in cross-section, small number of layers forming internal and external bulbs. Complex corpuscle is the derivative of n. tibialis myelinated sensory fiber. The later is divided after the loss of myelin forming a platform of division with several (up to 5) short sprouts and separate incapsulated receptors at their ends. The complex corpuscles described apparently are dermal mechanoreceptors.

[Metallophilia in the Ranvier's nodes of nerve fibers in rats of different strains (histochemical study)]. / Metallofiliia uzlovykh perekhvatov nervnykh volokon u krys razlichnykh linii (gistokhimicheskoe issledovanie)

Myelinated nerve fibers formed by the processes of LV spinal ganglion neurons were studied in two lines of rats selected according to high and low thresholds of nerve system excitability to electric current. Before ultrastructural study the fibres have been treated with potassium pyroantimonate. It was demonstrated that specific dense precipitate was deposited in the nodes of Ranvier of the nerve fibers of rats with low excitability thresholds; this precipitate was not found in the fibers of rats with high thresholds. It is suggested that deposition of precipitate is indicative of a high density of sodium channels in neurilemma, i.e. of high functional activity of nerve fibers.

[Characteristics of heterochromatin of heterophase nuclei from interphase neurons of various brain structures selected for the nervous system excitability]. / Kharakteristika geterokhromatina interfaznykh iader neironov razlichnykh struktur golovnogo mozga krys, selektirovannykh po vozbudimosti nervnoi sistemy.

Quantitative characteristics (the area and number of chromocenters) of the interphase C-heterochromatin in the nuclei of pyramidal neurons of the midbrain reticular formation, sensorimotor cortex, and hippocampus (CA3) of rat strains with different genetically determined excitability were studied in the normal state of the animals and after exposure to a short-term emotional pain stress. The results indicate a relationship between the excitability of the nervous system and structural-functional state of the neuronal interphase heterochromatin. The role of cytogenetic features of different brain structures in the CNS functioning and behavior and their relation with genetically determined excitability of the nervous system are discussed.

[Single-strand DNA breaks in brain cells of different rat strains under normal condition and during exposure to stress]. / Odnonitevye razryvy DNK v otdel'nykh kletkakh mozga razlichnykh linii krys v norme i pri stressornom vozdeistvii.

This study was aimed to characterize pattern of occurrence of spontaneous single-strand breaks in situ in glial and neuronal nuclei of the cortex, middle brain and hyppocapmi (CA3 field) of rats selected for a threshold of nervous system excitability, and to study the influence of stress of various modality on such breaks. The results obtained evidence that: 1) intact animals possess a subpopulation of glial and neuronal cells revealed following gap filling in situ in opposite to other types of terminally differentiated non-proliferating cells; 2) the size of such a subpopulation differs depending on the lines of examined rats, parts of brain, and the type of stress.

[Proliferative activity and structure-functional organization of chromosomes in cells from the developing brain in respect to genetically determined excitability of the rat nervous system]. / Proliferativnaia aktivnost' i osobennosti strukturno-funktsional'noi organizatsii khromosom v kletkakh razvivaiushchegosia mozga v sviazi s geneticheski determinirovannoi vozbudimost'iu nervnoi sistemy u krys.

Neuroblasts of developing hippocampus of 16-17-day old rat embryo of the line with high threshold excitability are characterised by a high level of proliferative activity and chromosome aberration, as well as high degree of brain chromatin concentration as compared with embryos of a line with low threshold excitability.

[Changes in secretion of sex steroid hormones during stress in rats with various brain excitability]. / Izmenenie sekretsii polovykh steroidnykh gormonov pri stresse u krys s raznoi vozbudimost'iu mozga.

A stress procedure decreased the plasma progesterone faster in highly excitable rats than in the less excitable those. The decrease in gonadal and adrenal progesterone was still obvious in 24 hours in both groups of rats but more obvious in the former group in respect to the progesterone level. The data obtained may help to understand individual ability to respond to a stress in a different way depending on functional condition of the hypothalamo-pituitary-adrenal axis.

[Changes in phosphoinositide metabolism in the brain of rats with different neuromuscular excitation threshold subjected to neurotic exposure and antioxidant administration]. / Izmeneniia metabolizma fosfoinozitidov v mozgu krys, razlichaiushchikhsia po porogu nervno-myshechnoi vozbudimosti, pri nevrotiziruiushchem vozdeistvii i pri deistvii antioksidanta.

No difference was found in metabolism of phosphoinositides in rats with high (H) and low (L) levels of excitability under normal conditions. Neurotisation decreased the content of phosphotidilinositol-4,5-diphosphate and increased the phosphorus turnover rate in the brain cortex of the L rats. Oxymetacyl reduced the effect of neurotisation. This antioxidants seems to exert an effect on the brain cells functional condition in the L rats.

[Frequency of chromosome aberrations induced by a single exposure to stress in rats selected for excitability of the nervous system]. / Chastota khromosomnykh narushenii, indutsirovannykh odnokratnym stressornym vozdeistviem u krys, selektirovannykh po vozbudimosti nervnoi sistemy.

The effect of short-term emotional and algesic stress on chromosomal aberration rate in bone marrow cells was studied in four lines of rats selected for excitability of the nervous system. The exposure induced an increase in chromosomal aberration rate only in highly excitable animals; the effect was classified as a low mutagenic. Possible mechanisms of the effect of stress factors on the chromosomal apparatus of cells are discussed.

[Ultrastructural changes in the encapsulated nerve endings of the tibial nerve under the action of diethyl ether in 2 strains of rats selected for their threshold of nervous system excitability]. / Izmenenie ul'trastruktury inkapsulirovannykh nervnykh okonchanii bol'shebertsovogo nerva pod deistviem diétilovogo éfira u dvukh linii krys, selektirovannykh po porogu vozbudimosti nervnoi sistemy.

Ultrastructure of tibial nerve receptor endings was studied in two rat lines different in the threshold of the nerve excitation after decapitation and euthanasia with diethyl ether use. Interlinear diversities of shape and parameters of receptor endings and their mitochondria were established. The results obtained indicate different reactivity of rats varying in genetically determined nervous system excitation threshold to tissue respiration decrease and oxygen insufficiency on ultramicroscopic levels.

[The effect of neurotization after a long period following its termination on the behavior of rats differing by nervous system excitability]. / Vliianie nevrotizatsii spustia dlitel'nye sroki posle ee okonchaniia na povedenie krys, razlichaiushchikhsia po vozbudimosti nervnoi sistemy.

Behaviour of two strains of rats with high and low levels of excitability of the nervous system was studied in 6 months after the end of neurotization and compared with that of the intact (control) rats. Stable disturbances were revealed in behavioural components which were initially characteristic for each strain of rats. In rats with the high threshold of nervous excitability the emotional component of behaviour was disturbed and in those with the low threshold the motor disorders were observed.

[The characteristics of the effects of morphine and naloxone in rat strains differing by the excitability thresholds of their nervous systems]. / Osobennosti éffektov morfina i naloksona u linii krys, razlichaiushchikhsia po porogu vozbudimosti nervnoi sistemy.

Effect of morphine and naloxone on nociceptive sensitivity were studied in 3 rat strains, with high, low, and intermediate thresholds of nervous system excitability. The highest sensitivity to morphine correlated with its dose dependence was revealed in rats with low and high thresholds of excitability. The lowest sensitivity was found in rats with intermediate thresholds of excitability. The obtained data led to the conclusion about essential contribution of genetical control of excitability in the mechanisms of functioning of the opiate system.

[Spiramycin (rovamycin), a macrolide antibiotic for oral treatment of outpatient pneumonia]. / Spiramitsin (rovamitsin)--makrolidnyi antibiotik dlia peroral'noi terapii vnebol'nichnykh pnevmonii.

Spiramycin activity against acute pneumonia has been studied in 21 outpatients (15 adults and 6 children). The drug was administered orally twice daily in a dose 3,000,000 units. The course lasted from 7 to 14 days. All the cases were confirmed roentgenologically. The disease ran a moderate-severity course. The response rate reached 95.2%. Another course of antibiotic therapy was not needed. Side effects were not registered. Bacteriological efficacy of spiramycin made up 71.3%. 14 out of 16 isolated strains of causative agents (S.pneumoniae, S.pyogenes, S.aureus, H.influenzae in 5, 1, 7 and 3 patients, respectively) proved sensitive to spiramycin. 2 patients developed mycoplasma infection diagnosed serologically. The findings confirm high therapeutic efficacy of spiramycin, its good tolerance. Spiramycin may be considered the drug of the priority choice in outpatient treatment of acute pneumonia.

[The neurohormonal characteristics of rats selected for the duration of the passive defense reaction and for the threshold of neuromuscular excitability]. / Neirogormonal'nye kharakteristiki krys, selektsionirovannykh po dlitel'nosti passivno-oboronitel'noi reaktsii i porogu nervno-myshechnoi vozbudimosti.

Two strains of rats, "genetic catalepsy" and "low-threshold", simulating some human psychopathological symptoms, were compared. Levels of brain monoamines and blood corticosterone and testosterone showed no common features in the strains studied. The levels of dopamine in amygdala and testosterone blood levels in rats of the two strains significantly deviated in opposite directions from corresponding controls. In "genetic catalepsy" strain noradrenaline content in striatum and diencephalon was decreased, and serotonin striatal level was increased.

[The general behavioral characteristics of rats selected for the duration of the passive defense reaction and for the threshold of neuromuscular excitability]. / Obshchie kharakteristiki povedeniia krys, selektsionirovannykh po dlitel'nosti passivno-oboronitel'noi reaktsii i porogu nervno-myshechnoi vozbudimosti.

Two strains of rats, (GC) ("genetic catalepsy"), and (Lt), ("low-threshold") proposed as models of human psychopathological symptoms, were compared. Characteristics of "activity" and "emotionality" in the open field were practically the same in the strains studied. Disturbance of motor plasticity seemed to be for the lack of circular movements in free behaviour. Injections of apomorphine induced oppositely directed effects on the number of yawns in GC and Lt rats. Galoperidol effect was cataleptogenic in both the strains. The similarity in open field behaviour parameters and the effects of apomorphine and galoperidol appeared to be underlain by a large number of common features in nervous system organization.