[Current aspects of the search of effective nootropic drugs]. / Sovremennye aspekty poiska éffektivnykh nootropnykh sredstv.

The authors review different mechanisms of mnemotropic and cerebroprotective effects of nootropic drugs. The data concerning the molecular mechanisms of action of the structural analogs of the memory stimulant ethylnorantifeine (etimizol) have been summarized and analyzed. It is shown that the effects of antifeines on the retention of the conditioned reflexes are independent of their effects on the cAMP system and structural-functional condition of the neuronal membrane. The key role in the action of these compounds on the long-term memory is played by the activity of the genetic apparatus. The existence of nootropic receptors in neuronal chromatin is assumed.

[The participation of RNA synthesis in the process of the acquisition and retention of conditioned reflexes (a study using antifeins)]. / Uchastie sinteza RNK v protsesse vyrabotki i sokhraneniia uslovnykh refleksov (issledovanie s ispol'zovaniem antifeinov).

RNA-synthesizing activity of neuronal nuclei in the neocortex of rats increases after the termination of conditioning depending on the degree of learning. RNA synthesis shifts induced by propylnorantifein and the demethylated derivatives of ethylnorantifein are correlated only with the influence of the drugs on the retention but not the learning. Participation of RNA synthesis by the neurons of the neocortex in the mechanisms of long-term memory is discussed.

[Skeletal muscle nuclear ATPase under denervation]. / ATP-azy iader skeletnykh myshts pri denervatsii.

Denervation of the rabbit gastrocnemius muscle is shown to result after 18 and 72 h in a decrease of Mg2+-, Ca2+-dependent and an increase of Mg+-dependent parts of nuclear ATPase activity, with the total level of the enzyme activity retained. 7 days later the total ATPase activity of nuclei decreases as well as the expense of its EGTA-dependent part. These changes correlate with those in the nuclear Ca total content. Indirect electrostimulation of the denervated muscle increase both the 7g2+-, Ca2+-dependent ATPase activity and the Ca content in nuclei. Tenotomy for 18 h does not change these parameters.

[Comparison of superslow activity with changes in the function of the neocortical cytostructures]. / Sopostavlenie sverkhmedlennoi aktivnosti s izmeneniiami funktsional'nogo sostoianiia tsitostruktur neokorteksa.

Effects of ethimizole on the infraslow ascillations of the brain electrical activity were correlated with the pattern of its distribution within cellular structures. A negative wave of the infraslow activity was found to occur after the drug administration at the moment of its maximal inclusion into the two cellular fractions: the nuclei and the surface proteins of the endoplasmatic net. These structures seem to play part in changes of the central nervous system's functional state.

[Surface membrane proteins of endoplasmic reticulum in brain and liver cells]. / Poverkhnostnye belki membran endoplazmaticheskoi seti kletok pecheni i mozga

A comparative study of proteins adsorbed on outer surface of microsomal membranes was carried out. Electrophoretic differences between endoplasmic reticulum proteins from liver and brain cells were revealed. These differences were not observed in the presence of sodium dodecyl sulphate. Proteins of brain microsomes are shown to bind in vitro with membranes of brain endoplasmic reticulum to a higher extent than with liver microsomal membranes.

[Participation of protein synthesis in brain cell structures in the action of antifeins on long-term memory]. / Uchastie sinteza belkov tsitostruktur golovnogo mozga v deistvii antifeinov na dolgovremennuiu pamiat'.

Incorporation of 3H-leucine into proteins of rat brain cell structures during application of antifeins (compounds of alternative action on memory processes) has been studied. No correlation was observed between changes in protein synthesis in nuclei, mitochondria, components of endoplasmic reticulum and memory effects of ethyl-, allyl- and propylnorantifeins. Only M1 and M2-demethylated structural analogs of ethylnorantifeins (exerting the most effective action on RNA synthesis and retention of conditional reflexes) enhanced the synaptosomal protein synthesis.

[Effects of antifeins with different memory effects on cAMP phosphodiesterase, lipid peroxidation and RNA synthesis in rat brain neurons]. / Vliianie antifeinov s razlichnymi mnesticheskimi éffektami na fosfodiésterazy tsAMF, perekisnoe okislenie lipidov i sintez RNK v neironakh golovnogo mozga krys.

It has been shown that ethylnorantifein and its structural analogues with opposite effects on long term memory reduce the activity of membrane bound phosphodiesterase cAMP with high and low affinity and exert the same directed influence on lipids peroxidation in membranes. A positive correlation was observed only between the action of these substances on the long term memory and their influence on the RNA synthesis in the rat brain nuclei. Ethylnorantifein and its demethylated analogues increased RNA synthesizing activity while allyl- and propylnorantifeins decreased it. The molecular mechanisms of memory effects of neuroactive substances are discussed.

[Effect of a single ethanol administration on the behavior and the RNA-synthesizing activity of the cell nuclei of the cerebral cortex of the rat]. / Vliianie odnokratnogo vvedeniia étanola na povedenie i RNK-sinteziruiushchuiu aktivnost' kletochnykh iader kory mozga krys.

A single intraperitoneal injection of ethanol (2 g/kg) disturbed the learning and performance of one trial passive avoidance task and decreased (by 14 %) the level of RNA-synthesizing activity of brain cortical synaptosomes in rats. The data obtained are discussed in accordance with the hypothesis that ethanol affects synaptic transmission in the central nervous system.

[ATPase activity and ATP-dependent accumulation of Ca2+ in skeletal muscle nuclei. Effects of denervation and electric stimulation]. / Issledovanie ATPaznoi aktivnosti i ATP-zavisimoi akkumuliatsii Ca2+ iadrami skeletnykh myshts. Effekty denervatsii i élektricheskoi stimuliatsii.

The dependence of the ATPase activity of skeletal muscle nuclei on divalent cations was studied. An addition of Ca2+ significantly increased the activity of nuclear ATPase. Mg2+ exerted an activating effect in the presence of 10(-5) M Ca2+ and an inhibiting effect in the presence of 2 x 10(-3) M Ca2+. Predominant localization of Ca-ATPase in the nucleoli and in the internal nuclear envelope was demonstrated by an electron microscopic histochemical technique. ATP increased the uptake of 45Ca by muscle nuclei; the optimal conditions for this incorporation were established. The changes in Ca-ATPase activities and in the ATP-dependent uptake of 45Ca induced by denervation and electric stimulation were found to be synchronous and unidirectional.

[Effect of HMG proteins and their phosphorylated forms on the process of transcription in neuronal nuclei of the rat brain (data from an immunochemical analysis)]. / Vliianie belkov HMG i ikh fosforilirovannykh form na protsess transkriptsii i neironal'nykh iadrakh golovnogo mozga krys (dannye immunokhimicheskogo analiza)

It was found that chromatin transcription in the neuronal nucleus of rat brain is inhibited by antisera to proteins HMG 14, HMG 17 and HMG 2. It is known that chromatin transcription of the neuronal nucleus and phosphorylation of chromosomal proteins are activated by etimizol. The phosphorylation of chromosomal proteins activated by etimizol is inhibited by the antiserum to HMG 14 (but not to HMG 17). The data obtained are suggestive of a possible role of HMG proteins and their phosphorylated forms in the regulation of transcription.

[Dynamics of the distribution of labeled etimizol in brain cell structures]. / Dinamika raspredeleniia mechenogo étimizola v tsitostrukturakh golovnogo mozga.

The time course of 14C-etimizol distribution in cell structures of the rat cerebral cortex was studied. Two minutes after intraperitoneal injection etimizol penetrates brain cells. At this time the greater portion of the drug is found in cytosol. In five minutes the maximal part of the label gets bound with cell nuclei and microsomal protein fraction extracted with 0.14 M NaCl. These two cell fractions show the highest radioactivity throughout the entire observation period (up to 7 days). Since these fractions are reported to be capable of calcium accumulation, a suggestion is made that metabolic effects of etimizol are likely to be related to calcium metabolism.

[Role of calcium in realization of nervous control during RNA synthesis in skeletal muscles]. / Rol'kal'tsiia v realizatsii nervnogo kontrolia sinteza RNK b skeletnykh myshtsakh.

The effects of Ca2+ on the RNA polymerase activity of the nuclei isolated from normal and denervated gastrocnemius muscles of the rabbit were studied. It was shown that 18 hrs after denervation the RNA synthesis in vitro, Ca2+ content and the Ca, Mg-ATPase activity of the nuclei are decreased. After addition of exogenous Ca2+ the incorporation of labelled UTP into the nuclei is stimulated in the denervated muscle and is inhibited in the control. Electrostimulation of the denervated muscle at the peripheral part of the sciatic nerve for 3 hrs increases both the RNA synthesis in the nuclei and the Ca2+ content, as well as the Ca, Mg-ATPase activity. Exogenous Ca2+ has an inhibitory effect on the nuclei of the stimulated muscle. The correlation established is indicative of participation of Ca2+ in the transmission of excitation in skeletal muscle sarcolemma to the processes occurring in nuclear structures.