ABSTRACT
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.
Subject(s)
Conditioning, Classical/drug effects , Etimizol/analogs & derivatives , Imidazoles/pharmacology , RNA/drug effects , Animals , Avoidance Learning/drug effects , Avoidance Learning/physiology , Cell Nucleus/drug effects , Cell Nucleus/physiology , Cerebral Cortex/drug effects , Cerebral Cortex/physiology , Conditioning, Classical/physiology , Etimizol/pharmacology , Feeding Behavior/drug effects , Feeding Behavior/physiology , Male , Memory/drug effects , Memory/physiology , Neurons/drug effects , Neurons/physiology , RNA/biosynthesis , RatsABSTRACT
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.
Subject(s)
Brain/metabolism , Imidazoles/pharmacology , Memory/drug effects , Nerve Tissue Proteins/biosynthesis , Animals , Brain/drug effects , Brain/ultrastructure , Cell Nucleus/metabolism , Endoplasmic Reticulum/metabolism , Male , Mitochondria/metabolism , Rats , Synaptosomes/drug effects , Synaptosomes/metabolismABSTRACT
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.
Subject(s)
Brain/cytology , Cell Nucleus/metabolism , High Mobility Group Proteins/metabolism , Neurons/metabolism , Transcription, Genetic , Animals , Brain/metabolism , Cattle , Electrophoresis, Polyacrylamide Gel , Etimizol/pharmacology , Immune Sera , Immunohistochemistry , Phosphorylation/drug effects , RatsABSTRACT
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.
Subject(s)
Psychotropic Drugs , Animals , Brain/drug effects , Brain/metabolism , Cerebral Cortex/drug effects , Cyclic AMP/metabolism , Etimizol/pharmacology , Humans , In Vitro Techniques , Memory/drug effects , Neurons/drug effects , RNA/biosynthesis , RNA/drug effects , RatsABSTRACT
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.
Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/analysis , Brain/metabolism , Etimizol/pharmacology , Lipid Peroxidation/drug effects , Memory/drug effects , RNA/biosynthesis , Animals , Brain/drug effects , Brain/enzymology , Etimizol/analogs & derivatives , In Vitro Techniques , Male , RatsSubject(s)
Brain/drug effects , Chromatin/drug effects , Etimizol/pharmacology , Imidazoles/pharmacology , Memory/drug effects , Animals , Brain/metabolism , Calcium-Transporting ATPases/metabolism , Chromatin/metabolism , Dose-Response Relationship, Drug , Male , RNA/biosynthesis , Rats , Stimulation, ChemicalABSTRACT
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.
Subject(s)
Behavior, Animal/drug effects , Cell Nucleus/drug effects , Cerebral Cortex/drug effects , Ethanol/administration & dosage , RNA/biosynthesis , Animals , Cell Nucleus/metabolism , Cerebral Cortex/metabolism , Conditioning, Classical/drug effects , Dose-Response Relationship, Drug , Male , Memory/drug effects , RatsABSTRACT
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.
Subject(s)
Cerebral Cortex/physiology , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/ultrastructure , Etimizol/metabolism , Etimizol/pharmacology , Male , Rats , Rats, Inbred Strains , Subcellular Fractions/metabolism , Time FactorsABSTRACT
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.
Subject(s)
Cerebral Cortex/metabolism , Etimizol/metabolism , Imidazoles/metabolism , Animals , Carbon Radioisotopes , Cell Nucleus/metabolism , Etimizol/administration & dosage , Injections, Intraperitoneal , Male , Rats , Rats, Inbred Strains , Subcellular Fractions/metabolism , Time FactorsABSTRACT
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.
Subject(s)
Adenosine Triphosphatases/metabolism , Calcium-Transporting ATPases/metabolism , Calcium/metabolism , Cell Nucleus/enzymology , Muscle Denervation , Muscles/physiology , Animals , Biological Transport, Active , Cell Nucleolus/enzymology , Cell Nucleus/ultrastructure , Electric Stimulation , Enzyme Activation , Magnesium/pharmacology , Male , Microscopy, Electron , Muscles/enzymology , RabbitsABSTRACT
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.
Subject(s)
Adenosine Triphosphatases/metabolism , Muscle Denervation , Muscles/enzymology , Animals , Calcium/pharmacology , Magnesium/pharmacology , Male , RabbitsABSTRACT
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.
Subject(s)
Calcium/pharmacology , Cell Nucleus/enzymology , DNA-Directed RNA Polymerases/metabolism , Muscle Denervation , Muscles/enzymology , RNA/biosynthesis , Animals , Calcium-Transporting ATPases/metabolism , Cell Nucleus/drug effects , Electric Stimulation , Magnesium/pharmacology , Muscles/physiology , Rabbits , Sciatic Nerve/physiologyABSTRACT
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.