The action of antifeins with different memory effects on the cAMP-independent protein kinases of brain chromatin]

The two cAMP-independent protein kinases (PK I and PK II) were obtained from neuronal chromatin of rat brain. Nonhistone HMG-proteins were used as phosphorylation substrates. The possibility of antifeines direct action on PK II was revealed. Ethylnorantifeine and its demethylated analogues increased enzyme activity whereas allylnorantifeine decreased it. The action of ethylnorantifeine and its structural analogues were similar to its influence on neuronal RNA-synthesizing activity and long-term memory. The conclusion was made that cAMP-independent PK II may be the target of antifeines action during realization of its mnestic effects.     

Effects of antifeins with different memory effects on cAMP phosphodiesterase, lipid peroxidation and RNA synthesis in rat brain neurons]

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.     

Autoradiography of protein synthesis as a method of assessment of morphofunctional changes in brain structures]

A combination of two groups of autoradiography technique (for a hole brain and individual cells) was applied with using 3H-leucine to evaluate the changes of brain functional activity on the level as anatomical structures and as different type neurons. It was found that Wistar rats with lowered motor activity induced by 3-4 weeks treatment with L-DOPA 100 mg/kg displayed the motor nuclei of the brain stem the cerebellum as highly labelled structures and the motor cortex and n. caudatus as feebly ones in comparison with control. However, a quantitative assessment of silver grains over the neurons of layers III and V of motor cortex and n. caudatus showed not only a significant increase of labelling, especially in neurons of layer V on 174%, in comparison with control but revealed unequal labelling of different type neurons. It was concluded that the applied two groups of autoradiography technique can be a useful approach to assess the brain functional activity.     

Participation of the adenylate cyclase system in inductive synthesis of acetylcholinesterase in the brain]

The enhancement of the brain acetyl cholinesterase (ACHE) activity in rats by the intraventricular injection of adrenaline or dibutiryl analogue cyclic adenosine-3',5'-monophosphate (cAMP) was shown to be due to the enzyme inductive synthesis. ACHE induction manifests itself more in the subcortical white matter than in the cortex. The stimulating effect of adrenaline on the ACHE activity is suppressed under the beta-adrenoreceptor block, while the cAMP effect remains unchanged. On the contrary, the block of the alpha-adrenoreceptors stimulates the enzyme synthesis induction. The effects of adrenaline and cAMP are of the same direction and are realized through the beta-adrenoreceptors. The enhancement of ACHE activity during the block of the alpha-adrenoreceptors is accounted for by the elimination of their inhibitory influence on the beta-adrenoreceptors.     

Participation of mesencephalic structures in vocal reactions]

Electrical stimulation and ablation of the midbrain structures in hens and one-day old chickens have revealed the structures (ICO, MLD, MLV, IPC and IMC) involved in the formation of vocal reactions. The paper outlines the functional characteristics of the structures and their dissimilarities which are determined by the type of their units. In the course of individual development of the hens, there is an increase of excitability and lability of the nervous processes in the examined structures.     

The effect of protein synthesis inhibition in the central nervous system on long-term memory formation in some behavioral tasks

The effect of the maximum protein synthesis inhibition in brain and spinal cord on long-term memory formation in extreme situations was studied in various new behavioral tasks in rats. Cycloheximide injected bilaterally into the lateral ventricles three hours before learning suppressed protein synthesis in the central nervous system by 96% during one hour after learning. Forty-four hours after learning in a standard Morris water maze, the information about the platform position was not retained, whereas no memory disorder was observed in case of learning in a simplified Morris maze or a new test learned jump-out-of-water task. A more prolonged suppression of protein synthesis (76%, ten hours after learning) elicited amnesia in five out of eight rats learned in a simplified Morris maze but not disturbed information storage after 48 h and 14 days in the learned jump-out-of-water task. It was concluded that protein synthesis inhibitors are not a universal tool for disrupting formation of long-term memory. It was assumed that under extreme conditions, sometimes procedural long-term (to two weeks) memory is formed without de novo protein synthesis.     

Participation of suppressor cells in the depressing action of serotonin on immunogenesis]

The transfer of 20 x 10(6) T and B cells of lymphoid organs from the donors immunized with sheep erythrocytes and having elevated serotonin level to the recipients immunized with SRBC decreased the intensity of immune response (rosette formation and direct plaque formation). The elevation of serotonin level in the donors induced the appearance of T and B suppressors in the thymus and the bone marrow respectively and increased the population of T and B suppressors in the spleen and, to a lesser extent, in lymph nodes.     

The mechanisms of memory reorganization during the retrieval of acquired behavioral experience in chicks: the effects of protein synthesis blockade in the brain]

It is currently assumed that disruption of memory formation by inhibitors of protein synthesis can occur in a relatively short time interval before and after training. However, there is some evidence that memory may be disrupted by delayed injections of protein synthesis inhibitors during "reminder" treatment, i.e., environmental cue that was presented earlier during the training procedure. Our experiments were conducted to test the late effects of protein synthesis inhibitor cycloheximide on memory in chicks using a reminder treatment. A standard passive avoidance task was presented to day-old chicks. A reminder (a dry bead of the same color as during training) was delivered within 2, 24, or 48 hours after the training. Chicks were bilaterally intracranially injected with cycloheximide (20 micrograms) into the IMHV area 5 min prior to reminder administration. Testing was conducted 0.5, 1, 3, 24, and 48 hours after the reminder. Administration of cycloheximide before the reminder resulted in transient amnesia. Duration of amnesia decreased with increasing interval between the training and reminder procedures. These results suggest that memory reactivated by the reminder treatment is subjected to reorganization and reconsolidation depending on protein synthesis. The gradual decrease in vulnerability of memory to protein synthesis inhibitor points to development of memory consolidation process in the interval between 2 and 48 h after training.     

Changes in the protein composition of the synaptic structures of the brain of rats in tetanus intoxication]

As shown by the method of electrophoresis on polyacrylamide gel, the number of proteins with low electrophoretic mobility proved to be increased in the triton extract fractions of synaptic structures isolated from spinal cord of rats with local tetanus; no changes in the protein spectrum were revealed in the dodecyl-sulphate extract. In vitro tetanus toxin stimulated the lysin-H3 incorporation into the total proteins of synaptosomes of rat brain cortex.     

Imitation of neurophysiological effects of long-term sensitization with the action of the blockers of protein synthesis in snailsHelix lucorum

The experiments on command neurons of defensive behavior in snailsHelix lucorum have shown that the synaptic components of responses to the testing stimuli are facilitated within 65 to 75 min after the onset of the application of the protein synthesis inhibitors cycloheximide or anisomycin (30 µM during 30 min) to the central nervous system. At the same time, the parameters of the electrical properties of neuronal membrane (membrane potential level and excitability) were not affected by the blockers. The facilitatory effects were not observed when the blockers were applied for a longer period or when their concentration was raised to 300 µM. The blockade of the responses to different sensory stimuli appeared selective. The facilitation of the responses to tactile stimulation of the head, to weak quinine solution, and to carrot juice lasted for about an hour, 2–3 h and about 1.5 h, respectively. The blockers facilitated only the responses to tactile stimulation of the head, but did not change the responses to stimulation of the middle part of the foot or the mantle bolster. Some characteristics of the blocking effects are similar to those of long-term sensitization. The blocking effects observed are suggested to be due to activation of synthesis of short-living proteins functionally related, in particular, to selective regulation of synaptic transmission.Neirofiziologiya/Neurophysiology, Vol. 26, No. 1. pp. 61–67, January–February, 1994.     

Effect of protein synthesis inhibitors on DNA replication. I. Effect of the short-term action of cycloheximide on cell permeability for thymidine in vitro]

The effect of protein synthesis inhibitors on DNA replication was studied on L cells. After a 10 minutes' action of the inhibitors, protein synthesis was seen to be completely blocked, and DNA synthesis decreased by 85%. Four hours after a 20-minutes' cycloheximide treatment, the cells completely restored their ability to protein synthesis and DNA replication and even surpass the control level, due, probably, to a partial cell synchronization in S period. The short action of cycloheximide did not interfere with thymidine uptake by the cells. The rate of the exogenous precursor uptake was even higher than that in the control, apparently, because of its much reduced utilization in the inhibited DNA synthesis.     

Effects of long-term action of direct electric field on brain slices

An attempt of modeling of experimental paradigm of long-term transcranial direct current stimulation (ltDCS) ofa human brain by constant electric field was undertaken on rat hippocampal slices. At anodal or cathodal direction of electric field (14 min, 250 mV/mm) statistically significant changes of population spikes (pop-spikes) amplitude in the field CAl towards increase or decrease respectively occurred in reply to stimulation of Schaffer collaterals (1/30). Long-lasting aftereffects were not observed. NMDA receptors blockade by MK-801 removed field-generated effects and caused the gradual j reduction of pon-spikes throughout all time of registration. The assumption is come out that the phenomenon of reduction of pop-spikes can reflect synaptic transforming in a "silent" condition.     

Effect of phenylalanine on protein synthesis in the developing rat brain

1. Inhibition of the rate of incorporation of [(35)S]methionine into protein by phenylalanine was more effective in 18-day-old than in 8-day-old or adult rat brain. 2. Among the subcellular fractions incorporation of [(35)S]methionine into myelin proteins was most inhibited in 18-day-old rat brain. 3. Transport of [(35)S]methionine and [(14)C]leucine into the brain acid-soluble pool was significantly decreased in 18-day-old rats by phenylalanine (2mg/g body wt.). The decrease of the two amino acids in the acid-soluble pool equalled the inhibition of their rate of incorporation into the protein. 4. Under identical conditions, entry of [(14)C]glycine into the brain acid-soluble pool and incorporation into protein and uptake of [(14)C]acetate into lipid was not affected by phenylalanine. 5. It is proposed that decreased myelin synthesis seen in hyperphenylalaninaemia or phenylketonuria may be due to alteration of the free amino acid pool in the brain during the vulnerable period of brain development. Amyelination may be one of many causes of mental retardation seen in phenylketonuria.