The effects of the neurotoxin kainic acid on a food-producing habit were studied in Wistar rats in an experimental chamber. Single doses of kainic acid at a subconvulsive dose (8 mg/kg, i.p.) were found to impair the habit, onset of impairment being delayed by several weeks rather than immediate. Conversely, administration of the neurotoxin at the convulsive dose (10 mg/kg) impaired reproduction of the habit with onset within several hours after treatment and persistence for periods of up to 10 days, though this dose did not prevent the acquisition of a new food-procuring habit. These defects in the reproduction of long-term memory traces were explained in terms of the characteristics of the effects of kainic acid on the hippocampal system, which is the most susceptible to systemic administration of the neurotoxin.
Lipid composition of homogenate and neuronal and glial nuclei of the brain cortex of Wistar rats was studied under normal conditions and after seizures induced by injection of picrotoxin. Seizures increased contents of lysophosphatidylcholine, sphingomyelin, and total phospholipids in the homogenate. In neuronal nuclei contents of total phospholipids, sphingomyelin, phosphatidylcholine, and phosphatidylserine decreased, and contents of free fatty acids and lysophosphatidylcholine increased. In glial nuclei content of total phospholipids decreased and content of free fatty acids increased. The role of changes in the lipid composition of the neocortex cells during seizures and the involvement of lipid messengers in signal mechanisms are discussed.
Effect of the neurotoxin kainic acid to the food-procuring task were studied in Wistar rats. A single injection of the acid in subconvulsive dose (8 mg/kg) impaired the task performance within some weeks but not immediately after the treatment. Higher doses of kainic acid (10 mg/kg) impaired the task performance within a few hours after treatment for up to 10 days. The treatment did not prevent rat's learning of a new task in the same experimental chamber. The revealed deficit in the long-term memory retrieval might be explained by specific effects of kainic acid upon the hippocampal system.
Experiments on resting hepatocytes with inactive c-fos gene and active albumin gene. We revealed that DNA of the transcribed gene is less susceptible to the influence of endogenous Ca2+/Mg2+-dependent DNases in matrix-associated and highly soluble chromatin fractions. In the fraction of low soluble chromatin active gene was more accessible for DNases. Our results indicate that activity of endogenous DNases can change in the transcribed gene locus.
Accumulation of c-fos gene locus DNA In the nuclear matrix of hepatocyte nuclei was observed during induction of c-fos with cycloheximide. No enhanced association with the nuclear matrix was detected for inactive immunoglobulin gene locus. The use of endogenous DNases allows isolation of nuclear matrix preparations enriched with transcribing chromatin.
The degree of nucleolysis is of critical significance for isolation of nuclear matrix (NM) specifically enriched in transcribed DNA sequences, as demonstrated using an example of inactive (c-fos, c-myc, andCκ) and active (p53, albumin, and28S rRNA) genes in resting hepatocytes. The optimal degree of nucleolysis is characterized by degradation of loop domains of chromatin, with the relatively uniform molecular weight distribution of DNA being preserved. Deviation from these parameters leads to nonspecific fragmentation of chromatin in various gene loci and isolation of NM samples nonspecifically enriched with or depleted of transcribed DNA sequences. Under optimal hydrolytic conditions, the transcribed chromatin is more resistant to endogenous DNase attack, which allows selective conservation of its association with the nuclear matrix
Wistar rats were trained food-procuring task for 5 days and then extinction of the operant behavior was studied for 6 days after injection of an epileptogen (kainic acid, 8 mg/kg, intraperitoneally). Kainic acid induced long-term impairment of inhibitory processes in the brain, which impeded extinction of a conditioned response. This effect was prevented by daily injections of anticonvulsant sodium valproate (300 mg/kg for 4 days).
In the monolayer of rat hepatocytes in vitro, the circadian rhythms were revealed of 3H-leucine incorporation in proteins and in aminoacyl-tRNA(Leu) fraction. The oscillations were mainly synphasic, though coordination between aminoacylation and protein synthesis was not stable in the coarse of time. In cell free system with the excess of ATP and aa-tRNA, the rhythm of 3H-leucine incorporation was also clear. This means, that oscillatory kinetics of the protein synthesis rate is not caused by oscillation of ATP which has been revealed earlier in the hepatocyte monolayer.
The changes in the structure and RNA-polymerase activity of rat liver cell chromatin after a single injection of cycloheximide (3 mg/kg of body mass) were studied. The cycloheximide-induced fluctuations in protein synthesis rates are concomitant with episodes of drastic changes in the chromatin structure. The reorganization of the general protein structure is associated with an increase or a decrease of the RNA-polymerase II activity. The data obtained suggest that the activation-inactivation of RNA-polymerase II in cell nuclei is due to reorganization of chromatin infrastructures--from higher levels of the electron-dense chromatin package to the unfolded nucleosomes of the transcriptionally active protein.