Mediator processes in the brain structures in the late periods after external and combined exposure to ionizing radiation

In experiments with mature Wistar male rats it was shown that X-radiation of 12.9 mCi/kg and the combined effect of X-rays and 131I of 6.5 mCi/kg changed the rate of mediator processes in the structures responsible for the hypothalamic function regulation. At remote times (6 months) following irradiation differences were observed in the discoordination of mediator interrelations associated with the peculiarities of the indirect effect of external and combined irradiation implemented via endocrine mechanism system.     

Rhythmic after-discharge in the cat cerebral cortex and deep brain structures during stimulation of the claustrum

Effects of stimulation of the claustrum and caudate nucleus in the neocortex and various deep brain structures were studied in acute experiments on unanesthetized cats immobilized with tubocurarine. A rhythmic after discharge appeared in neocortical areas 4–7 and 18 (according to Reinoso-Suarez' atlas), and also in the caudate nucleus and various parts of the thalamus. A similar discharge also was observed in the claustrum itself. Diencephalic brain section at the level of the ventral anterior nucleus weakened but did not completely abolish the cortical rhythmic after-discharge in the anterior regions of the neocortex evoked by stimulation of the claustrum. This discharge was completely blocked after sagittal brain section between the claustrum and the rest of the thalamus.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 15, No. 2, pp. 121–127, March–April, 1983.     

Paramembraneous microfilamentous structures of the synapses of rat cerebral cortex during sensitization by brain antigens

On the material contrasted by phosphotungstic acid the state of paramembranes microfilament structures of interneuronal contacts of molecular layer of sensomotor field cortex of rat brain of Krushynsky-Molodkina line during sensitization by homologous brain antigens was studied. Sharp reduction of general density of synapses and symmetric contacts because of damaging of paramembranes microfilament structures of cerebral cortex synapses and reduction of new contacts was proved that plays an essential role in changing of brain integrating activity during different pathological processes connected with autoimmune mechanism of neuronal tissue damaging.     

The intercentral relations of the frontal cortex and limbic structures of the brain in dogs]

In 3 dogs with implanted electrodes, in conditioned experiments correlation of the bioelectrical processes was studied by coherence function calculation of the hippocampus, hypothalamus, amygdala and frontal cortex biopotentials. It was shown, that the level of maximum values of coherence function of bioelectrical oscillations, led from various pairs of the studied brain structures significantly differed both in magnitude and frequency at which the greatest synchronization of biopotentials was noticed. In one dog with a high degree of connection between the hippocampus and hypothalamus biopotentials oscillations, a low synchronization of the frontal cortex and amygdala oscillations was found; in two other animals with a higher level of coherence between the oscillations of the frontal cortex and amygdala biopotentials, a lower degree of connection between the oscillations led from the hippocampus and hypothalamus was revealed. Synchronization of the biopotentials of the hippocampus and frontal cortex and also of the hippocampus and amygdala biopotentials proved to be low in all experimental dogs, what additionally testifies to different role of these structures in organization of the behaviour.     

Indices of RNA metabolism in the brain stem of rats under superlethal exposure to ionizing radiation

A study was made of the content of hnRNA, nuclear poly(A) RNA and biosynthesis of rlnRNA in truncus cerebri of rats divided into 3 groups by the forced swimming test 6-8 min and 60 min after a short-term exposure to sparsely ionizing radiation of 100 Gy. The observed changes in the nuclear RNA metabolism can subsequently lead to the impairment of the synthesis of proteins required for normal functioning of CNS, and to the development of CNS syndrome.     

Persistence of hyperbaric oxygen-induced oxidative effects after exposure in rat brain cortex tissue

Hyperbaric oxygen (HBO) causes oxidative stress in several organs and tissues. Due to its high rate of blood flow and oxygen consumption, the brain is one of the most sensitive organs to this effect. Many studies have reported oxidative effects of HBO, but there is no comprehensive data about how long this effect persists. The aim of this study was to elucidate the duration of HBO-induced oxidative/antioxidant action. Male Sprague-Dawley rats were divided into 5 groups. Except for the controls, the animals were subjected to 100% oxygen for 2 h at 3 atm and differed from each other by the time to dissection after exposure that began at 30, 60, 90, or 120 min. Thiobarbituric acid-reactive substances (TBARS), as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity was determined in brain cortex tissue. Additionally, nitrite-nitrate (NO(x)) concentrations were measured. All measured parameters were found to be significantly increased 30 min after exposure. SOD and GSH-Px levels persisted at significantly high levels for 60 min. In conclusion, the oxidative effect of HBO was shown to persist only for 1 h. Further studies should be performed to elucidate the possible molecular interactions during this period.     

Early gene expression profile in mouse brain after exposure to ionizing radiation

Acute changes in the gene expression profile in mouse brain after exposure to ionizing radiation were studied using microarray analysis. RNA was isolated at 0.25, 1, 5 and 24 h after exposure to 20 Gy and at 5 h after exposure of the whole brain of adult mice to 2 or 10 Gy. RNA was hybridized onto 15K cDNA microarrays, and data were analyzed using GeneSpring and Significant Analysis of Microarray. Radiation modulated the expression of 128, 334, 325 and 155 genes and ESTs at 0.25, 1, 5 and 24 h after 20 Gy and 60 and 168 at 5 h after 2 and 10 Gy, respectively. The expression profiles showed dose- and time-dependent changes in both expression levels and numbers of differentially modulated genes and ESTs. Seventy-eight genes were modulated at two or more times. Differentially modulated genes were associated with 12 different classes of molecular function and 24 different biological pathways and showed time- and dose-dependent changes. The change in expression of four genes (Jak3, Dffb, Nsep1 and Terf1) after irradiation was validated using quantitative real-time PCR. Up-regulation of Jak3 was observed in another mouse strain. In mouse brain, there was an increase of Jak3 immunoreactivity after irradiation. In conclusion, changes in the gene profile in the brain after irradiation are complex and are dependent on time and dose, and genes with diverse functions and pathways are modulated.     

MiR-21 is continually elevated long-term in the brain after exposure to ionizing radiation

Ionizing radiation stimulates miR-21 expression in different types of mammalian cells in culture. However, it remains unclear whether radiation could stimulate miR-21 expression in brain cells and tissue and, if so, how long the upregulation of miR-21 would be maintained after exposure to different types of radiation. To answer these questions, we examined the miR-21 levels in irradiated mouse hippocampal cells and brain tissue from mice at different times up to 1 year after whole-body exposure to 0.5 Gy of X rays [low linear energy transfer (LET)] or (56)Fe ions (high LET). The results showed that radiation stimulated miR-21 expression in mouse hippocampal cells and upregulation of EGFR, which is similar to that in human hepatocytes, as we reported previously. Interestingly, the miR-21 levels gradually increased within 1 year after irradiation, although there was no significant difference in the miR-21 low- and high-LET irradiated mice. The high expression of miR-21 in the brain was also associated with high expression of EGFR in irradiated mice; thus our data strongly support that EGFR and miR-21 are in a positive regulatory loop, because it is known that radiation stimulates miR-21 through the EGFR/Stat3 pathway and miR-21 activates the EGFR pathway. Since the brain is relatively resistant to radiation-induced histomorphological changes, our findings may provide a new way to explore radiation-induced pathological changes in the brain by investigating miR-21 and its multiple targets.     

Cytochemistry and morphology of synaptic structures in the cerebral cortex of rat

Summary Glycogen synthetase and phosphorylase activities in the paraboloid glycogen of the accessory cone of the chick retina were studied electron histochemically, while the paraboloid glycogen was observed by electron microscopy.Some of the paraboloid of the accessory cone of the chick retina contained abundant glycogen granules, but some showed no glycogen granules. Some inner segments of the accessory cones were occupied by deposition of glycogen granules.Polyglucose particles synthesized by glycogen synthetase activity in the chick paraboloid were demonstrated in fine granular form with diameter from 70 to 130 Å. These particles were less stainable with lead citrate than native glycogen granules. Synthesized polyglucose particles were located in the cytoplasmic matrices and expanded them. Lamellar and membrane structures were not related to synthesized polyglucose.Polyglucose particles synthesized by phosphorylase activity in the chick paraboloid were located in the cytoplasmic matrices and expanded them widely. Tubular structure appeared to be flattened by deposition of synthesized polyglucose particles. These features showed the resemblance to the inner segment of the accessory cone filled with a great amount of glycogen granules. Synthesized polyglucose was demonstrated in macromolecular form with diameter from 200 to 500 Å. There were no relationships between lamellar or membrane structures and polyglucose.The present study suggests that the chick paraboloid not only is a field for active glycogen metabolism, but also becomes a storage of glycogen.     

Down-regulation of 3H-imipramine binding sites in rat cerebral cortex after prenatal exposure to antidepressants

Several antidepressant drugs were given to pregnant rats in the last 15 days of gestation and 3H-imipramine binding (3H-IMI) was subsequently measured in the cerebral cortex of the offspring. The selective serotonin (5-HT) uptake blockers chlorimipramine and fluoxetine as well as the selective monoamine oxidase (MAO) inhibitors clorgyline and deprenyl induced, after prenatal exposure, a down-regulation of 3H-IMI binding sites at postnatal day 25. The density of these binding sites was still reduced at postnatal day 90 in rats exposed in utero to the MAO inhibitors. The antidepressants desipramine and nomifensine were ineffective in this respect. After chronic treatment of adult animals, only chlorimipramine was able to down-regulate the 3H-IMI binding sites. Consequently, prenatal exposure of rats to different antidepressant drugs affecting predominantly the 5-HT systems induces more marked and long-lasting effects on cortical 3H-IMI binding sites. The results suggest that the developing brain is more susceptible to the actions of antidepressants.     

Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats

The purpose of this study was to investigate the role of central 5-HT_2C receptor binding in rat model of pancreatic regeneration using 60–70% pancreatectomy. The 5-HT and 5-HT_2C receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [³H] mesulergine in cerebral cortex showed a significant decrease (p < 0.05) in maximal binding (B_max) without any change in K_d in 72 h pancreatectomised rats compared with sham. The decreased B_max reversed to sham level by 7 days after pancreatectomy. In brain stem, Scatchard analysis showed a significant decrease (p < 0.01) in B_max with a significant increase (p < 0.01) in K_d. Competition analysis in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after pancreatectomy. Thus the results suggest that 5-HT through the 5-HT_2C receptor in the brain has a functional regulatory role in the pancreatic regeneration.     

Canges in the monoamine content in the cat brain in a unilateral lesion of the cerebral cortex]

A spectrofluorometric study of the changes in serotonin and noradrenalin content was carried out in the cortex of large hemispheres, the hypothalamus and the midbrain on the 5th-6th day after creation of a pathological focus in the area of the occipital portion of the cortex in 12 cats. Diffuse changes in the bioelectrical activity of the brain were revealed on the EEG at this period: there appeared peak-like variations and slow waves of increased amplitude. There was noted a marked decrease in serotonin content in the cortex of the large hemispheres with the prevalance of an effect in the area directly adhering to the focus of affection. A tendency to reduction in serotonin level was revealed in the hypothalamus and the midbrain. The content of noradrenalin in the mentioned structures of the brain showed no significant change. The significance of the serotoninergic structures of the brain in the mechanisms participating in the restoration of the functional condition of the brain after its experimental injury is discussed.