scholarly journals The time course of changes in the state of monoaminergic systems in the brain of mice under the acute hypoxia with hypercapnia

2019 ◽  
Vol 65 (6) ◽  
pp. 485-497
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
N.A. Kuritcyna ◽  
E.R. Bychkov ◽  
...  

In socially isolated male outbred albino mice, the changes of monoaminergic systems under acute hypoxia with hypercapnia were studied. In cerebral cortex, hippocampus and striatum of the right and left sides of the brain, the concentrations of norepinephrine, dopamine, serotonin and their metabolites – dihydroxyphenylacetic, homovanillic and 5-hydroxyindoleacetic acids were investigated using the HPLC method. In isolated mice, which were not subjected to hypoxia with hypercapnia, higher levels of dopamine and serotonin in the left cortex were found. There was no asymmetry in monoamines and their metabolites in other studied brain structures. 10 min after the onset of exposure, acute hypoxia with hypercapnia resulted in a right-sided increase in norepinephrine levels and a decrease in dopamine levels in the striatum and serotonin levels in the hippocampus. In the cerebral cortex, 10 min after of hypoxic exposure beginning, there was a left-sided decrease in the dopamine content, while the original asymmetry found in the cortex of intact animals disappeared. In isolated mice perished of hypoxia with hypercapnia, almost all parameters returned to the control level. The exception was the ratio of serotonin metabolite level to the neurotransmitter, which in the right cortex became lower than in control animals. In white outbred mice, the brain monoaminergic systems are suggested to be relatively resistant to the negative consequences of hypoxia and hypercapnia, and corresponding shifts resulting in the reflex brain response to changes in the gas composition of the respiratory air.

2018 ◽  
Vol 64 (6) ◽  
pp. 511-516 ◽  
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
N.A. Kuritcyna ◽  
E.R. Bychkov ◽  
...  

The experiments were performed in male albino outbred mice kept in a group and under the conditions of long-term social isolation. The changes in the monoaminergic systems of the left and right hemispheres of the brain after acute hypoxia with hypercapnia have been studied. The levels of dopamine (DA), serotonin (5-HT) and their metabolites – dioxyphenylacetic (DOPAC), homovanillic (HVA), and 5-hydroxyindoleacetic (5-HIAA) acids – were determined by HPLC in the cerebral cortex, hippocampus and striatum of the right and left sides of the brain. In the control mice kept both in the group and under the conditions of social isolation, a higher content of DA in the cortex of the left hemisphere has been found. In the other brain structures the monoamine content was symmetric. In the cerebral cortex of the mice in the group, acute hypoxia with hypercapnia led to a right-sided increase in the DA and 5HT levels. At the same time, the DOPAC content decreased in the left cortex. In mice in the group, under the hypoxia with hypercapnia conditions, the DA level in the left hippocampus increased. In the striatum, the content of monoamines and their metabolites did not change significantly. In animals kept for a long time under the conditions of social isolation, hypoxia with hypercapnia no statistically significant changes in the monoamines and their metabolites levels were found. It has been concluded that the preliminary maintenance under the conditions of prolonged social isolation changes the reaction of central monoaminergic systems to acute hypoxia with hypercapnia.


2018 ◽  
Vol 64 (3) ◽  
pp. 257-260 ◽  
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
N.A. Kuritcyna ◽  
N.A. Popkovskii ◽  
...  

Changes in the activity of monoaminergic systems of the left and right hemispheres of the brain after acute hypoxia with hypercapnia were investigated in male albino mice. The concentrations of dopamine (DA), serotonin (5-HT) and their metabolites dihydroxyphenylacetic (DOPAC), homovanilic (HVA) and 5-hydroxyindolacetic (5-HIAA) acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. In the control mice not exposed to hypoxia with hypercapnia, a higher concentration of DA in the left cortex was detected. No asymmetry in the content of other substances has been identified in the investigated structures. Acute hypoxia with hypercapnia led to the right-sided increase of DA and 5-HT levels and to the left-sided reduction DOPAC in the cerebral cortex. Under the condition of hypoxia with hypercapnia, in the hippocampus, the left-sided increase of the DA content was revealed. In the striatum the contents of monoamines and their metabolites were insignificantly changed. It has been concluded that acute hypoxia with hypercapnia causes asymmetric changes in monoaminergic systems of the archicortex and the neocortex.


2012 ◽  
Vol 10 (1) ◽  
pp. 51-53
Author(s):  
Vladimir Vladimirovich Mihkeev ◽  
Vera Vasilievna Marysheva ◽  
Boris Nikolaevich Bogomolov ◽  
Lubov Vladislavovna Zhukova-Williams

The effect of aminothiol antihipoxants amthizol and its analogue VM-606 on the resistance of the SHR mice males to an acute hypoxia with hypercapnia under conditions of isolated functioning of one of the hemispheres of the brain was studied. Antihypoxic agent amthizol 25 mg/kg increases life time of naïve mice by 46.2%. The drug acted on the sham-operated mice more slightly, increasing of their life only on 28.1% (p<0.01). Administration of amthizol under conditions of functioning of the right hemisphere significantly enhanced (+64.8%) the life time of mice. No antihypoxic effect was registered after administration of amthizol to mice with active left hemisphere: the result was the same as in mice without amthizol. Therefore, antihypoxic effect of amthizol was due to its action on the right (but not the left) hemisphere of the brain. VM-606 possessed more antihypoxic activity in comparison with amthizol. After unilateral cortical inactivation, VM-606 increased life time of mice both in active right and active left hemispheres, but in more degree in active right hemisphere. Thus, interhemispheric differences in resistance of mice to hypoxia with hypercapnia were diminished. Therefore, the differences between amthizol and VM-606 are the followings: amthizol inverts interhemispheric relations in hypoxia whereas VM-606 diminishes them.


2014 ◽  
Vol 60 (2) ◽  
pp. 258-263 ◽  
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
E.R. Bychkov ◽  
P.D. Shabanov

The changes in activity of monoaminergic systems of both the right and the left brain hemispheres of the BALB/c male mice after an acute hypoxia with hypercapnia were studied. The concentrations of dopamine, serotonin and their metabolites dihydroxyphenylacetic, homovanilic and 5-hydroxyindolacetic acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. The more high concentration of serotonin was revealed only in the cortex of the left hemisphere in control mice without hypoxia with hypercapnia. The asymmetry in dopamine level was not registered in all structures studied. Acute hypoxia with hypercapnia decreased the dopamine level in the striatum and the serotonin level both in the hippocampus and the brain cortex. The dopamine metabolites level was reduced in the striatum and in the brain cortex of hypoxed mice: both metabolites in the right brain cortex and only dihydroxyphenylacetic acid in the left brain cortex. Serotonin metabolism was decreased in all brain structures studied after hypoxia with hypercapnia in mice. Therefore, serotoninergic system of the brain is more sensitive to acute hypoxia with hypercapnia than dopaminergic system.


2020 ◽  
Vol 65 (6) ◽  
pp. 1196-1202
Author(s):  
С.В. Козин ◽  
◽  
А.А. Кравцов ◽  
Э.И. Злищева ◽  
Л.В. Шурыгина ◽  
...  

The effects of prolonged (42 days) addition of deuterium-depleted water into rat’s diet on the functional state of the central nervous system in normal conditions and under conditions of normobaric hypoxia with hypercapnia were studied. It was also established that the use of deuterium-depleted water both in normal conditions and after exposure to oxidative stress contributes to a significant reduction in the emotional anxiety of animals. Prolonged use of deuterium-depleted water before hypoxic exposure (amnestic effect) helps to maintain learning and memory at the control level, i.e. it has a pronounced protective antiamnestic effect. In normal conditions, deuterium-depleted water does not affect the learning ability of animals.


2020 ◽  
Vol 14 (2) ◽  
pp. 136-149
Author(s):  
I. V. Karpova ◽  
V. V. Mikheev ◽  
V. V. Marysheva ◽  
N. A. Kuritcyna ◽  
E. R. Bychkov ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
pp. 55-63
Author(s):  
Vera V. Marysheva ◽  
Vladimir V. Mikheev ◽  
Petr D. Shabanov

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.


2021 ◽  
Vol 19 (3) ◽  
pp. 17-25
Author(s):  
Dr. Sohail Adnan ◽  
Dr. Mubasher Shah ◽  
Dr. Syed Fahim Shah ◽  
Dr. Fahad Naim ◽  
Dr. Akhtar Ali ◽  
...  

Background: Consciousness has remained a difficult problem for the scientists to explore its relationship to the brain activity. This is the first paper that presents the significance of focal areas of the cerebral cortex for consciousness. Objectives: To determine if consciousness is produced by the activity of the whole brain or one of its focal areas. Methods: We have performed a prospective cross-sectional study in eighty patients of acute ischemic stroke. The neurovascular territory of the middle cerebral artery (MCA) was sectioned into four similar areas. The association of any of these focal areas to consciousness was observed after their dysfunction with ischemic strokes. Results: Of the eighty patients, 57.5 % were males and 42.5 % were females. Mean age was 63 years ± 7 SD. The righthanded patients were 90 % (72) of the whole sample. Focal areas of the right MCA were generally less prone to consciousness disorder. Average statistics of the focal infarctions of the right MCA showed no tendency for consciousness disorder on the Glasgow coma scale (GCS) [Mean GCS of all focal areas; 14.5, SD; 0.71, 95 % CI; 14.27 to 14.72, P= 0.0000004]. Altered consciousness with focal infarctions of the territory of left MCA was also less likely [Mean GCS of all focal areas; 14.2, SD; 1.01, 95 % CI; 13.88 to 14.51, P= 0.0004]. Conclusion: Consciousness is not determined by the activity of a focal area of the cerebral cortex. Perhaps, we get our consciousness from the activity of “Neuronal Network of Coordination”.


2001 ◽  
Vol 13 (1) ◽  
pp. 72-89 ◽  
Author(s):  
Apostolos P. Georgopoulos ◽  
Kenneth Whang ◽  
Maria-Alexandra Georgopoulos ◽  
Georgios A. Tagaris ◽  
Bagrat Amirikian ◽  
...  

We studied the brain activation patterns in two visual image processing tasks requiring judgements on object construction (FIT task) or object sameness (SAME task). Eight right-handed healthy human subjects (four women and four men) performed the two tasks in a randomized block design while 5-mm, multislice functional images of the whole brain were acquired using a 4-tesla system using blood oxygenation dependent (BOLD) activation. Pairs of objects were picked randomly from a set of 25 oriented fragments of a square and presented to the subjects approximately every 5 sec. In the FIT task, subjects had to indicate, by pushing one of two buttons, whether the two fragments could match to form a perfect square, whereas in the SAME task they had to decide whether they were the same or not. In a control task, preceding and following each of the two tasks above, a single square was presented at the same rate and subjects pushed any of the two keys at random. Functional activation maps were constructed based on a combination of conservative criteria. The areas with activated pixels were identified using Talairach coordinates and anatomical landmarks, and the number of activated pixels was determined for each area. Altogether, 379 pixels were activated. The counts of activated pixels did not differ significantly between the two tasks or between the two genders. However, there were significantly more activated pixels in the left (n = 218) than the right side of the brain (n = 161). Of the 379 activated pixels, 371 were located in the cerebral cortex. The Talairach coordinates of these pixels were analyzed with respect to their overall distribution in the two tasks. These distributions differed significantly between the two tasks. With respect to individual dimensions, the two tasks differed significantly in the anterior-posterior and superior-inferior distributions but not in the left-right (including mediolateral, within the left or right side) distribution. Specifically, the FIT distribution was, overall, more anterior and inferior than that of the SAME task. A detailed analysis of the counts and spatial distributions of activated pixels was carried out for 15 brain areas (all in the cerebral cortex) in which a consistent activation (in ≥ 3 subjects) was observed (n = 323 activated pixels). We found the following. Except for the inferior temporal gyrus, which was activated exclusively in the FIT task, all other areas showed activation in both tasks but to different extents. Based on the extent of activation, areas fell within two distinct groups (FIT or SAME) depending on which pixel count (i.e., FIT or SAME) was greater. The FIT group consisted of the following areas, in decreasing FIT/SAME order (brackets indicate ties): GTi, GTs, GC, GFi, GFd, [GTm, GF], GO. The SAME group consisted of the following areas, in decreasing SAME/FIT order: GOi, LPs, Sca, GPrC, GPoC, [GFs, GFm]. These results indicate that there are distributed, graded, and partially overlapping patterns of activation during performance of the two tasks. We attribute these overlapping patterns of activation to the engagement of partially shared processes. Activated pixels clustered to three types of clusters: FIT-only (111 pixels), SAME-only (97 pixels), and FIT + SAME (115 pixels). Pixels contained in FIT-only and SAME-only clusters were distributed approximately equally between the left and right hemispheres, whereas pixels in the SAME + FIT clusters were located mostly in the left hemisphere. With respect to gender, the left-right distribution of activated pixels was very similar in women and men for the SAME-only and FIT + SAME clusters but differed for the FIT-only case in which there was a prominent left side preponderance for women, in contrast to a right side preponderance for men. We conclude that (a) cortical mechanisms common for processing visual object construction and discrimination involve mostly the left hemisphere, (b) cortical mechanisms specific for these tasks engage both hemispheres, and (c) in object construction only, men engage predominantly the right hemisphere whereas women show a left-hemisphere preponderance.


2017 ◽  
Vol 15 (2) ◽  
pp. 23-30
Author(s):  
Inessa V Karpova ◽  
Evgenii R Bychkov ◽  
Vera V Marysheva ◽  
Vladimir V Mikheyev ◽  
Petr D Shabanov

Objective. In the course of the study, the effect of oxytocin on the behavior and level of monoamines of the brain in aggressive male isolates of the initially low-aggressive C57Bl/6 line with similar indices of highly aggressive white outbred mice was compared. Methods. In experiments on isolated male mice of the low-aggressive C57Bl/6 line and highly aggressive white outbred mice, the effects of oxytocin on the aggressive behavior and the activity of monoaminergic systems of the left and right cerebral hemispheres was investigated. After prolonged social isolation, the male mice, who attacked in the resident-intruder test, were selected for further research. Oxytocin (5 IU/ml, 20μl) was admitrated intranasally. Control animals was treated with saline. With the HPLC-method, in the cerebral cortex, hippocampus, olfactory tubercle and striatum of the left and right sides of the brain the concentrations of dopamine, norepinephrine, serotonin and their metabolites of dioxyphenylacetic, homovaniline and 5-hydroxyindoleacetic acids were measured. Results. Among the male isolates of the C57Bl/6 line, the proportion of aggressive individuals was 56.5%, and among white outbred mice 87.5%. The investigated lines also differed in the attack latency time: aggressive C57Bl/6 mice attacked an average on the 113.1±23.5 second, while in white outbred mice the attack followed on the 35.3±14.7 second (p < 0.01). In the aggressive male isolates of the C57Bl/6 line, which received intranasally saline solution, the content of serotonin and 5-hydroxyindoleacetic acid in the hippocampus was significantly higher on the right. In C57Bl/6, oxytocin reduced the manifestation of aggression caused by prolonged social isolation (p < 0.05), but had no absolute ability to stop this type of behavior. Under its influence, the level of dopamine in the left cortex (p = 0.054), as well as serotonin content in the right hippocampus (p < 0.05) and in the left striatum (p < 0.05) decreased. In addition, the use of oxytocin in C57Bl/6 neutralized the asymmetry of serotonin and 5-hydroxyindoleacetic acid levels in the hippocampus. At the same time there was an asymmetry in the content of dopamine in the cerebral cortex with the predominance of this mediator in the right hemisphere (p < 0.05). In male isolates of highly aggressive white outbred mice, the effect of oxytocin on behavior was not found. However, in these animals oxytocin caused certain changes in monoaminergic systems of the brain. Under the action of oxytocin, the inicial right-sided asymmetry of the level of dopamine metabolites in the striatum and left-sided asymmetry in the level of serotonin in the cortex disappeared. Oxytocin caused an increase in the content of 5-hydroxyacetic acid in the right striatum (p < 0.05) and norepinephrine in the left hippocampus (p < 0.05). In addition, white outbred mice under the influence of oxytocin developed asymmetry with the predominance of norepinephrine in the right olfactory tubercle (p < 0.05). Conclusions. It can be assumed that relatively weak changes in the state of serotonergic and dopaminergic systems against the background of high reactivity of the noradrenergic system are a feature of the reaction of the brain of highly aggressive animals to oxytocin. The data obtained are discussed in terms of the lateralization of neurotransmitter systems responsible for intraspecific aggression caused by prolonged social isolation. (For citation: Karpova IV, Bychkov ER, Marysheva VV, et al. The effect of oxytocin on the level and monoamines turnover in the brain of isolated mice of high- and low-aggressive lines. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(2):23-30. doi: 10.17816/RCF15223-30).


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