Effect of stress factors on carboxypeptidase H activity in areas of the rat brain]

It is established that carboxypeptidase H activity increases as affected by various stress factors in the rat brain departments. The increase of the enzyme activity because of the emotional-pain stress is of continuous character. Possible role of carboxypeptidase H in the development of the stress response is discussed.     

Antistress effect of dimethyl sulfoxide in the rat

Administration of scavenger of hydroxyl radicals--dimethylsulfoxide (1 g/kg intraperitoneally, daily for 3 weeks) did not lead to any significant changes in animals behaviour in the open field and in visceral functions (arterial pressure, respiratory rate, heart rate) but prevented shifts of these characteristics caused by chronic 3-week emotional-pain stress. In rats injected with dimethylsulfoxide, an increase was observed of superoxide dismutase activity in the brain and blood serum. Molecular mechanisms are discussed of antistress action of dimethylsulfoxide (scavenge of hydroxyl radicals, activation of superoxide dismutase) and possible role of hydroxyl radicals in realization of damaging action of stress on the organism.     

Apha-tocopherol in a complex with dimethyl sulfoxide--an agent possessing highly effective adaptogenic action in chronic emotional-pain stress in rats

Alpha-tocopherol (5 mg/kg) administered perorally with dimethyl sulfoxide (50 mg/kg) in chronic emotional pain stress in rats possesses an effective antistress action, exceeding the effects of these drugs administered separately. Their prophylactic complex administration prevents the hypertension produced by stress, disturbance of reactivity of the vegetative nervous system during functional load, change of the behaviour in the open field. Adaptogenic action of the drugs is accompanied by a reduction of the content of free-radical oxidation products and by raising of superoxide scavenging activity in the brain and blood serum, by raising of phospholipids content, lowering of cholesterol content and of the ratio of cholesterol phospholipids in the brain extracts.     

State of the free-radical oxidation system in normobaric hypoxia]

The experiments on the rats have revealed that 7-hour action of 10% hypoxic gas mixture (HGM-10) exerts no effect on the parameters of Fe(2+)-induced chemiluminescence and rate of accumulation of TBA-active products in the heart, liver, kidney, brain tissues and blood plasma. Two-week adaptation to intermittent effect of HGM-10 causes some activation of free-radical oxidation recorded in blood plasma and the more pronounced increase in power of the endogenic antioxidant system. It is assumed that the revealed changes in the state of the homeostatic system of free-radical oxidation and antiradical protection of the organism are of importance in the mechanism of the known preventive and curative action of intermittent normobaric hypoxia.     

Inhibition of free-radical lipid oxidation in the mechanisms of immediate and long-term adaptation to stress

The literary data and own results concerning the stages of free radical lipid oxidation inhibition during the adaptation of animals to stress are reviewed. Using the chronic stress models such as immobilization, experimental neurosis, it has been shown, that in general adaptation syndrome the stage of permanent adaptation to stress corresponds to a permanent inhibition of free radical processes in animal tissues. This stage is accompanied by the activation of superoxide radical scavenging and corresponding changes of lipid composition. similar results are obtained on the model of the development of permanent compensation processes after brain injury. Studying the acute stress it has been found, that during first minutes the inhibition of lipid peroxidation which precedes its further activation takes place. This stage corresponds to the realization of urgent adaptation phase to stress. The role of inhibition of free radical processes in mechanisms of urgent and permanent adaptation to stress is under discussion.     

Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide.

Amyloid beta-peptide (Abeta) is heavily deposited in the brains of Alzheimer's disease (AD) patients. Free-radical oxidative stress, particularly of neuronal lipids, proteins and DNA, is extensive in those AD brain areas in which Abeta is abundant. Recent research suggests that these observations might be linked, and it is postulated that Abeta-induced oxidative stress leads to neurodegeneration in AD brain. Consonant with this postulate, Abeta leads to neuronal lipid peroxidation, protein oxidation and DNA oxidation by means that are inhibited by free-radical antioxidants. Here, we summarize current research on phospholipid peroxidation, as well as protein and DNA oxidation, in AD brain, and discuss the potential role of Abeta in this oxidative stress.     

Characteristics of free-radical oxidation and antiradical protection of the brain in adaptation to chronic stress

During the phase of long-lasting adaptation to chronic emotional painful stress three stages have been distinguished on the basis of physiological and neurobiochemical data. The first stage (1 week of stress)--transition from urgent to long-lasting adaptation--corresponds to labilization of vegetative indices, predominance of fear reactions and suppression of research behaviour in rats, inhibition of lipid peroxidation, activation of superoxide scavenging activity, decrease in cholesterol content in brain lipids. The second stage (2 weeks of stress)--long-lasting adaptation--is characterized by normalization of the behaviour, stabilization of high blood pressure, maximum brain antiradical activity and low level of lipid peroxidation. The third stage (3 weeks of stress)--transition from long-lasting adaptation to exhaustion--is characterized by blood pressure lowering, disturbed regulation of vegetative functions, behavioural hyperactivity in the open field, increased lipid peroxidation and decreased phospholipid content.     

Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid β-peptide

Amyloid β-peptide (Aβ) is heavily deposited in the brains of Alzheimer's disease (AD) patients. Free-radical oxidative stress, particularly of neuronal lipids, proteins and DNA, is extensive in those AD brain areas in which Aβ is abundant. Recent research suggests that these observations might be linked, and it is postulated that Aβ-induced oxidative stress leads to neurodegeneration in AD brain. Consonant with this postulate, Aβ leads to neuronal lipid peroxidation, protein oxidation and DNA oxidation by means that are inhibited by free-radical antioxidants. Here, we summarize current research on phospholipid peroxidation, as well as protein and DNA oxidation, in AD brain, and discuss the potential role of Aβ in this oxidative stress.     

Damage to the Ca2+-transport system of cardiac sarcoplasmic reticulum during emotion-pain stress

The influence of emotional-pain stress on the properties of the sarcoplasmic reticulum Ca2+-transporting system of the rat heart muscle was studied. The decrease of the Ca2+-dependent component of the Ca2+, Mg2+-ATPase activity, Ca2+-binding capacity and the rate of Ca2+-transport was found in the animals after stress. These alterations in the Ca2+-transporting system were caused by lipid peroxidation and could be prevented by the antioxidant ionol.     

Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function

Chronic oxidative stress has been causally linked to several neurodegenerative disorders. As sensitivity for oxidative stress greatly differs between brain regions and neuronal cell types, specific cellular mechanisms of adaptation to chronic oxidative stress should exist. Our objective was to identify molecular mechanisms of adaptation of neuronal cells after applying chronic sublethal oxidative stress. We demonstrate that cells resistant to oxidative stress exhibit altered cholesterol and sphingomyelin metabolisms. Stress-resistant cells showed reduced levels of molecules involved in cholesterol trafficking and intracellular accumulation of cholesterol, cholesterol precursors, and metabolites. Moreover, stress-resistant cells exhibited reduced SMase activity. The altered lipid metabolism was associated with enhanced autophagy. Treatment of stress-resistant cells with neutral SMase reversed the stress-resistant phenotype, whereas it could be mimicked by treatment of neuronal cells with a specific inhibitor of neutral SMase. Analysis of hippocampal and cerebellar tissue of mouse brains revealed that the obtained cell culture data reflect the in vivo situation. Stress-resistant cells in vitro showed similar features as the less vulnerable cerebellum in mice, whereas stress-sensitive cells resembled the highly sensitive hippocampal area. These findings suggest an important role of the cell type-specific lipid profile for differential vulnerabilities of different brain areas toward chronic oxidative stress.     

Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events

Stressful events during adulthood are potent adverse environmental factors that can predispose individuals to psychiatric disorders, including depression; however, many individuals exposed to stressful events can adapt and function normally. While stress vulnerability may influence depression, the molecular mechanisms underlying the susceptibility and adaptation to chronic stress within the brain are poorly understood. In this study, two genetically distinct mouse strains that exhibit different behavioral responses to chronic stress were used to demonstrate how the differential epigenetic status of the glial cell-derived neurotrophic factor (Gdnf) gene in the ventral striatum modulates susceptibility and adaptation to chronic stress. Our results suggest that the histone modifications and DNA methylation of the Gdnf promoter have crucial roles in the control of behavioral responses to chronic stress. Our data provide insights into these mechanisms, suggesting that epigenetic modifications of Gdnf, along with genetic and environmental factors, contribute to behavioral responses to stress.     

Free radicals in exhaustive physical exercise: mechanism of production, and protection by antioxidants

Moderate exercise is a healthy practice. However, exhaustive exercise generates free radicals. This can be evidenced by increases in lipid peroxidation, glutathione oxidation, and oxidative protein damage. It is well known that activity of cytosolic enzymes in blood plasma is increased after exhaustive exercise. This may be taken as a sign of damage to muscle cells. The degree of oxidative stress and of muscle damage does not depend on the absolute intensity of exercise but on the degree of exhaustion of the person who performs exercise. Training partially prevents free radical-formation in exhaustive exercise. Treatment with antioxidants such as vitamins C or E protects in part against free radical-mediated damage in exercise. Xanthine oxidase is involved in free-radical formation in exercise in humans and inhibition of this enzyme with allopurinol decreases oxidative stress and muscle damage associated with exhaustive exercise. Knowledge of the mechanism of free-radical formation in exercise is important because it will be useful to prevent oxidative stress and damage associated with exhaustive physical activity.     

Possible role of hypoxia and lipid peroxidation in the development of a neurosis-like condition in the rat

The chronic emotional pain stress resulting in a development of neurosis-like state in rats induced an increase of arterial pressure and change of the cardiac rate dynamics under the conditions of functional load. An increase of cardiac mass was also seen without change of masses of the thymus, adrenal glands and the spleen. The rise of activity of cytochromeoxidase and activation of peroxide lipide oxidation (by malonate dialdehyde level) were observed in the cerebral cortex and the hippocampus of neurotized rats. Injection of antioxidant F-801 before each emotional pain stress trial prevented vegetative disturbances, cardiac hypertrophy, and increase of oxidative activity in the brain. The role of peroxide lipide oxidation and that of the factor of hypoxia in development of disturbances caused by neurotization were discussed.     

Asymmetry of aging of the large hemispheres of the rat brain

The dynamics of the accumulation of free-radical oxidation products in the brain hemispheres of rats in rate ontogenesis was studied. Multiphase changes in the concentration of products in the right and left hemispheres in different age groups were registered. Significant differences in the contents of hydroperoxides, Schiff's bases of phospholipids and lipofuscin in brain hemispheres revealed, which correlates with different rate of ageing of hemispheres.     

Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants.

The responses to oxidative stress induced by chronic exercise (8-wk treadmill running) or acute exercise (treadmill running to exhaustion) were investigated in the brain, liver, heart, kidney, and muscles of rats. Various biomarkers of oxidative stress were measured, namely, lipid peroxidation [malondialdehyde (MDA)], protein oxidation (protein carbonyl levels and glutamine synthetase activity), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), and endogenous antioxidants (ascorbic acid, alpha-tocopherol, glutathione, ubiquinone, ubiquinol, and cysteine). The predominant changes are in MDA, ascorbic acid, glutathione, cysteine, and cystine. The mitochondrial fraction of brain and liver showed oxidative changes as assayed by MDA similar to those of the tissue homogenate. Our results show that the responses of the brain to oxidative stress by acute or chronic exercise are quite different from those in the liver, heart, fast muscle, and slow muscle; oxidative stress by acute or chronic exercise elicits different responses depending on the organ tissue type and its endogenous antioxidant levels.     

The role for the hippocampus in the biorhythmical behavior

The hippocampus as a important limbic structure has polyfunction properties among which take place chronotropic activity. It is showed in instability of different biological rhythms that provided for adaptation of organism to changing environment conditions. Chronotropic activity may be depenede from reciprocal connections of the hippocampus with brain rhythmorganizing structures (suprachiasmatic nuclei of hypothalamus and pineal gland). Increase of hippocampal excitability after chronic stress are produce disorganization of some rhythmic processes and followed neurosis or psychical depression. Psychotropic drugs (anxiolytics and antidepressants) by means of intensified of hippocampal inhibitory mechanisms (previously GABA and 5-HT) are stabilized of biorhythms what determined their specific anxiolytic and antidepressant effects.     

Free-radical processes and the antioxidant system in the realization of the recovery function of sleep

The somnological status of test subjects was assessed. The content of malonic dialdehyde, total peroxidase activity, and concentration of uric acid, urea, and total protein in the saliva of students with insomnia and age-matched (20- to 23-year-old) healthy students were determined during everyday studies and summer exams. It was found that emotional (examination) stress intensifies free-radical processes and leads to a compensatory increase in the activity of the nonenzymatic antioxidant system in the saliva of students. Insomnia is accompanied by an increased level of free-radical processes and increased total protein content in the saliva of test subjects. The recovery anabolic function of sleep is realized via activation of protein synthesis and involvement of low-molecular-weight nonenzymatic antioxidant compounds (uric acid and urea) in the defensive responses of the body under conditions of a significant increase in the intensity of free-radical processes during examination stress combined with insomnia.     

Increased enzymatic activity of antioxidant protection of the heart in the adaptation of rats to short-term stress exposure

It has been shown that adaptation to short-term emotional-painful stresses leads to an increase in antioxidant enzyme activities but does not change vitamin E content in the myocardium. The most labile enzyme was catalase (35% increase). During stress in nonadapted animals the enzyme activity decreased, as compared to the control, while in the group of adapted animals with subsequent stress the activity was even higher than in the control. During initiation of lipid peroxidation in the heart homogenates in vitro there was a 3-fold increase and a 1%-fold decrease in the oxidation intensity in rats exposed to stress and in adapted animals, respectively. The role of adaptation activation of cardiac antioxidant system in the prevention of stress-induced heart damage is discussed.     

Effect of antioxidants on the indices of free-radical lipid oxidation in the testes of rats of different ages and on the reproductive capacity in chronic multiple antioxidant deficiency

The free-radical oxidation level of lipids in the rat's testicles of different age under the conditions of chronic and multiple antioxidant insufficiency has been studied, as well as the reproductive ability of male rats, kept at the nonantioxidant ration. The increase of free radical oxidation lipids in the testicles of animals with chronic multiple antioxidant insufficiency and the decrease of their reproductive ability has been observed. The antioxidant complex in such conditions had a defensive effect. The obtained results serve as the basis of the antioxidant use as the means of normalising the reproductive functions in males during period of low receipt and high expense of alimentary oxidants.