Q95386900 Dotaz Zobrazit nápovědu
Reactive oxygen species (ROS) are common products of the physiological metabolic reactions, which are associated with cell signaling and with the pathogenesis of various nervous disorders. The brain tissue has the high rate of oxidative metabolic activity, high concentration of polyunsaturated fatty acids in membrane lipids, presence of iron ions and low capacity of antioxidant enzymes, which makes the brain very susceptible to ROS action and lipid peroxidation formation. Membranes of brain cortex show a higher production of thiobarbituric acid-reactive substances (TBARS) in prooxidant system (ADP.Fe(3+)/NADPH) than membranes from the heart or kidney. Lipid peroxidation influences numerous cellular functions through membrane-bound receptors or enzymes. The rate of brain cortex Na(+),K(+)-ATPase inhibition correlates well with the increase of TBARS or conjugated dienes and with changes of membrane fluidity. The experimental model of short-term hypoxia (simulating an altitude of 9000 m for 30 min) shows remarkable increase in TBARS in four different parts of the rat brain (cortex, subcortical structures, cerebellum and medulla oblongata) during the postnatal development of Wistar rat of both sexes. Young rats and males are more sensitive to oxygen changes than adult rats and females, respectively. Under normoxia or hypobaric hypoxia both ontogenetic aspects and sex differences play a major role in establishing the activity of erythrocyte catalase, which is an important part of the antioxidant defense of the organism. Rats pretreated with L-carnitine (and its derivatives) have lower TBARS levels after the exposure to hypobaric hypoxia. The protective effect of L-carnitine is comparable with the effect of tocopherol, well-known reactive species scavenger. Moreover, the plasma lactate increases after a short-term hypobaric hypoxia and decreases in L-carnitine pretreated rats. Acute hypobaric hypoxia and/or L-carnitine-pretreatment modify serum but not brain lactate dehydrogenase activity. The obtained data seem to be important because the variations in oxygen tension represent specific signals of regulating the activity of many specific systems in the organism.
- MeSH
- hypoxie metabolismus MeSH
- karnitin metabolismus MeSH
- krysa rodu rattus MeSH
- látky reagující s kyselinou thiobarbiturovou metabolismus MeSH
- peroxidace lipidů fyziologie MeSH
- pohlavní dimorfismus MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- stárnutí metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Developmental study of dopaminergic and noradrenergic systems in child psychiatric disorders are rare. DBH activity is one of noradrenergic biochemical marker that is correlate in psychiatry to clinical and genetic data. OBJECTIVES: The main aim of the present study was to measure DBH activity at the onset of acute schizophrenia and depressive disorder in children and adolescents without pharmacological treatment and to compare these values with DBH activity in healthy controls. The authors also investigated untreated ADHD children. METHODS: We examined 42 control healthy children, 15 children non-treated with acute schizophrenia, 15 non-treated children with acute depressive disorders and 30 non-treated ADHD children, all in age 7-14. Plasma DBH level was provided by Nagatsu (1972; 1974). Depressed children were reexamined after clinical remission. RESULTS: DBH activity is statistically significantly decreased in non-treated depressive disorder and ADHD in children and adolescents. DBH activity is normalised during antidepressant therapy in child depression. Child schizophrenia patients present with normal DBH activity. CONCLUSION: These results are similar to the results that have been observed in adult patients with schizophrenia and depression and in previous studies of DBH activity in children with ADHD. These results also indicate hypoactivity of the noradrenergic system in children with ADHD and depression.
- MeSH
- biologické markery metabolismus MeSH
- dítě MeSH
- dopamin-beta-hydroxylasa krev MeSH
- duševní poruchy krev enzymologie MeSH
- hyperkinetická porucha krev enzymologie MeSH
- lidé MeSH
- mladiství MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In albino rats (Wistar) aged 10 and 14 days of postnatal life, experiments were performed, in which the intensity of lipoperoxidative processes in cerebral cortex and medulla oblongata in four experimental series was measured and compared (between males and females, the effect of hypobaric hypoxia corresponding 7000 m of altitude and lasting 20 minutes and the effect of short-term starvation i.e. for 24 hours between the day 5th and 6th of postnatal life and finally between females and males exposed to the combination of mentioned stressors). The hypoxia evokes significantely greater increase of lipoperoxidative processes in brain tissue of males. The short-term starvation affected more the oxygen radicals production in females. The exposition to normobaric oxygen atmosphere enhanced the lipid peroxidative processes also significantely in the brain tissue of males of various age (as compared with females). Male and female rats (Wistar), 5 days old and full grown rats were used in experiments in which the effect of i.p. administered adrenaline (0,15 mg/kg body weight) on the ascorbic acid content in various parts of the brain and plasma was followed. The significant decrease of ascorbic acid content in the brain in females (increase in the plasma) and exactly the opposite result in males (full grown) were described. In rats, distinct developmental changes in plasma dopamin betahyd- roxylase (E.C.1.14.17.1.) activity and significant differences between sexes were established (higher activity in females). Stressors such as hypoxia and short-term starvation in young as well in adults-evokes a decrease of DBH plasmatic activity.
- Klíčová slova
- brain, oxygen radicals, sex-differences, ascorbic acid, dopamine-beta-hydroxylase, ontogeny,
- Publikační typ
- abstrakty MeSH
Koenzym Q (CoQ) vedle své základní úlohy elektronového přenašeče spojeného se syntézou ATP zasahuje do mnoha dalších funkcí v organizmu. Redukovaná forma CoQ působí jako silný antioxidant, což se využívá v celé řadě patologií včetně chorob nervového systému. Cílem Studie bylo stanovit vhodné koncentrační rozmezí derivátů CoQ pro optimální obranu proti poškození membrán mozkové kůry potkana lipidovou peroxidací (v systému Fe2 + askorbát). Poškození membrán jsme hodnotily metodou stanovující látky reagující s kyselinou thiobarbiturovou (TBARS). Potvrdily jsme signifikantní snížení poškození membrán v přítomnosti derivátů CoQ s krátkým isoprenylovým řetězcem (CoQj a CoQ^) i se syn¬ terickým derivátem idebenonem, naopak nejmenší protekční účinky jsme nalezly u CoQ4. Výsledky studie mohou přispět k výzkumu v oblasti vývoje léků pro léčbu nemocí, kde je třeba odstranit oxidační stres.
Coenzyme Q (CoQ) beside its fundamental role of an electron carrier associated with ATP production is involved in many other functions in organism. The reduced form of CoQ works as a strong anti- oxidant agent which is used in a wide range of pathological states inclu- ding nervous system. The aim of the study was to specify the appropriate concentration range of CoQ derivatives for the best antioxidant defense of rat cerebral cortex membranes against lipid peroxidation damage (in the system Fe 2+ + ascorbate). Membrane damage was evaluated by the method measuring thiobarbituric acid-reactive substances (TBARS). We confirmed the significant decrease of membrane damage in the presence of CoQ derivatives with the short isoprenyl chain (CoQ 1 a CoQ 2 ) and synthetic derivative idebenone, whereas we found the smallest protection effect in the presence of CoQ 4 . Our results can help in the development of new drugs for the treatment of diseases where the oxidative stress is necessary to remove.
- Klíčová slova
- lipidová peroxidace, látky reagující s kyselinou thiobarbiturovou (TBARS), membrány mozkové kůry, deriváty koenzymu Q,
- Publikační typ
- abstrakty MeSH
In our previous studies we have found both an increase of lipid peroxidation damage (expressed as levels of thiobarbituric acid-reactive substances) in brain and plasma lactate concentration in 21-day-old rats after a 30-min exposure to hypobaric hypoxia. Pretreatment of rats with L-carnitine decreased both parameters. The aim of our present study was to determine if the L-carnitine-dependent decrease of plasma lactate could be due to a modification of lactate dehydrogenase (LDH) activity. We followed brain and blood serum LDH activity of 14-, 21- and 90-day-old Wistar rats. We found an increase of brain LDH activity with age. However, we did not observe any significant differences in LDH activity after exposure to hypobaric hypoxia or L-carnitine pretreatment. In contrast to brain, serum LDH activity did not show any clear age-dependence. The hypoxia exposure increased LDH activity of 21-day-old rats only. Pretreatment of rats with L-carnitine decreased serum LDH activity of 21- and 90-day-old rats probably due to membrane stabilizing role of L-carnitine. In conclusions, acute hypobaric hypoxia and/or L-carnitine pretreatment modified serum but not brain LDH activity.
- MeSH
- finanční podpora výzkumu jako téma MeSH
- hypoxie buňky fyziologie MeSH
- karnitin terapeutické užití MeSH
- látky reagující s kyselinou thiobarbiturovou farmakokinetika toxicita MeSH
- mozek fyziologie patofyziologie MeSH
- peroxidace lipidů genetika účinky léků MeSH
- potkani Wistar anatomie a histologie MeSH
- reaktivní formy dusíku metabolismus škodlivé účinky MeSH
- reaktivní formy kyslíku metabolismus škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
ADHD (attention hyperactivity disorder) is a polygenetic disorder with various candidate genes. At this time, more than thirty dopaminergic, noradrenergic, serotonergic and GABA-ergic genes are known. The research of only some candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought relatively consistent results confirming the heredity of ADHD syndromes. The results of research of other genes (DRD2, DRD3, MAO, ADR2A, GABA A3, GABA B3) are not clear yet. This paper summarizes the most important genetic data in correlations with biochemical periphery parameters (especially for DBH, HVA, MHPG, serotonin). Hypothetically, certain subgroups of ADHD may be identified by correlation of biochemical characteristics and some candidate genes. The paper discusses some implications for future research. Review.
