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Sample records for brain catecholamine levels

  1. Catecholamines and cognition after traumatic brain injury.

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    Jenkins, Peter O; Mehta, Mitul A; Sharp, David J

    2016-09-01

    Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person's catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain 'networks' that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner.

  2. Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson’s Disease

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    Yamamoto, Tatsuya; Uchiyama, Tomoyuki; Higuchi, Yoshinori; Asahina, Masato; Hirano, Shigeki; Yamanaka, Yoshitaka; Kuwabara, Satoshi

    2015-01-01

    Aims Although subthalamic nucleus deep brain stimulation (STN-DBS) is effective in patients with advanced Parkinson’s disease (PD), its physiological mechanisms remain unclear. Because STN-DBS is effective in patients with PD whose motor symptoms are dramatically alleviated by L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, the higher preoperative catecholamine levels might be related to the better clinical outcome after surgery. We aimed to examine the correlation between the preoperative catecholamine levels and postoperative clinical outcome after subthalamic nucleus deep brain stimulation. The effectiveness of STN-DBS in the patient who responded well to dopaminergic medication suggest the causal link between the dopaminergic system and STN-DBS. We also examined how catecholamine levels were modulated after subthalamic stimulation. Methods In total 25 patients with PD were enrolled (Mean age 66.2 ± 6.7 years, mean disease duration 11.6 ± 3.7 years). Mean levodopa equivalent doses were 1032 ± 34.6 mg before surgery. Cerebrospinal fluid and plasma catecholamine levels were measured an hour after oral administration of antiparkinsonian drugs before surgery. The mean Unified Parkinson’s Disease Rating Scale scores (UPDRS) and the Parkinson’s disease Questionnaire-39 (PDQ-39) were obtained before and after surgery. Of the 25 patients, postoperative cerebrospinal fluid and plasma were collected an hour after oral administration of antiparkinsonian drugs during on stimulation at follow up in 11 patients. Results Mean levodopa equivalent doses significantly decreased after surgery with improvement in motor functions and quality of life. The preoperative catecholamine levels had basically negative correlations with postoperative motor scores and quality of life, suggesting that higher preoperative catecholamine levels were related to better outcome after STN-DBS. The preoperative plasma levels of L-DOPA had significantly negative correlations with

  3. Plasma levels of brain derived-neurotrophic factor and catecholamine metabolites are increased during active phase of psychotic symptoms in CNS lupus: a case report.

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    Ikenouchi, Atsuko; Yoshimura, Reiji; Ikemura, Naomi; Utsunomiya, Kensuke; Mitoma, Masae; Nakamura, Jun

    2006-09-30

    In the present study, the authors reported a case of systemic lupus erythematosus (SLE) with central nervous system involvement (CNS lupus). The authors also longitudinally investigated plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in the patient, and found that plasma levels of BDNF, 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were raised in accordance with the severity of psychotic symptoms in this case of CNS lupus. These results suggest that it is useful to measure plasma levels of BDNF and the catecholamine metabolites in order to predict the severity of psychotic symptoms in CNS lupus and to provide a differential diagnosis from that of steroid-induced psychosis.

  4. Attenuation of stress-elicited brain catecholamines, serotonin and plasma corticosterone levels by calcined gold preparations used in Indian system of medicine.

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    Shah, Zahoor Ahmad; Gilani, Rabia Afzal; Sharma, Pragya; Vohora, Shashi Bharat

    2005-06-01

    Problems associated with mental health have increased tremendously in modern times. The search for effective and safe alternatives should, therefore, be pursued vigorously. Forced immobilization is one of the best explored models of stress in rats and the role of corticosterone, serotonin (5-HT) and catecholamines, i.e. norepinephrine, epinephrine, dopamine is well documented. We investigated the therapeutic potential of two gold preparations (Ayurvedic Swarna Bhasma and Unani Kushta Tila Kalan) in restraint induced stress at different time points of 1 hr, 2 hr and 4 hr. We pretreated rats with two gold preparations, Ayurvedic Swarna Bhasma and Unani Kushta Tila Kalan (25 mg/kg, orally for 10 days) prior to restraint stress. Brain catecholamine, serotonin and plasma corticosterone levels were determined following 1, 2 and 4 hr restraint stress, using HPLC and also plasma corticosterone using luminescence spectrophotometry. Gold preparations restored restraint stress-induced elevation in levels of brain catecholamines (norepinephrine, epinephrine and dopmine), 5-HT and plasma corticosterone to near normal levels. Gold, widely used in modern medicine for the treatment of rheumatoid arthritis, is highly valued for various medicinal uses in Indian systems of medicine. Traditional gold preparations are attributed with tonic/rejuvenating and antioxidant properties. Our earlier studies revealed interesting analgesic, immunostimulant, adaptogenic and glycogen sparing properties in these preparations, but their effects in stress and depression have not been investigated yet. Significant restoration of altered values to near normal levels suggest potentials for gold preparations in stress and depression.

  5. Effect of γ-ethyl-γ-phenyl-butyrolactone (EFBL, anticonvulsant and hypnotic drug, on mouse brain catecholamine levels

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    Rasgado Lourdes A. Vega

    2017-06-01

    Full Text Available γ-Ethyl-γ-phenyl-butyrolactone (EFBL is a structural combination of the anticonvulsant γ-hydroxy-γ-ethyl-γ-phenylbutyramide (HEPB and the hypnotic γ-butyrolactone (GBL, which inherits both properties. To clarify its mechanism of action, the effects of EFBL, GBL and HEPB on dopamine (DA and noradrenaline (NA brain levels were investigated. Influences of chlorpromazine, phenelzine and aminooxyacetic acid were also studied. EFBL increased DA in a dose-dependent manner, remaining enhanced by 80 % over a period of 24 h and augmented NA by 54 % one hour after treatment. HEPB increased DA and NA approximately 2-fold after the first hour. GBL raised DA and NA after three and 24 h, resp. EFBL reversed chlorpromazine effects but potentiated those of phenelzine on DA. Amino-oxyacetic modified neither DA nor NA brain levels, not even in the presence of EFBL. The anticonvulsant and hypnotic properties of EFBL are attributed to its effect on presynaptic dopaminergic receptors and its lasting effect on ethyl and phenyl radicals that hinder its degradation. The results support the role of DA and NA in regulating seizure activity in the brain and indicate that EFBL offers a potential treatment for refractory epilepsy without complementary drugs and Parkinson’s disease, without the drawbacks of oral therapies.

  6. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

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    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  7. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

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    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  8. [Plasma catecholamines in consciousness recovery in patients with severe traumatic brain injury].

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    Aleksandrova, E V; Zaĭtsev, O S; Tenedieva, V D; Potapov, A A; Zakharova, N E; Kravchuk, A D; Oshorov, A V; Sokolova, E Iu; Shukhraĭ, V A; Vorob'ev, Iu V

    2011-01-01

    Changes in plasma noradrenalin (NA) and dopamine (DA) levels were evaluated in the stages of consciousness recovery in patients with severe traumatic brain injury with and without deep brain structure damage. Forty-eight patients (36 men and 12 women), aged from 12 to 56 (31,9±10,9) yeas, were enrolled in the study. Two variants of catecholamine (CA) changes were found: 1) a CA-dissociation that was oppositely directed to NA and DA changes was observed in unconsciousness; 2) a CA-dissociation (unidirectional NA and DA changes) that was observed after the restoration of consciousness. In patients with the damage of two frontal lobes and deep brain structures, CA-association periods were seen in the stage of mental confusion with psychomotor agitation or when the brain stem was damaged. The duration of CA-association was negatively correlated with the velocity, quality of consciousness recovery and outcomes evaluated by the Glasgow scale.

  9. Changes induced by sodium cromoglycate in brain catecholamine turnover in morphine dependent and abstinent mice.

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    San-Martín-Clark, O; Cuéllar, B; De Alba, J; Leza, J C; Lorenzo, P

    1995-04-01

    The effects of sodium cromoglycate (CRO) were studied in relation to the metabolism of brain catecholamines: dopamine (DA) and noradrenaline (NA), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG). CRO was injected SC in control mice, morphine-tolerant mice (tolerance was induced by SC implantation of a 75 mg morphine pellet; CRO was administered on day 4 of addiction) and 30 min before abstinence (withdrawal was induced by SC injection of naloxone (1 mg/kg) on day 4 of addiction). Brain catecholamines and their metabolites were measured using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD), for DA, NA, DOPAC and HVA, and coupled with fluorescence detection for MHPG. The ratios of DOPAC + HVA/DA and MHPG/NA were kept as an index of DA and NA turnovers, respectively. CRO administered 30 min before naloxone-precipitated withdrawal diminished significantly NA levels in frontal cortex. CRO increased DA turnover in striatum and frontal cortex in naive animals and significantly diminished DA levels in frontal cortex and DOPAC levels in frontal cortex and midbrain in morphine-dependent mice. These findings are discussed in relation to the protective effects of CRO on opiate withdrawal and the effects of CRO on locomotor activity.

  10. Brain catecholamines in spontaneously hypertensive and DOCA-salt hypertensive rats.

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    Fujino,Kazuyuki

    1984-08-01

    Full Text Available The concentrations and alpha-methyl-p-tyrosine (alpha-MPT induced disappearance of catecholamines, adrenaline, noradrenaline and dopamine, were measured in selected areas of the brainstem and hypothalamus of spontaneously hypertensive rats (SHR and deoxycorticosterone acetate (DOCA-salt hypertensive rats. The catecholamine levels were measured by a sensitive radioenzymatic assay method combined with microdissection of the rat brain. The adrenaline concentration was higher in the area A1 of young SHR, but not in adult SHR, than in age-matched control rats. Noradrenaline concentrations and the alpha-MPT induced noradrenaline disappearance were less in the rostral part of the nucleus tractus solitarii (NTS and the nucleus hypothalamic anterior of young SHR, and in the rostral part of the NTS of adult SHR. On the other hand in DOCA-salt hypertensive rats, the concentrations of adrenaline and noradrenaline were the same as in control rats in the examined areas. The alpha-MPT induced noradrenaline disappearance was less in the rostral part of the NTS of DOCA-salt hypertensive rats. Dopamine concentrations and the alpha-MPT induced dopamine disappearance were the same in the examined areas of SHR and DOCA-salt hypertensive rats. The results suggest that SHR have a change in adrenergic neural activity in the brainstem and a decrease in noradrenergic neural activity in the brainstem and hypothalamus while DOCA-salt hypertensive rats have a decrease in noradrenergic neural activity in the brainstem. Such changes in brain catecholaminergic neurons may have played an important role in the development of hypertension in these rats.

  11. Increased biogenic catecholamine and metabolite levels in two patients with malignant catatonia

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    Nisijima K

    2013-08-01

    Full Text Available Koichi Nisijima Department of Psychiatry, Jichi Medical University, Tochigi, Japan Abstract: The pathophysiology of malignant catatonia, a rare life-threatening psychiatric syndrome, has not yet been elucidated. This paper reports on two patients with malignant catatonia who showed elevated urinary or plasma catecholamine levels. Patient 1 had high catecholamine and metabolite levels in a 24-hour urine sample, and patient 2 had elevated plasma catecholamine levels. These findings indicate the presence of peripheral sympathetic nervous system hyperactivity in malignant catatonia. Symptoms of autonomic dysfunction, including tachycardia, labile blood pressure, and diaphoresis, are typical features of malignant catatonia and may be related to the increased levels of biogenic amines in these cases. Although the findings in the present study cannot entirely explain the pathophysiology of malignant catatonia, they do indicate that hyperactivity of the sympathetic nervous system may be involved in the pathology of this condition. Keywords: malignant catatonia, catecholamine levels, neuroleptic malignant syndrome

  12. The relationship between catecholamines levels in mother and fetus, and pathogenesis of pregnancy-induced hypertension

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    张为远; 赵艳辉; 殷艳玲

    2003-01-01

    Objective To study the relationship between pregnancy-induced hypertension (PIH) and catecholamine levels.Methods Catecholamines levels in maternal and fetal blood were determined in 116 patients with PIH and 40 normal control subjects using high performance liquid chromatography. The normal control subjects and PIH cases were selected from patients at term pregnancy receiving elective cesarean section. Results Plasma norepinephrine (NE) levels were significantly higher in patients with severe PIH than those in control subjects (P<0.05). Both patients and control subjects had higher NE levels in the umbilical artery blood than in the umbilical vein blood (P<0.05). NE levels in the umbilical artery blood were five times higher than those in the maternal blood.Conclusion The pathogenesis of PIH may relate to catecholamine concentrations in fetus.

  13. Plasma levels of catecholamines and asymmetric dimethylarginine levels as predictive values of mortality among hemodialysis patients

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    Dziedzic Marcin

    2014-06-01

    Full Text Available The aim of the study was to assess plasma concentration of catecholamines and asymmetric dimethyl arginine levels and a possible relationship to predict the mortality rates among hemodialysis patients. The study population comprised 27 subjects, aged 65-70 years. Each patient underwent dialysis thrice a week. Furthermore, the median duration of hemodialysis was 3.5 years. Based on the conducted research, it can be concluded that the concentrations of adrenaline and the level of asymmetric dimethylarginine have predictive value of mortality among hemodialysis patients. Of note, lowering plasma asymmetric dimethylarginine concentration may represent therapeutic target for prevention of progressive renal damage.

  14. Changes in plasma catecholamines levels as preclinical biomarkers in experimental models of Parkinson's disease.

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    Kim, A R; Ugryumov, M V

    2015-01-01

    The goal of this study was to investigate the changes in the concentrations of blood plasma catecholamines as possible biomarkers of Parkinson's disease (PD) in the mouse experimental model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A significant decrease was detected in the levels of dopamine and L-DOPA in the PD preclinical stage model as a result of the catecholamines systemic metabolism disfunction. In the PD early clinical stage models, the level of L-DOPA and dihydroxyphenylacetic acid decreased, which is consistent with the results of blood tests in untreated patients.

  15. Vasopressin modulates the activity of catecholamine containing neurons in specific brain regions.

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    Versteeg, D H; De Kloet, E R; Greidanus, T V; De Wied, D

    1979-01-01

    Following the i.c.v. administration of antivasopressin serum the alpha-MPT-induced disappearance of noradrenaline was decreased in the dorsal septal nucleus, parafascicular nucleus and the rostral part of the nucleus tractus solitarii, whereas that of dopamine was lowered in the caudate nucleus and in the A2 region of the medulla oblongata. In general the effects are opposite to those previously found following the i.c.v. administration of vasopressin. The results support the hypothesis that vasopressin modulates catecholamine neurotransmission in specific brain regions of the rat.

  16. Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine apparently increases brain serotoninergic activity in the rat: no influence of previous chronic immobilization stress.

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    Pol, O; Campmany, L; Armario, A

    1995-09-01

    The functional relationship between brain catecholamines and serotoninergic function was studied in stress-naive and chronically immobilized rats after blockade of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha MpT). The levels of noradrenaline (NA), serotonin, and 5-hydroxyindole acetic acid (5-HIAA) in pons plus medulla, brainstem, hypothalamus, hippocampus, and frontal cortex, and those of 3-methoxy, 4-hydroxyphenile-tileneglicol sulphate (MHPG-SO4) in the hypothalamus were measured by HPLC. Chronic immobilization (IMO) resulted in higher NA levels in pons plus medulla and hypothalamus, the latter area (the only one in which the NA metabolite was determined) also showing slightly elevated MHPG-SO4 levels as compared to stress-naive rats. Chronic IMO did not alter either serotonin or 5-HIAA levels, but acute stress consistently increased 5-HIAA levels in all areas, independently of previous chronic stress. Administration of alpha-MpT drastically reduced NA and increased 5-HIAA levels in all brain regions excepting the frontal cortex. The effect of the drug on serotoninergic function was not altered by previous chronic exposure to IMO. These data suggest that the noradrenergic system appears to exert a tonic inhibitory effect on serotoninergic activity in the brain, with the intensity of the effect depending on the brain area studied. In addition, chronic stress does not appear to alter the functional relationship between noradrenergic and serotoninergic activities, although interactions might exist in more restricted brain areas; this deserves further study.

  17. Features Of Daily Dynamics Of Catecholamine Level In Myocardium Under The Influence Of Low Alcohol Drinks

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    O.I. Kostin

    2009-09-01

    Full Text Available The research goal was to study the features of daily dynamics of adrenaline and noradrenaline content in various parts of myocardium at the rats receiving nonalcoholic and alcohol-containing beer at ordinary light regimen. Substantial increase of level of adrenaline and noradrenaline in all parts of myocardium at the rats received nonalcoholic and spirit-based beer in comparison with the control. At the rats received nonalcoholic beer, authentically higher content of adrenaline and low noradrenaline in myocardium in comparison with animals received alcohol-containing beer was observed. The circadian dynamics of catecholamine level in all parts of heart myocardium was disturbed at animals of both experimental groups in comparison with the control. The revealed disturbances of level of daily catecholamine dynamics in myocardium under the influence of beer, undoubtedly, are bound with negative action of nonalcoholic nature ingredients present in beer. Key words: adrenaline, noradrenaline, myocardium, low alcohol drinks.

  18. Changes in eosinophil and corticosterone levels and catecholamine metabolism during emotionalpainful stress

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    Malyshev, V.V.; Manukhin, B.N.; Petrova, V.A.

    1985-08-01

    The aim of this investigation was to study blood levels of eosinophils, corticosterone (CS), adrenalin, noradrenalin (NA), and dopamine (DA) during the development of the stress reaction, and also to study neuronal uptake and synthesis of catecholamines in the adrenals and heart. In some animal groups, the neuronal uptake of /sup 3/H-NA and the intensity of /sup 3/H-Na and /sup 3/H-DA synthesis from /sup 3/H-tyrosine were investigated by a method described previously, 2 h after the end of induction of emotional-painful stress (EPS). Radioactivity was measured on an SL-30 liquid scintillation counter. A regular relationship was found between changes in blood eosinophil level, the CH concentration, and catecholamine metabolism in the course of EPS.

  19. Disappearance and recovery of catecholamine innervation in brain regions of adult goldfish following 6-hydroxydopamine treatment.

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    Contestabile, A; Friz, T; Caravaggio, M V

    1979-10-01

    The effect of 6-OHDA treatment on catecholamine innervation was studied in the cerebellum, optic tectum and lobus vagi of the goldfish. Catecholamine terminals completely disappeared in less than two weeks after intraventricular injection of 10 microgram 6-OHDA. In periods comprised between 40 days and 4 months after drug injection, catecholamine terminals reappeared to a different degree. The cerebellum showed the highest recovery and, as far as the valvula cerebelli was concerned, also over-innervation. The remarkable power to restore catecholamine innervation led to a distribution of reappearing terminals similar to that of normal animals in the different layers of the three structures examined.

  20. Catecholamines and their enzymes in discrete brain areas of rats after space flight on biosatellites Cosmos.

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    Kvetnansky, R; Culman, J; Serova, L V; Tigranjan, R A; Torda, T; Macho, L

    1983-01-01

    The activity of the catecholaminergic system was measured in the hypothalamus of rats which had experienced an 18.5-19.5-day-long stay in the state of weightlessness during space flights on board Soviet biosatellites of the type Cosmos. In the first two experiments, Cosmos 782 and 936, the concentration of norepinephrine and the activities of synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase and of the degrading enzyme monoamine oxidase were measured in the total hypothalamus. None of the given parameters was changed after space flight. In the light of the changes of these parameters recorded after exposure to acute stress on Earth, this finding indicates that long-term state of weightlessness does not represent an intensive stressogenic stimulus for the system studied. In the space experiment Cosmos 1129, the concentration of norepinephrine, epinephrine, and dopamine was studied in isolated nuclei of the hypothalamus of rats within 6-10 hr following return from space. Norepinephrine was found to be significantly reduced in the arcuate nucleus, median eminence and periventricular nucleus, epinephrine in the median eminence, periventricular and suprachiasmatic nuclei, whereas dopamine was not significantly changed after space flight. The decreased catecholamine levels found in some hypothalamic nuclei of rats which had undergone space flight indicate that no chronic intensive stressor could have acted during the flight, otherwise the catecholamine concentration would have been increased in the nuclei. The decreased levels must have been induced by the effect of a stressogenic factor acting for a short time only, and that either during the landing maneuver or immediately after landing. Thus long-term exposure of the organism to the state of weightlessness does not represent a stressogenic stimulus for the catecholaminergic system in the hypothalamus, which is one of the regulators of the activation of neuroendocrine reactions under stress.

  1. Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction.

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    Kim, Nahyun; Hughes, Tonda L; Park, Chang G; Quinn, Laurie; Kong, In Deok

    2016-03-01

    The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents.

  2. Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs.

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    Poncet, M. F.; Damase-Michel, C.; Tavernier, G.; Tran, M. A.; Berlan, M.; Montastruc, J. L.; Montastruc, P.

    1992-01-01

    1. Plasma levels of noradrenaline (NA) and neuropeptide Y (NPY) were evaluated in two experimental models associated with an increase in sympathetic tone: conscious dogs which were subject to either sinoaortic denervation or acute administration of the alpha 2-adrenoceptor antagonist yohimbine. 2. Dogs that had undergone sinoaortic denervation exhibited a two fold increase in plasma NA without any change in NPY levels. 3. Yohimbine (0.05 mg kg-1 i.v. as a bolus) produced similar effects. A higher dose of yohimbine (0.5 mg kg-1 i.v.) increased both plasma NA (7 fold) and NPY (6.5 fold) levels. 4. The present results indicate that changes in plasma catecholamines and NPY are not always concomitant. They suggest that the simultaneous release of NA and NPY is only observed under in vivo conditions for a marked increase in sympathetic tone. PMID:1596679

  3. Effects of ovarian stimulation on blood pressure and plasma catecholamine levels.

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    Tollan, A; Oian, P; Kjeldsen, S E; Holst, N; Eide, I

    1993-07-01

    Effects of ovarian stimulation for in vitro fertilization on blood pressure and plasma catecholamine levels were studied in 10 women. The examinations were carried out before hormonal treatment with human menopausal gonadotropin (day three of the menstrual cycle, mean serum oestradiol concentration 0.2 nmol l-1, and on the day after ovulation induction with human chorionic gonadotropin (cycle days 10-12, mean serum oestradiol concentration 7.4 nmol l-1). Systolic and diastolic blood pressures (mean +/- SD) decreased 6.7 +/- 8.6 mm Hg, p = 0.049, and 5.3 +/- 4.7 mm Hg, p = 0.009, respectively), and venous plasma noradrenaline increased (42 +/- 44 pg ml-1, p = 0.02) during ovarian stimulation. No significant change was observed in either arterial noradrenaline, arterial adrenaline or venous adrenaline. After stimulation a positive correlation was observed between systolic blood pressure and arterial adrenaline (r = 0.73, p = 0.027), and between systolic blood pressure and the arterial-venous difference for adrenaline (r = 0.81, p = 0.007). The increased venous noradrenaline levels may be a reflex-mediated activation of the sympathetic nervous tone due to a decrease in blood pressure, or may indicate reduced neuronal re-uptake of released noradrenaline. The mechanisms behind the strong correlation between adrenaline and blood pressure are unclear, but may be induced by the supraphysiological oestradiol levels. Thus, adrenaline seems to be more important for blood pressure control in this particular setting.

  4. Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.

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    Ueda, N; Yoshimura, R; Shinkai, K; Nakamura, J

    2002-09-01

    We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

  5. [A case of adrenal pheochromocytoma with normotention and normal levels of urinary excretion of catecholamines].

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    Motomura, K; Okano, J; Sasaki, I; Ogihara, T; Ishii, H; Tanaka, A; Ibayashi, H; Abe, Y; Kuramoto, H; Yanase, T

    1994-09-01

    A 62-year-old man was admitted to our hospital for further examination of right adrenal mass accidentally pointed out by ultrasonogram. He had no symptoms and no physiological abnormalities. Endcrinological examinations revealed normal adrenocortical function, excluding the possibility of functioning adrenocortical adenoma. Pheochromocytoma seemed to be also unlikely since 24-hr urinary excretion of catecholamines were within normal limits. The tumor was surgically removed and histopathologically diagnosed as pheochromocytoma. This case of adrenal incidentaloma is unique in that little sign of pheochromocytoma was presented before operation. The reasons were discussed especially in respect of tissue contents of catecholamines and opioid peptide in comparison with other cases with pheochromocytoma we had experienced.

  6. Possible interaction of the adrenal-gonadal systems on brain catecholamines of adult male rats.

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    Leret, M L; Tranque, P; González, I; Calvo, J C

    1987-01-01

    Studies from this laboratory showed that gonadectomy (GDX) alters biogenic amines concentrations in diencephalon during the first 40 days. While the GDX females maintain the differences at day 60, the differences are eliminated in males at that time. In the present work, we have studied in three cerebral regions the adrenal involvement in the mechanism responsible for this normalization of catecholamine concentration in long-term castrated adult male rats. A hypersecretion of adrenal steroids seems to compensate for the lack of gonadal effect when the orchidectomized rats reach adulthood only for diencephalic dopamine.

  7. Association of increased circulating catecholamine and glucocorticoid levels with risk of psychological problems in oral neoplasm patients.

    Directory of Open Access Journals (Sweden)

    Huixu Xie

    Full Text Available Noradrenergic pathways and glucocorticoid-mediated signal pathways have been implicated in the growth and progression of oral cancer. Patients with oral neoplasms can have high psychological distress levels, but the effects of stress-related hormones on oral neoplasm growth are unknown.We have investigated the relationships between pre-surgical measurements of psychological problems with Symptom Checklist-90-revised Inventory (SCL90-R, tumor histology, circulating blood catecholamine and glucocorticoid levels among 75 oral neoplasm patients, including 40 oral cancer patients and 35 benign oral tumor patients.The results showed that most dimension scores of SCL90-R did not show a significant difference between the two groups except depression (p = 0.0201 and obsessive-compulsion (p = 0.0093, with the scores for these symptoms being higher among oral cancer group versus the benign oral tumor group. The differences of total score, average score and other monomial factor scores were not statistically significant. The mean concentrations of catecholamine and glucocorticoid in peripheral blood of the oral cancer group were higher than those in benign oral tumor group (p<0.01. We also examined whether associations observed between biobehavioral measures and circulating blood catecholamine and glucocorticoid levels extended to other compartments in the oral cancer group.These findings suggest that stress hormones may affect oral cancer behavior by influencing the tumor micro-environment though the circulating blood.

  8. Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin.

    Science.gov (United States)

    Kawa, Lizan; Arborelius, Ulf P; Yoshitake, Takashi; Kehr, Jan; Hökfelt, Tomas; Risling, Mårten; Agoston, Denes

    2015-08-15

    Exposure to improvised explosive devices can result in a unique form of traumatic brain injury--blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.

  9. Acupuncture inhibits the decrease in brain catecholamine contents and the impairment of passive avoidance task in ovariectomized mice.

    Science.gov (United States)

    Toriizuka, K; Okumura, M; Iijima, K; Haruyama, K; Cyong, J C

    1999-01-01

    The effects of acupuncture on the disorders elicited by abnormalities of endocrine system were investigated in ovariectomized mice. Female mice (strain; C57BL/6) were ovariectomized (OVX) and acupuncture points, Shenshu ([Japanese pictograph see text] : BL23) on both side of the back were continuously stimulated by subcutaneous needles for 20 days. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for catecholamine contents by high performance liquid chromatography with electro chemical detector (ECD-HPLC). The mitogenic activities of splenic lymphocytes were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTS) assay and alkaline phosphatase (ALP) assay. Furthermore, the effects of needle stimulation on learning and memory ability were studied by the step-through type passive avoidance test. Norepinephrine and dopamine contents in the frontoparietal cerebral cortex, ventral hippocampus and olfactory bulb were decreased in the OVX group, and both MTS activity and ALP activity were decreased 20 days after ovariectomy. The mean latent period was also shortened in the passive avoidance test in the OVX group. However, applying needle stimulation increased norepinephrine and dopamine contents in the brain regions, and enhanced mitogenic activities of splenic lymphocytes. The stimulation also improved memory-related behavior. It was concluded from this study that after mice were stimulated by subcutaneous needle insertion, overall changes were observed in central nervous system (including retention of memory) and immune functions. The study suggests that acupuncture improves the memory loss and decrease of immune responses accompanying aging and/or menopause, and the that it may have an important role in medical care for the elderly.

  10. Plasma and urine catecholamine levels in cosmonauts during long-term stay on Space Station Salyut-7

    Science.gov (United States)

    Kvetn̆anský, R.; Davydova, N. A.; Noskov, V. B.; Vigas̆, M.; Popova, I. A.; Us̆akov, A. C.; Macho, L.; Grigoriev, A. I.

    The activity of the sympathetic adrenal system in cosmonauts exposed to a stay in space lasting for about half a year has so far been studied only by measuring catecholamine levels in plasma and urine samples taken before space flight and after landing. The device "Plasma 01", specially designed for collecting and processing venous blood from subjects during space flight on board the station Salyut-7 rendered it possible for the first time to collect and freeze samples of blood from cosmonauts in the course of a long-term 237-day space flight. A physician-cosmonaut collected samples of blood and urine from two cosmonauts over the period of days 217-219 of their stay in space. The samples were transported to Earth frozen. As indicators of the sympathetic adrenal system activity, plasma and urine concentrations of epinephrine and norepinephrine as well as urine levels of the catecholamine metabolites metanephrine, normetanephrine, and vanillylmandelic acid were determined before, during and after space flight. On days 217-219 of space flight plasma epinephrine and norepinephrine levels were slightly increased, yet not substantially different from normal. During stress situations plasma norepinephrine and epinephrine levels usually exhibit a manifold increase. On days 217-219 of space flight norepinephrine and epinephrine levels in urine were comparable with pre-flight values and the levels of their metabolites were even significantly decreased. All the parameters studied, particularly plasma norepinephrine as well as urine norepinephrine, normetanephrine, and vanillylmandelic acid, reached the highest values 8 days after landing. The results obtained suggest that, in the period of days 217-219 of the cosmonauts' stay in space in the state of weightlessness, the sympathetic adrenal system is either not activated at all or there is but a slight activation induced by specific activities of the cosmonauts, whereas in the process of re-adaptation after space flight on

  11. Plasma levels of free metanephrines and 3-methoxytyramine indicate a higher number of biochemically active HNPGL than 24-h urinary excretion rates of catecholamines and metabolites

    NARCIS (Netherlands)

    Corssmit, E. P. M.; de Jong, W. H. A.; Brookman, D.; Kema, I. P.; Romijn, J. A.; van Duinen, N.

    2013-01-01

    Context: A substantial number of patients with head and neck paragangliomas (HNPGLs) have biochemically active tumors, evidenced by increased urinary excretion of catecholamines and metabolites, including 3-methoxytyramine (3MT). It is unclear whether plasma levels of these parameters are more sensi

  12. A potential benefit of albinism in Astyanax cavefish: downregulation of the oca2 gene increases tyrosine and catecholamine levels as an alternative to melanin synthesis.

    Science.gov (United States)

    Bilandžija, Helena; Ma, Li; Parkhurst, Amy; Jeffery, William R

    2013-01-01

    Albinism, the loss of melanin pigmentation, has evolved in a diverse variety of cave animals but the responsible evolutionary mechanisms are unknown. In Astyanax mexicanus, which has a pigmented surface dwelling form (surface fish) and several albino cave-dwelling forms (cavefish), albinism is caused by loss of function mutations in the oca2 gene, which operates during the first step of the melanin synthesis pathway. In addition to albinism, cavefish have evolved differences in behavior, including feeding and sleep, which are under the control of the catecholamine system. The catecholamine and melanin synthesis pathways diverge after beginning with the same substrate, L-tyrosine. Here we describe a novel relationship between the catecholamine and melanin synthesis pathways in Astyanax. Our results show significant increases in L-tyrosine, dopamine, and norepinephrine in pre-feeding larvae and adult brains of Pachón cavefish relative to surface fish. In addition, norepinephrine is elevated in cavefish adult kidneys, which contain the teleost homologs of catecholamine synthesizing adrenal cells. We further show that the oca2 gene is expressed during surface fish development but is downregulated in cavefish embryos. A key finding is that knockdown of oca2 expression in surface fish embryos delays the development of pigmented melanophores and simultaneously increases L-tyrosine and dopamine. We conclude that a potential evolutionary benefit of albinism in Astyanax cavefish may be to provide surplus L-tyrosine as a precursor for the elevated catecholamine synthesis pathway, which could be important for adaptation to the challenging cave environment.

  13. A potential benefit of albinism in Astyanax cavefish: downregulation of the oca2 gene increases tyrosine and catecholamine levels as an alternative to melanin synthesis.

    Directory of Open Access Journals (Sweden)

    Helena Bilandžija

    Full Text Available Albinism, the loss of melanin pigmentation, has evolved in a diverse variety of cave animals but the responsible evolutionary mechanisms are unknown. In Astyanax mexicanus, which has a pigmented surface dwelling form (surface fish and several albino cave-dwelling forms (cavefish, albinism is caused by loss of function mutations in the oca2 gene, which operates during the first step of the melanin synthesis pathway. In addition to albinism, cavefish have evolved differences in behavior, including feeding and sleep, which are under the control of the catecholamine system. The catecholamine and melanin synthesis pathways diverge after beginning with the same substrate, L-tyrosine. Here we describe a novel relationship between the catecholamine and melanin synthesis pathways in Astyanax. Our results show significant increases in L-tyrosine, dopamine, and norepinephrine in pre-feeding larvae and adult brains of Pachón cavefish relative to surface fish. In addition, norepinephrine is elevated in cavefish adult kidneys, which contain the teleost homologs of catecholamine synthesizing adrenal cells. We further show that the oca2 gene is expressed during surface fish development but is downregulated in cavefish embryos. A key finding is that knockdown of oca2 expression in surface fish embryos delays the development of pigmented melanophores and simultaneously increases L-tyrosine and dopamine. We conclude that a potential evolutionary benefit of albinism in Astyanax cavefish may be to provide surplus L-tyrosine as a precursor for the elevated catecholamine synthesis pathway, which could be important for adaptation to the challenging cave environment.

  14. Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Albino Villegas-Bastida

    2014-01-01

    Full Text Available Electrical vagus nerve (VN stimulation during sepsis attenuates tumor necrosis factor (TNF production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36 on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP. The septic rats were subsequently treated with EA-ST36 (CLP+ST36, and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P<0.05, and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms.

  15. Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms

    Science.gov (United States)

    Villegas-Bastida, Albino; Torres-Rosas, Rafael; Arriaga-Pizano, Lourdes Andrea; Flores-Estrada, Javier; Gustavo-Acosta, Altamirano; Moreno-Eutimio, Mario Adan

    2014-01-01

    Electrical vagus nerve (VN) stimulation during sepsis attenuates tumor necrosis factor (TNF) production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36) on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP). The septic rats were subsequently treated with EA-ST36 (CLP+ST36), and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P < 0.05), and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms. PMID:25057275

  16. Effects of α-endorphin, β-endorphin and (des-tyr1)-γ-endorphin on α-MPT-induced catecholamine disappearance in discrete regions of the rat brain

    NARCIS (Netherlands)

    Versteeg, D.H.G.; Kloet, E.R. de; Wied, D. de

    1979-01-01

    Summary Following the intracerebroventricular administration of α-endorphin, β-endorphin and (des-tyrosine1)-γ-endorphin in a dose of 100 ng, the α-MPT-induced catecholamine disappearance was found to be altered in discrete regions of the rat brain. In the regions in which α-endorphin exerted an eff

  17. Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis

    DEFF Research Database (Denmark)

    Tage-Jensen, U; Henriksen, Jens Henrik; Christensen, E

    1988-01-01

    clinical and biochemical variables and survival. Forty-seven (58%) of the patients died during the follow-up period. Univariate analysis showed that plasma noradrenaline and adrenaline concentrations, portal pressure, indocyanine green clearance, serum sodium, bilirubin, and albumin concentrations......, and the presence of ascites or cardiovascular disease were of significant prognostic value. In a multivariate analysis (Cox regression model), plasma noradrenaline concentration, portal pressure, serum bilirubin concentration, and the presence of ascites and cardiovascular disease remained significant independent...... predictors of survival. The results suggest that determination of the circulating level of noradrenaline and portal pressure may add to the prognostic information on survival obtained from routine tests. Thus, the activity of the sympathetic nervous system may indicate the severity of cirrhosis with respect...

  18. Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis

    DEFF Research Database (Denmark)

    Tage-Jensen, U; Henriksen, Jens Henrik Sahl; Christensen, E

    1988-01-01

    clinical and biochemical variables and survival. Forty-seven (58%) of the patients died during the follow-up period. Univariate analysis showed that plasma noradrenaline and adrenaline concentrations, portal pressure, indocyanine green clearance, serum sodium, bilirubin, and albumin concentrations......, and the presence of ascites or cardiovascular disease were of significant prognostic value. In a multivariate analysis (Cox regression model), plasma noradrenaline concentration, portal pressure, serum bilirubin concentration, and the presence of ascites and cardiovascular disease remained significant independent...... predictors of survival. The results suggest that determination of the circulating level of noradrenaline and portal pressure may add to the prognostic information on survival obtained from routine tests. Thus, the activity of the sympathetic nervous system may indicate the severity of cirrhosis with respect...

  19. Effects of music therapy on autonomic nervous system activity, incidence of heart failure events, and plasma cytokine and catecholamine levels in elderly patients with cerebrovascular disease and dementia.

    Science.gov (United States)

    Okada, Kaoru; Kurita, Akira; Takase, Bonpei; Otsuka, Toshiaki; Kodani, Eitaro; Kusama, Yoshiki; Atarashi, Hirotsugu; Mizuno, Kyoichi

    2009-01-01

    Music therapy (MT) has been used in geriatric nursing hospitals, but there has been no extensive research into whether it actually has beneficial effects on elderly patients with cerebrovascular disease (CVD) and dementia. We investigated the effects of MT on the autonomic nervous system and plasma cytokine and catecholamine levels in elderly patients with CVD and dementia, since these are related to aging and chronic geriatric disease. We also investigated the effects of MT on congestive heart failure (CHF) events.Eighty-seven patients with pre-existing CVD were enrolled in the study. We assigned patients into an MT group (n = 55) and non-MT group (n = 32). The MT group received MT at least once per week for 45 minutes over 10 times. Cardiac autonomic activity was assessed by heart rate variability (HRV). We measured plasma cytokine and catecholamine levels in both the MT group and non-MT group. We compared the incidence of CHF events between these two groups. In the MT group, rMSSD, pNN50, and HF were significantly increased by MT, whereas LF/HF was slightly decreased. In the non-MT group, there were no significant changes in any HRV parameters. Among cytokines, plasma interleukin-6 (IL-6) in the MT group was significantly lower than those in the non-MT group. Plasma adrenaline and noradrenaline levels were significantly lower in the MT group than in the non-MT group. CHF events were less frequent in the MT group than in the non-MT group (P < 0.05). These findings suggest that MT enhanced parasympathetic activities and decreased CHF by reducing plasma cytokine and catecholamine levels.

  20. Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: Effect of L-DOPA treatment and changes in levodopa-induced dyskinesia.

    Science.gov (United States)

    Andersen, A D; Blaabjerg, M; Binzer, M; Kamal, A; Thagesen, H; Kjaer, T W; Stenager, E; Gramsbergen, J B

    2017-02-28

    Levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to L-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily L-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID (PD-LID, n=8)) as compared to non-dyskinetic PD patients receiving L-DOPA (PD-L, n=6), or not receiving L-DOPA (PD-N, n=7) as well as non-PD controls (n=16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 hours after oral intake of L-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (1) decreased levels of dihydroxyphenylacetic acid and homovanillic acid in PD patients not receiving L-DOPA (2) higher DA levels in LID as compared to controls (3) higher DA/L-DOPA and lower DOPAC/DA ratio's in LID as compared to PDL and (4) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of L-DOPA-treated PD patients may help identify patients at risk of developing LID. This article is protected by copyright. All rights reserved.

  1. Catecholamine blood test

    Science.gov (United States)

    Norepinephrine -- blood; Epinephrine -- blood; Adrenalin -- blood; Dopamine -- blood ... A blood sample is needed. ... the test. This is especially true if both blood and urine catecholamines are to be measured. You ...

  2. Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

    Science.gov (United States)

    Virgolini, Miriam B; Chen, Kevin; Weston, Doug D; Bauter, Mark R; Cory-Slechta, Deborah A

    2005-10-01

    Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.

  3. [Mechanism of the preventing of endotracheal intubation response with esmolol-the relationship between the plasma catecholamine level and bispectral index].

    Science.gov (United States)

    Jin, Yun yu; Yang, Lan; Zhu, Sai nan; Pan, Zhen Yu; Bai, Yu; Fan, Zhi yi

    2008-04-01

    To observe the relationship between the level of catecholamine in plasma with bispectral index during endotracheal intubation with propofol anesthesia in order to investigate the mechanism of the preventing of endotracheal intubation response with esmolol. Thirty patients were randomly allocated into two groups: control group (n=15) and esmolol group (n=15). The patients received esmolol 1amg/kg followed by 250 microg/(kgdmin) in esmolol group and saline in control group. Two minutes later, the patients received propofol 2amg/kg for induction. Bispectral index (BIS), systolic pressure (SP), diostolic pressure (DP), and heart rate (HR) were measured before endotracheal intubation and 3amin after intubation, at the same time 8a mL arteral blood was taken for the measurement of the concentrations of norephinephrine(NE) and ephinephrine(E) in plasma. The level of BIS(63.53+/-3.11), NE(2.016+/-0.681)and E(0.578+/-0.072)in control group 3 min after endotracheal intubation were increased significantly than those before intubation (Pendotracheal intubation . There were significant differences in the concentrations of NE(2.016+/-0.681)and E(0.578+/-0.072) in plasma 3 min after intubation between the two groups (Pintubation between the two groups(Pintubation than those before intubation (Pintubation than those before intubation. Esmolol can reduce the plasma concentrations of NE and E through preventing periopheal sympathetic nerve response to intubation and can reduce BIS arousal reactions after endotracheal intubation.

  4. Cerebrospinal fluid levels of catecholamine metabolites in Parkinson’s disease and L-DOPA-induced dyskinesia

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon;

    Levodopa (L-DOPA) is effective in the symptomatic treatment of Parkinson’s disease (PD), but chronic use is associated with L-DOPA-induced dyskinesia (LID). In the 6-hydroxydopamine rat model of PD, L-DOPA treatment increases dopamine, its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC...... fasting and 1 hour after intake of medication. Results and conclusion: PD patients receiving levodopa had 10-20 fold higher L-DOPA levels and about 100 fold higher levels of 3-OMD than age-matched controls or PD not receiving L-DOPA. DOPAC levels were not different among controls and subgroups of PD. HVA...... levels were significantly lower in non-DOPA-treated PD. Ratios of DOPAC/DOPA or HVA/DOPA were much lower in levodopa-treated patients, not distinguishing dyskinetic (N=6) from non-dyskinetic PD patients (N=5). More patients need to be included. Tryptophan/kynurenine metabolites will be analysed using LC...

  5. Real-time monitoring of electrically evoked catecholamine signals in the songbird striatum using in vivo fast-scan cyclic voltammetry.

    Science.gov (United States)

    Smith, Amanda R; Garris, Paul A; Casto, Joseph M

    2015-01-01

    Fast-scan cyclic voltammetry is a powerful technique for monitoring rapid changes in extracellular neurotransmitter levels in the brain. In vivo fast-scan cyclic voltammetry has been used extensively in mammalian models to characterize dopamine signals in both anesthetized and awake preparations, but has yet to be applied to a non-mammalian vertebrate. The goal of this study was to establish in vivo fast-scan cyclic voltammetry in a songbird, the European starling, to facilitate real-time measurements of extracellular catecholamine levels in the avian striatum. In urethane-anesthetized starlings, changes in catecholamine levels were evoked by electrical stimulation of the ventral tegmental area and measured at carbon-fiber microelectrodes positioned in the medial and lateral striata. Catecholamines were elicited by different stimulations, including trains related to phasic dopamine signaling in the rat, and were analyzed to quantify presynaptic mechanisms governing exocytotic release and neuronal uptake. Evoked extracellular catecholamine dynamics, maximal amplitude of the evoked catecholamine signal, and parameters for catecholamine release and uptake did not differ between striatal regions and were similar to those determined for dopamine in the rat dorsomedial striatum under similar conditions. Chemical identification of measured catecholamine by its voltammogram was consistent with the presence of both dopamine and norepinephrine in striatal tissue content. However, the high ratio of dopamine to norepinephrine in tissue content and the greater sensitivity of the carbon-fiber microelectrode to dopamine compared to norepinephrine favored the measurement of dopamine. Thus, converging evidence suggests that dopamine was the predominate analyte of the electrically evoked catecholamine signal measured in the striatum by fast-scan cyclic voltammetry. Overall, comparisons between the characteristics of these evoked signals suggested a similar presynaptic regulation of

  6. Influence of Dermanyssus gallinae (poultry red mite) invasion on the plasma levels of corticosterone, catecholamines and proteins in layer hens.

    Science.gov (United States)

    Kowalski, A; Sokół, R

    2009-01-01

    The results of studies conducted in 2006 revealed that mass red mite (Dermanyssus gallinae) invasions cause somatic stress which may be responsible for the pathophysiological mechanism of decreased egg production, lower humoral immunity and higher mortality in layer hens. The aim of this study was to validate the above research results, to investigate whether in addition to somatic stress, red mite invasions cause psychogenic stress due to the activation of the sympatho-adrenomedullar system, and to determine the level of stress resulting from red mite infestations in comparison with a short, 1.5 h period of acute immobilisation stress. The study investigated 36 HY-Line Brown layer hens divided into three groups: a non-infested control group, an experimental group infested with red mites and a non-infested experimental group subjected to acute immobilisation stress for 1.5 h. Blood samples were taken from all hens for the determination of the levels of corticosterone, adrenaline, noradrenaline, albumin, and alpha-, beta- and gamma-globulins. The results validated the previous reports on the occurrence of somatic stress and on a significant decrease in y-globulin levels (p < or = 0.01) in the group of birds infested with red mites, in comparison with the control group. Adrenaline levels in infested hens were indicative of psychogenic stress. Based on a comparison of hormonal indicators in all hen groups, the level of somatic stress resulting from red mite infestation can be classified as moderate, while the level of psychogenic stress can be interpreted as high. A significant drop in y-globulin levels in the blood of birds infested with red mites also shows that the invasion induces chronic stress which lowers the humoral immunity of hens.

  7. Selective ablation of dopamine β-hydroxylase neurons in the brain by immunotoxin-mediated neuronal targeting: new insights into brain catecholaminergic circuitry and catecholamine-related diseases.

    Science.gov (United States)

    Itoi, Keiichi; Ohara, Shinji; Kobayashi, Kazuto

    2013-01-01

    The locus coeruleus (LC) has been implicated in a variety of physiological functions including sleep/wakefulness, cognition/memory, stress/emotion, and pain. Marked loss of LC-noradrenergic (NAergic) neurons is observed in autopsy specimens of patients with Alzheimer's disease and Parkinson's disease (PD), and part of the clinical symptoms of these diseases may be related to dysfunction of the LC. Neurotoxins have been utilized to ablate LC-NAergic neurons in experimental animals for elucidating the pathophysiological implication of the loss of LC, but there are methodological drawbacks in previously utilized methods. We employed immunotoxin-mediated neuronal targeting to overcome these problems. Following complete disruption of the LC-NAergic neurons by immunotoxin, mice showed behavioral changes, which resembled the nonmotor symptoms of PD. The LC-NAergic neurons did not regenerate following ablation, so the immunotoxin-mediated neuronal targeting may be useful especially for studying the long-term effects of the loss of LC-NAergic neurons on brain functions. © 2013 Elsevier Inc. All rights reserved.

  8. Pyrilamine inhibits nicotine-induced catecholamine secretion.

    Science.gov (United States)

    Kim, Dong-Chan; Yun, So Jeong; Park, Yong-Soo; Jun, Dong-Jae; Kim, Dongjin; Jiten Singh, N; Kim, Sanguk; Kim, Kyong-Tai

    2014-07-01

    Function of nicotine, which induces activation of all parts of the body including our brain, has been receiving much attention for a long period of time and also been actively studied by researchers for its pharmacological actions in the central nervous system. The modulation of nicotine concentration and the inhibition of nicotine binding on target receptors in the brain are the key factors for smoking addiction therapy. In previous studies showed that influx of nicotine at the blood-brain barrier was through the pyrilamine-sensitive organic cation transporters. But the direct interacting mechanism of pyrilamine on the nicotine binding target receptors has not yet been clarified. The aim of the present study is to investigate the direct binding mechanisms of a pyrilamine on the nicotinic acetylcholine receptors (nAChRs). We found that pyrilamine shares the same ligand binding pocket of nicotine (NCT) on nAChRs but interacts with more amino acid residues than NCT does. The extended part of pyrilamine interacts with additional residues in the ligand binding pocket of nAChRs which are located nearby the entrance of the binding pocket. The catecholamine (CA) secretion induced by nAChR agonist (NCT') was significantly inhibited by the pyrilamine pretreatment. Real time carbon-fiber amperometry confirmed the inhibition of the NCT'-induced exocytosis by pyrilamine in a single cell level. We also found that pyrilamine inhibited the NCT'-induced [Ca(2+)]i. In contrast, pyrilamine did not affect the increase in calcium induced by high K(+). Overall, these data suggest that pyrilamine directly docks into the ligand binding site of nAChRs and specifically inhibits the nAChR-mediated effects thereby causing inhibition of CA secretion. Therefore, pyrilamine may play an important role to explore new treatments to aid smoking cessation.

  9. A Fall in Plasma Free Fatty Acid (FFA) Level Activates the Hypothalamic-Pituitary-Adrenal Axis Independent of Plasma Glucose: Evidence for Brain Sensing of Circulating FFA

    Science.gov (United States)

    Oh, Young Taek; Oh, Ki-Sook; Kang, Insug

    2012-01-01

    The brain responds to a fall in blood glucose by activating neuroendocrine mechanisms for its restoration. It is unclear whether the brain also responds to a fall in plasma free fatty acids (FFA) to activate mechanisms for its restoration. We examined whether lowering plasma FFA increases plasma corticosterone or catecholamine levels and, if so, whether the brain is involved in these responses. Plasma FFA levels were lowered in rats with three independent antilipolytic agents: nicotinic acid (NA), insulin, and the A1 adenosine receptor agonist SDZ WAG 994 with plasma glucose clamped at basal levels. Lowering plasma FFA with these agents all increased plasma corticosterone, but not catecholamine, within 1 h, accompanied by increases in plasma ACTH. These increases in ACTH or corticosterone were abolished when falls in plasma FFA were prevented by Intralipid during NA or insulin infusion. In addition, the NA-induced increases in plasma ACTH were completely prevented by administration of SSR149415, an arginine vasopressin receptor antagonist, demonstrating that the hypothalamus is involved in these responses. Taken together, the present data suggest that the brain may sense a fall in plasma FFA levels and activate the hypothalamic-pituitary-adrenal axis to increase plasma ACTH and corticosterone, which would help restore FFA levels. Thus, the brain may be involved in the sensing and control of circulating FFA levels. PMID:22669895

  10. Effects of their nutrient precursors on the synthesis and release of serotonin, the catecholamines, and acetylcholine - Implications for behavioral disorders

    Science.gov (United States)

    Wurtman, Richard J.

    1988-01-01

    Authentic foods affect brain serotonin synthesis by modifying brain tryptophan levels, carbohydrates increasing and proteins decreasing these levels. The carbohydrate-induced rise in brain serotonin tends to diminish the likelihood that one carbohydrate-rich, protein-poor meal or snack will be followed by another. This mechanism is apparently disturbed in carbohydrate-craving obesity, which may explain why this syndrome responds well to d-fenfluramine, a serotoninergic drug. Pure nutrients like tyrosine or choline can also affect the rates at which their neurotransmitter products, the catecholamines and acetylcholine, are synthesized in and released from nerve terminals, suggesting that these compounds may find uses as drugs.

  11. Effects of their nutrient precursors on the synthesis and release of serotonin, the catecholamines, and acetylcholine - Implications for behavioral disorders

    Science.gov (United States)

    Wurtman, Richard J.

    1988-01-01

    Authentic foods affect brain serotonin synthesis by modifying brain tryptophan levels, carbohydrates increasing and proteins decreasing these levels. The carbohydrate-induced rise in brain serotonin tends to diminish the likelihood that one carbohydrate-rich, protein-poor meal or snack will be followed by another. This mechanism is apparently disturbed in carbohydrate-craving obesity, which may explain why this syndrome responds well to d-fenfluramine, a serotoninergic drug. Pure nutrients like tyrosine or choline can also affect the rates at which their neurotransmitter products, the catecholamines and acetylcholine, are synthesized in and released from nerve terminals, suggesting that these compounds may find uses as drugs.

  12. Prefrontal /accumbal catecholamine system processes high motivational salience.

    Directory of Open Access Journals (Sweden)

    Stefano ePuglisi-Allegra

    2012-06-01

    Full Text Available Motivational salience regulates the strength of goal seeking, the amount of risk taken, and the energy invested from mild to extreme. Highly motivational experiences promote highly persistent memories. Although this phenomenon is adaptive in normal conditions, experiences with extremely high levels of motivational salience can promote development of memories that can be re-experienced intrusively for long time resulting in maladaptive outcomes.Neural mechanisms mediating motivational salience attribution are, therefore, very important for individual and species survival and for well-being. However, these neural mechanisms could be implicated in attribution of abnormal motivational salience to different stimuli leading to maladaptive compulsive seeking or avoidance. We have offered the first evidence that prefrontal cortical norepinephrine transmission is a necessary condition for motivational salience attribution to highly salient stimuli, through modulation of dopamine in the nucleus accumbens, a brain area involved in all motivated behaviors. Moreover, we have shown that prefrontal-accumbal catecholamine system determines approach or avoidance responses to both reward- and aversion-related stimuli only when the salience of the unconditioned stimulus is high enough to induce sustained catecholamine activation, thus affirming that this system processes motivational salience attribution selectively to highly salient events.

  13. Catecholamines and diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1995-01-01

    In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors...

  14. Regional brain catecholamine levels and the development of hypertension in the spontaneously hypertensive rat: the effect of 6-hydroxydopamine

    NARCIS (Netherlands)

    Jong, Wybren de; Buuse, M. van den; Kloet, E.R. de; Versteeg, D.H.G.

    1984-01-01

    To investigate the role of central catecholaminergic pathways in the development of hypertension in the spontaneously hypertensive rat (SHR) the effects of intracerebroventricular (i.c.v.) injections of 6-hydroxydopamine (6-OHDA) were compared with those of local injections near the main ascending n

  15. Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks

    Directory of Open Access Journals (Sweden)

    Francisco eAboitiz

    2014-03-01

    Full Text Available A cardinal symptom of Attenion Deficit and Hyperactivity Disorder (ADHD is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the Default Mode Network (DMN. Related networks are the ventral attentional network (VAN involved in attentional shifting, and the salience network (SN related to task expectancy. Here we discuss the tonic-phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produce an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits.

  16. Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks

    Science.gov (United States)

    Aboitiz, Francisco; Ossandón, Tomás; Zamorano, Francisco; Palma, Bárbara; Carrasco, Ximena

    2014-01-01

    A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic–phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits. PMID:24723897

  17. The role of BDNF, leptin, and catecholamines in reward learning in bulimia nervosa.

    Science.gov (United States)

    Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Eckert, Anne; Lang, Undine; Hasler, Gregor

    2014-12-07

    A relationship between bulimia nervosa and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted bulimia nervosa and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 hour after a standardized breakfast. AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (P=.05). Across conditions, plasma brain derived neurotrophic factor levels were higher in remitted bulimia nervosa subjects compared with controls (diagnosis effect; P=.001). Plasma BDNF and leptin levels were higher in the morning before compared with after a standardized breakfast across groups and conditions (time effect; Pbulimia nervosa and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both remitted bulimia nervosa and controls. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  18. Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation.

    LENUS (Irish Health Repository)

    Noori, S

    2014-08-14

    Objective:We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation.Study Design:A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was >15 μg kg(-1)min(-1). Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension).Result:Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration.Conclusion:We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.Journal of Perinatology advance online publication, 14 August 2014; doi:10.1038\\/jp.2014.151.

  19. Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma

    NARCIS (Netherlands)

    Eisenhofer, G.; Pacak, K.; Huynh, T.T.; Qin, N.; Bratslavsky, G.; Linehan, W.M.; Mannelli, M.; Friberg, P.; Grebe, S.K.; Timmers, H.J.L.M.; Bornstein, S.R.; Lenders, J.W.M.

    2011-01-01

    Phaeochromocytomas and paragangliomas (PPGLs) are highly heterogeneous tumours with variable catecholamine biochemical phenotypes and diverse hereditary backgrounds. This analysis of 18 catecholamine-related plasma and urinary biomarkers in 365 patients with PPGLs and 846 subjects without PPGLs

  20. PHEOCHROMOCYTOMA: A CATECHOLAMINE AND OXIDATIVE STRESS DISORDER

    Science.gov (United States)

    Pacak, Karel

    2012-01-01

    The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla — an intra-adrenal paraganglioma. Closely related tumors of extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. Almost all pheochromocytomas and paragangliomas produce catecholamines. The concentrations of catecholamines in pheochromocytoma tissues are enormous, potentially creating a volcano that can erupt at any time. Significant eruptions result in catecholamine storms called “attacks” or “spells”. Acute catecholamine crisis can strike unexpectedly, leaving traumatic memories of acute medical disaster that champions any intensive care unit. A very well-defined genotype-biochemical phenotype relationship exists, guiding proper and cost-effective genetic testing of patients with these tumors. Currently, the production of norepinephrine and epinephrine is optimally assessed by the measurement of their O-methylated metabolites, normetanephrine or metanephrine, respectively. Dopamine is a minor component, but some paragangliomas produce only this catecholamine or this together with norepinephrine. Methoxytyramine, the O-methylated metabolite of dopamine, is the best biochemical marker of these tumors. In those patients with equivocal biochemical results, a modified clonidine suppression test coupled with the measurement of plasma normetanephrine has recently been introduced. In addition to differences in catecholamine enzyme expression, the presence of either constitutive or regulated secretory pathways contributes further to the very unique mutation-dependent catecholamine production and release, resulting in various clinical presentations. Oxidative stress results from a significant imbalance between levels of prooxidants, generated during oxidative phosphorylation, and antioxidants. The gradual accumulation of prooxidants due to metabolic oxidative stress results in proto

  1. Blood and urine catecholamine concentrations after implantation of artificial heart.

    Science.gov (United States)

    Stanley, T H; Kennard, L; Isern-Amaral, J; Olsen, D; Lunn, J

    1976-05-01

    Plasma and urine epinephrine and norepinephrine concentrations were measured before and after implantation of an artificial heart in 20 calves and before and after thoracotomy in 3 control calves. All animals had similar preoperative plasma and urine catecholamine concentrations. During the first 4 postoperative days, plasma and urine epinephrine and norepinephrine concentrations were markedly elevated in all animals. However, calves with an artificial heart had significantly higher concentrations than control calves. Thereafter, catecholamine levels in control animals returned to preoperative levels, whereas epinephrine concentrations in artificial heart recipients remained elevated for 2 weeks and norepinephrine concentrations remained elevated for over a month. Two artifical heart recipeints survived longer than 2 months and had normal plasma and urine catecholamine concentrations from day 32 until a few days before being put to death. Although the mechanism in unclear, these findings suggest that early artificial heart function is associated with a significant metabolic stress which slowly disappears or becomes tolerable after one month.

  2. Alteration of brain levels of neurotransmitters and amino acids in male F344 rats induced by three-week repeated inhalation exposure to 1-bromopropane.

    Science.gov (United States)

    Suda, Megumi; Honma, Takeshi; Miyagawa, Muneyuki; Wang, Rui-Sheng

    2008-08-01

    The present study investigated the effects of 1-bromopropane (1BP) on brain neuroactive substances of rats to determine the extent of its toxicity to the central nervous system (CNS). We measured the changes in neurotransmitters (acetylcholine, catecholamine, serotonin and amino acids) and their metabolites or precursors in eight brain regions after inhalation exposure to 1BP at 50 to 1,000 ppm for 8 h per day for 7 d per week for 3 wk. Rats were sacrificed at 2 h (Case 1), or at 19 h (Case 2) after the end of exposure. In Case 1, the level of 5-hydroxyindoleacetic acid (5HIAA) was lowered in some brain regions by 1BP exposure. The decrease of 5HIAA in the frontal cortex was statistically significant at 50 ppm 1BP exposure. In Case 2, gamma-amino butyric acid (GABA) and taurine were decreased in many brain regions of exposed rats, and a significant decrease of taurine in the midbrain occurred at 50 ppm 1BP exposure. In both cases of 2-h and 19-h intervals from the end of exposure to sacrifice, aspartate and glutamine levels were elevated in many brain regions, but the acetylcholine level did not change in any brain region. Three-week repeated exposure to 1BP produced significantly changes in amino acid contents of rat brains, particularly at 1,000 ppm.

  3. Identifying Brain Image Level Endophenotypes in Epilepsy

    CERN Document Server

    Cheng, Wei; Tian, Ge; Feng, Jianfeng; Wang, Zhengge; Zhang, Zhiqiang; Lu, GuangMing

    2012-01-01

    A brain wide association study (BWAS) based on the logistic regression was first developed and applied to a large population of epilepsy patients (168) and healthy controls (136). It was found that the most significant links associated with epilepsy are those bilateral links with regions mainly belonging to the default mode network and subcortex, such as amygdala, fusiform gyrus, inferior temporal gyrus, hippocampus, temporal pole, parahippocampal gyrus, insula, middle occipital gyrus, cuneus. These links were found to have much higher odd ratios than other links, and all of them showed reduced functional couplings in patients compared with controls. Interestingly, with the increasing of the seizure onset frequency or duration of illness, the functional connection between these bilateral regions became further reduced. On the other hand, as a functional compensation and brain plasticity, connections of these bilateral regions to other brain regions were abnormally enhanced and became even much stronger with t...

  4. Middle cerebral artery blood velocity and plasma catecholamines during exercise

    DEFF Research Database (Denmark)

    Pott, F; Jensen, K; Hansen, H;

    1996-01-01

    During dynamic exercise, mean blood velocity (Vmean) in the middle cerebral artery (MCA) demonstrates a graded increase to work rate and reflects regional cerebral blood flow. At a high work rate, however, vasoactive levels of plasma catecholamines could mediate vasoconstriction of the MCA...

  5. Effect of copper deficiency on plasma and adrenal catecholamines

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, B.W.; Bhathena, S.J.; Fields, M.; Voyles, N.R.; Timmers, K.I.; Recant, L.

    1986-03-01

    Copper (Cu) ion is an essential component of enzymes involved in catecholamine (CAT) metabolism. Copper deficiency (CuD) has been shown to affect the CAT content of brain (decreased norepinephrine (NE) and dopamine (DA)) and heart (increased DA and decreased NE). It is thus possible that plasma and adrenal CAT could be altered by CuD. The authors, then, investigated the effect of CuD on plasma and adrenal CAT in rats fed copper-deficient (0.6 ..mu..g Cu/g) or copper-supplemented (6.0 ..mu..g Cu/g) diets with either 62% starch (S) or fructose (F) as the carbohydrate source for 7 weeks after weaning. CuD was ascertained by decreased plasma Cu and ceruloplasmin activity. CuD increased the levels of all three CAT (NE, P < 0.001, epinephrine (E), P < 0.0001 and DA, P < 0.01) in plasma, but had no effect on adrenal CAT content. Dietary F had no significant effect on plasma CAT compared to S but did increase E in adrenal tissue (P < 0.001). They have previously demonstrated that CuD is accompanied by increased plasma glucose, triglyceride and cholesterol and decreased insulin. Thus, increased plasma CAT along with decreased plasma insulin may explain, in part, the glucose intolerance and abnormal lipid metabolism observed in CuD.

  6. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Urinary catecholamines in iron deficiency anemia: effects of environmental temperature

    Energy Technology Data Exchange (ETDEWEB)

    Smith, S.M.; Beard, J.L.

    1986-03-05

    Iron deficiency (ID) is associated with increased levels of norepinephrine (NE) in plasma and urine. They investigated the effect of 5-7 days exposure to three different environmental temperatures (10/sup 0/C, 24/sup 0/C, 30/sup 0/C) on urinary catecholamine levels to test the hypothesis that increased thermogenic activity is causal to this increased excretion in iron deficiency. Catecholamines were analyzed from acidified urine by HPLC-EC. The mean Hb in ID animals was 3.1 +/- .5 versus controls of 12.8 +/- 9. These data demonstrate that contrary to previous reports NE excretion is not normalized at a thermoneutral temperature and suggests a basic abnormality in peripheral SNS activity and NE metabolism in iron deficiency that is independent of environmental drive from thermogenesis.

  8. Human brain mercury levels related to exposure to amalgam fillings.

    Science.gov (United States)

    Ertaş, E; Aksoy, A; Turla, A; Karaarslan, E S; Karaarslan, B; Aydın, A; Eken, A

    2014-08-01

    The safety of dental amalgam as the primary material in dental restoration treatments has been debated since its introduction. It is widely accepted that amalgam restorations continuously release elemental mercury (Hg) vapor, which is inhaled and absorbed by the body and distributed to tissues, including the brain. The aim of the present study was to investigate whether the presence of amalgam fillings is correlated with brain Hg level. The Hg levels in the parietal lobes of the brains of 32 cadavers were analyzed with an atomic absorption spectrometer with the mercury hydride system. A total of 32 brain samples were tested; of these, 10 were from cadavers with amalgam fillings, while 22 of them were amalgam free. Hg was detected in 60.0% (6 of 10) of the samples in the amalgam group and in 36.3% (8 of 22) in the amalgam-free group. The average Hg level of the amalgam group was 0.97 ± 0.83 µg/g (minimum: 0.3 µg/g and maximum: 2.34 µg/g), and in the amalgam-free group, it was 1.06 ± 0.57 µg/g (minimum: 0.17 µg/g and maximum: 1.76 µg/g). The results of the present study showed no correlation between the presence of amalgam fillings and brain Hg level.

  9. Sleep, brain energy levels, and food intake

    Science.gov (United States)

    Dworak, M.; Kim, T.; McCarley, R.W.; Basheer, R.

    2013-01-01

    Background The feeling of hunger and feeding, a wake–state-dependent behavior, is regulated by specific centers within the hypothalamus. While paraventricular nucleus (PVN), arcuate nucleus (ARC), and dorso- and ventromedial hypothalamus (DMH/VMH) regulate feeding, the lateral hypothalamus (LH) is associated both with feeding and wake/REM sleep regulation. In order to examine the effects of sleep and wakefulness on food intake and body weight, we also measured hypothalamic ATP concentrations, which are known to be involved in feeding behavior and sleep–wake regulation. Methods In rats, food intake and body weight was measured during a 24-h light–dark cycle and during 6 h of sleep deprivation (SD) performed by gentle handling. Tissue samples from the PVN, ARC/DMH/VMH, and LH were collected after 6 h of SD and from time-matched diurnal controls. ATP was measured by luciferin-luciferase bioluminescence assay. Results Across the 24-h light–dark period, rats consumed approximately 28.13±4.48 g of food and gained 5.22±1.65 g with a positive correlation between food intake and body weight. During SD, while food intake increased significantly +147.31±6.13%, they lost weight significantly (–93.29±13.64%) when compared to undisturbed controls. SD resulted in a significant decrease in ATP levels only in LH (–44.60±21.13%) with no change in PVN, ARC/DMH/VMH region when compared with undisturbed controls. Conclusion The results indicate a strong overall correlation between ATP concentrations in the LH and individual food intake and suggest a sleep–wake dependent neuronal control of food intake and body weight. PMID:23585726

  10. Reversible cardiogenic shock due to catecholamine-induced cardiomyopathy: a variant of takotsubo?

    Science.gov (United States)

    Law, Catherine; Khaliq, Asma; Guglin, Maya

    2013-11-01

    Catecholamine-induced cardiomyopathy, including takotsubo, neurogenic stunned myocardium, and pheochromocytoma-related cardiomyopathy, is a reversible and generally benign condition. We are reporting a case series of young women who had cardiogenic shock and pulmonary edema due to severe left ventricular systolic dysfunction, which completely recovered in the course of 2 to 3 weeks. Both patients had high catecholamine levels, due to pheochromocytoma in the first case and due to intravenous high-dose catecholamines in the second case. We suggest that screening for pheochromocytoma should be considered in patients who present with takotsubo cardiomyopathy without obvious cause. Most importantly, widely used intravenous catecholamines may cause severe transient left ventricular dysfunction, and consideration should be given to noncatecholamine vasopressors.

  11. High voltage electric potentials to enhance brain-derived neurotrophic factor levels in the brain.

    Science.gov (United States)

    Yanamoto, Hiroji; Nakajo, Yukako; Kataoka, Hiroharu; Iihara, Koji

    2013-01-01

    Development of a safe method to increase brain-derived neurotrophic factor (BDNF) levels in the brain is expected to enhance learning and memory, induce tolerance to cerebral infarction or tolerance to depressive state, improve glucose metabolism, and suppress appetite and body weight. We have shown that repetitive applications of high-voltage electric potential (HELP) to the body increase BDNF levels in the brain, improving learning and memory in mice. Here, we investigated the effects of HELP treatment for a chronic period on the BDNF levels in the mouse brain, and on body weight in mice and humans. Adult mice were exposed to 3.1 or 5.4 kV HELP (on the body), 5 h a day for 24 weeks, and BDNF levels in the brain and alterations in body weight were analyzed. Humans [age, 53.2 ± 15.5 years old; BMI, 27.8 ± 5.6 (mean ± SD, n = 6)] were exposed to 3.9 kV HELP (on the body) for 1 h a day, continuing for 33 months (2.8 years) under the monitor of body weight. In mice, the HELP application elevated BDNF levels in the brain at least temporarily, affecting body weight in a voltage- and time-dependent manner. In humans, the HELP treatment reduced body weight compared to the pretreated initial values without any aversive effects (p BDNF, and 5.4 kV HELP was considered as excessive. HELP with an appropriate voltage can be utilized to increase BDNF levels in the brain for a prolonged period. We anticipate further investigations to clarify the effect of the optimal-leveled HELP therapy on memory disturbances, neurological deficits after stroke, depression, diabetes, obesity and metabolic syndrome.

  12. Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    LJUBICA GAVRILOVIC

    2013-09-01

    Full Text Available ABSTRACT Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase and cyclic adenosine monophosphate response element-binding (CREB in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

  13. Human plasma DNP level after severe brain injury

    Institute of Scientific and Technical Information of China (English)

    GAO Yi-lu; XIN Hui-ning; FENG Yi; FAN Ji-wei

    2006-01-01

    Objective: To determine the relationship between DNP level after human severe brain injury and hyponatremia as well as isorrhea.Methods: The peripheral venous plasma as control was collected from 8 volunteers. The peripheral venous plasma from 14 severe brain injury patients were collected in the 1, 3, 7 days after injury. Radioimmunoassay was used to detect the DNP concentration. Meanwhile, daily plasma and urine electrolytes, osmotic pressure as well as 24 h liquid intake and output volume were detected.Results: The normal adult human plasma DNP level was 62. 46 pg/ml ± 27. 56 pg/ml. In the experimental group, the plasma DNP levels were higher from day 1 today 3 in 8 of the 14 patients than those in the control group (P1 =0.05, P3 =0.03). Negative fluid balance occurred in 8 patients and hyponatremia in 7 patients. The increase of plasma DNP level was significantly correlated with the development of a negative fluid balance (r=-0.69,P<0.01) and hyponatremia (x2 =4.38, P<0.05).Conclusions: The increase of plasma DNP level is accompanied by the enhancement of natriuretic and diuretic responses in severe brain-injured patients, which is associated with the development of a negative fluid balance and hyponatremia after brain injury.

  14. EFFECT OF MOXIBUSTION ON CATECHOLAMINE

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate whether moxibustion affects the secretion of catecholamine as adrenalin, noradrenaline and dopamine. Methods: Twenty Wistar rats were allocated to two groups. One was moxibustion-group (10 rats), and the other was non-moxibustion-group (10 rats). Four ignited moxa-cones were applied to bilateral "Shenshu" (肾俞 BL 23). When a moxa-cone burned out, another one was replaced. At the end of each experiment, blood sample (2 mL/rat) was collected from the heart for assaying plasma adrenalin, noradrenaline and dopamine contents with high pressure liquid chromatography. Results:The presented results showed that plasma adrenalin and noradrenaline contents of moxibustion-group are significantly higher than those of non-moxibustion-group (P<0.01). However, there is no significant difference of dopamine between moxibustion- and non-moxibustion- groups (P > 0.05). Conclusion: These results demonstrated that moxibustion stimulates the secretion of adrenaline and noradrenaline in normal rats.

  15. Decreased relative brain tissue levels of inositol in fetal hydrocephalus.

    NARCIS (Netherlands)

    Kok, R.D.; Steegers-Theunissen, R.P.M.; Eskes, T.K.A.B.; Heerschap, A.; Berg, P.P. van den

    2003-01-01

    OBJECTIVE: Inositol seems to play a role in the development of the central nervous system. In this study, the brain tissue level of inositol in fetal hydrocephalus was compared with that of healthy control subjects. STUDY DESIGN: Proton magnetic resonance spectroscopy was used to examine the inosito

  16. Blood and Brain Glutamate Levels in Children with Autistic Disorder

    Science.gov (United States)

    Hassan, Tamer H.; Abdelrahman, Hadeel M.; Fattah, Nelly R. Abdel; El-Masry, Nagda M.; Hashim, Haitham M.; El-Gerby, Khaled M.; Fattah, Nermin R. Abdel

    2013-01-01

    Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children…

  17. The influence of mode of delivery on the level of catecholamines in umbilical cord blood of neonates%分娩方式对新生儿脐血儿茶酚胺水平的影响

    Institute of Scientific and Technical Information of China (English)

    王静璇; 张为远

    2009-01-01

    Objective To determine whether mode of delivery is associated with the level of catecholamines in umbilical cord blood of neonates.Methods A study was carried out on 150 neonates. Among them 90 were healthy while 60 were diagnosed fetal distress. Then the subjects were first divided into 5 groups according to different modes of delivery: 30 were delivered by spontaneous labor for vaginal delivery without any pain relief;30 by vaginal delivery with epidural anaesthesia;30 by caesarean section without labor;30 by vaginal delivery with low forceps because of fetal distress and 30 by caesarean section of emergency because of fetal distress. After delivery, umbilical cord blood of both artery and vein was collected for determination of norepinephrine (NE), epinephrine(E), and dopamine (DA).Results (1) The concentration of NE and E of umbilical artery were different in each group (P<0.01), the group with the highest concentrations of NE and E was the ones delivered by vaginal delivery with low forceps[(73±6) ng/L,(37.8±1.8)ng/L] while caesarean section[(35±5) ng/L,(27.2±1.2) ng/L] was associated with significantly lower concentrations of NE and E of umbilical artery. The ones delivered by vaginal delivery with low forceps[(33.7±4.5) ng/L] and caesarean section of emergency [(32.9±4.5) ng/L] had higher concentrations of DA compared with any other group (P<0.01) . (2) The concentration of NE and E of umbilical vein were different in each group (P<0.01) just like that of umbilical artery. The ones delivered by vaginal delivery with low forceps and caesarean section of emergency had higher concentrations of DA compared with any other group (P<0.01) . (3) The neonates with fetal distress had higher levels of catecholamine both in umbilical artery and umbilical vein than the healthy ones(P<0.01) ;at the same time, the ones with fetal distress got lower Apgar scores 1, 5, 10 min after born contrasted to the healthy ones.Conclusions If no indication for caesarean

  18. Electrochemical sensors and biosensors for determination of catecholamine neurotransmitters: A review.

    Science.gov (United States)

    Ribeiro, José A; Fernandes, Paula M V; Pereira, Carlos M; Silva, F

    2016-11-01

    This work describes the state of the art of electrochemical devices for the detection of an important class of neurotransmitters: the catecholamines. This class of biogenic amines includes dopamine, noradrenaline (also called norepinephrine) and adrenaline (also called epinephrine). Researchers have focused on the role of catecholamine molecules within the human body because they are involved in many important biological functions and are commonly associated with several diseases, such as Alzheimer's and Parkinson. Furthermore, the release of catecholamines as a consequence of induced stimulus is an important indicator of reward-related behaviors, such as food, drink, sex and drug addiction. Thus, the development of simple, fast and sensitive electroanalytical methodologies for the determination of catecholamines is currently needed in clinical and biomedical fields, as they have the potential to serve as clinically relevant biomarkers for specific disease states or to monitor treatment efficacy. Currently, three main strategies have used by researchers to detect catecholamine molecules, namely: the use electrochemical materials in combination with, for example, HPLC or FIA, the incorporation of new materials/layers on the sensor surfaces (Tables 1-7) and in vivo detection, manly by using FSCV at CFMEs (Section 10). The developed methodologies were able not only to accurately detect catecholamines at relevant concentration levels, but to do so in the presence of co-existing interferences in samples detected (ascorbate, for example). This review examines the progress made in electrochemical sensors for the selective detection of catecholamines in the last 15 years, with special focus on highly innovative features introduced by nanotechnology. As the literature in rather extensive, we try to simplify this work by summarizing and grouping electrochemical sensors according to the manner their substrates were chemically modified. We also discuss the current and future

  19. Effects of mental workload and caffeine on catecholamines and blood pressure compared to performance variations.

    Science.gov (United States)

    Papadelis, Christos; Kourtidou-Papadeli, Chrysoula; Vlachogiannis, Emmanouil; Skepastianos, Petros; Bamidis, Panayiotis; Maglaveras, Nikos; Pappas, Kostantinos

    2003-02-01

    Caffeine is characterised as a central nervous system stimulant, also affecting metabolic and cardiovascular functions. A number of studies have demonstrated an effect of caffeine on the excretion of catecholamines and their metabolites. Urinary epinephrine and norepinephrine have been shown to increase after caffeine administration. Similar trends were observed in our study in adrenaline (ADR) and noradrenaline (NORADR) levels and additionally a dose dependent effect of caffeine. The effect of caffeine on cognitive performance, blood pressure, and catecholamines was tested under resting conditions and under mental workload. Each subject performed the test after oral administration of 1 cup and then 3 cups of coffee. Root mean square error (RMSE) for the tracking task was continuously monitored. Blood pressure was also recorded before and after each stage of the experiment. Catecholamines were collected and measured for three different conditions as: at rest, after mental stress alone, after one dose of caffeine under stress, and after triple dose of caffeine under stress. Comparison of the performance of each stage with the resting conditions revealed statistically significant differences between group of smokers/coffee drinkers compared with the other two groups of non-coffee drinkers/non-smokers and non-smokers/coffee drinkers. There was no statistically significant difference between the last two groups. There was an increase of urine adrenaline with 1 cup of coffee and statistically significant increase of urine noradrenaline. Both catecholamines were significantly increased with triple dose of caffeine. Mental workload increased catecholamines. There was a dose dependent effect of caffeine on catecholamines.

  20. Effect of domoic acid on brain amino acid levels.

    Science.gov (United States)

    Durán, R; Arufe, M C; Arias, B; Alfonso, M

    1995-03-01

    The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala, GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala, striatum, cortex and midbrain). The most affected amino acid is the GABA, the main inhibitory amino acid neurotransmitter, whereas glutamate, the main excitatory amino acid, is not affected. The rat brain regions that seem to be the main target of the Dom action belong to the limbic system (hippocampus, amygdala). The possible implication of the amino acids in the actions of Dom is also discussed.

  1. Catecholamine biosynthesis and secretion: physiological and pharmacological effects of secretin.

    Science.gov (United States)

    Mahata, Manjula; Zhang, Kuizing; Gayen, Jiaur R; Nandi, Suvobroto; Brar, Bhawanjit K; Ghosh, Sajalendu; Mahapatra, Nitish R; Taupenot, Laurent; O'Connor, Daniel T; Mahata, Sushil K

    2011-07-01

    Pituitary adenylyl cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) augment the biosynthesis of tyrosine hydroxylase (TH). We tested whether secretin belonging to the glucagon/PACAP/VIP superfamily would increase transcription of the tyrosine hydroxylase (Th) gene and modulate catecholamine secretion. Secretin activated transcription of the endogenous Th gene and its transfected promoter (EC(50) ∼4.6 nM) in pheochromocytoma (PC12) cells. This was abolished by pre-treatment with a secretin receptor (SCTR) antagonist and by inhibition of protein kinase A (PKA), mitogen-activated protein kinase, or CREB (cAMP response element-binding protein). In agreement, secretin increased PKA activity and induced phosphorylation of CREB and binding to Th CRE, suggesting secretin signaling to transcription via a PKA-CREB pathway. Secretin stimulated catecholamine secretion (EC(50) ∼3.5 μM) from PC12 cells, but this was inhibited by pre-treatment with VIP-preferring receptor (VPAC1)/PACAP-preferring receptor (PAC1) antagonists. Secretin-evoked secretion occurred without extracellular Ca(2+) and was abolished by intracellular Ca(2+) chelation. Secretin augmented phospholipase C (PLC) activity and increased inositol-1,4,5-triphosphate (IP(3)) levels in PC12 cells; PLC-β inhibition blocked secretin-induced catecholamine secretion, indicating the participation of intracellular Ca(2+) from a phospholipase pathway in secretion. Like PACAP, secretin evoked long-lasting catecholamine secretion, even after only a transient exposure. Thus, transcription is triggered by nanomolar concentrations of the peptide through SCTR, with signaling along the cAMP-PKA and extracellular-signal-regulated kinase 1/2 pathways and through CREB. By contrast, secretion is triggered only by micromolar concentrations of peptide through PAC1/VPAC receptors and by utilizing a PLC/intracellular Ca(2+) pathway.

  2. Catecholamines in amniotic fluid as indicators of intrapartum fetal stress.

    Directory of Open Access Journals (Sweden)

    Yashiro,Yuriko

    1985-08-01

    Full Text Available Catecholamines were measured in the amniotic fluid and in the first voided newborn urine obtained from appropriate-for-date infants of term deliveries. Catecholamine values in the amniotic fluid and urine were nearly equal when expressed in terms of creatinine. Significant positive correlations were observed between the amniotic fluid and urine of norepinephrine and epinephrine. In normal cases (n = 32 that underwent uneventful vaginal delivery, the 95% confidence limits for norepinephrine and epinephrine in the amniotic fluid were 1.53 to 2.33 ng/ml and 0.16 to 0.30 ng/ml, respectively. In cases of moderate stress (n = 12, only norepinephrine showed significantly higher values than the normal cases, while in cases of severe stress (n = 12, norepinephrine became more significantly high, and epinephrine was found to be elevated significantly. A significant difference was noted in the incidence of fetal stress between the infants with more than and those with less than 2.30 ng/ml of norepinephrine, the upper limits of the normal 95% confidence limits. However, for epinephrine such a significant difference was not noted. It was concluded that amniotic fluid catecholamines are of fetal origin and reflect fetal sympathoadrenal activity directly, even during labor, and that their level may be a good indicator of fetal condition and stress.

  3. [The diagnosis of phaeochromocytoma: sensitivity of vanillylmandelic acid and urinary catecholamine determination and the Katecult test (author's transl)].

    Science.gov (United States)

    Cordes, U; Kümmerle, F; Philipp, T; Beyer, J

    1979-09-21

    Tumour weight was compared with maximal vanillylmandelic acid and catecholamine excretion in 24-hour urine in 21 patients with phaeochromocytoma. The tumour weight correlated both with vanillylmandelic acid (r = 0.805, P less than 0.001) as well as urinary catecholamine levels (r = 0.725, P less than 0.001). Normal vanillylmandelic acid excretion was found in seven patients; urinary catecholamine levels were abnormal in all patients. The Katecult test was additionally performed in ten patients, with nine positive results.

  4. Effect of microgravity on plasma catecholamine responses to stressors during space flight.

    Science.gov (United States)

    Kvetnansky, R; Macho, L; Koska, J; Pacak, K; Hoff, T; Ksinantova, L; Noskov, V B; Kobzev, E; Grigoriev, A I; Vigas, M

    2001-07-01

    The effect of microgravity on the sympathicoadrenal system (SAS) activity in humans and animals has not yet been clarified. Our previous studies suggested that the SAS activity, evaluated by circulating and/or urinary catecholamine (CA) levels in astronauts during space flights, was found to be rather unchanged. However, CA levels were measured in astronauts only at rest conditions. The aim of the present study was to investigate effect of microgravity during space flight and post-flight readaptation on responsiveness of the SAS to somatic and psychic stressors evaluated by levels of catecholamines and their metabolite in the blood of the Slovak cosmonaut during his stay on board the space station Mir.

  5. Microdialysis monitoring of catecholamines and excitatory amino acids in the rat and mouse brain: recent developments based on capillary electrophoresis with laser-induced fluorescence detection--a mini-review.

    Science.gov (United States)

    Parrot, Sandrine; Bert, Lionel; Mouly-Badina, Laurence; Sauvinet, Valérie; Colussi-Mas, Joyce; Lambás-Señas, Laura; Robert, Frédéric; Bouilloux, Jean-Pierre; Suaud-Chagny, Marie-Françoise; Denoroy, Luc; Renaud, Bernard

    2003-10-01

    1. Although microdialysis is a widely used approach for in vivo monitoring extracellular neurotransmitter concentrations, it has been previously limited in many cases by its poor temporal resolution. It is clear that when 10-30-min sampling is performed, short-lasting changes in extracellular neurotransmitter concentrations can be overlooked. Such a low sampling rate is necessary when combining microdialysis with the conventional analytical methods like high performance liquid chromatography. 2. Since capillary electrophoresis coupled to laser-induced fluorescence detection (CE-LIFD) allows the detection of attomoles of neurotransmitters, the temporal resolution of microdialysis may be significantly improved: high sampling rates, in the range of 5 s to 1 min, have been already reported by our group and others using CE-LIFD for simultaneously analyzing catecholamines and amino acids in microdialysates. 3. The power of combining microdialyis and CE-LIFD is shown, using examples of physiological and pharmacological studies dealing with the dynamics of in vivo efflux processes and/or interactions between neurotransmitters.

  6. Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice.

    Science.gov (United States)

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Giatti, Silvia; Caruso, Donatella; Viveros, Maria-Paz; Melcangi, Roberto C; Garcia-Segura, Luis M

    2015-06-01

    Traumatic brain injury (TBI) is an important cause of disability in humans. Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are neuroprotective in TBI models. However in order to design potential neuroprotective strategies based on neuroactive steroids it is important to determine whether its brain levels are altered by TBI. In this study we have used a weight-drop model of TBI in young adult female mice to determine the levels of neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after injury. We have also analyzed whether the levels of neuroactive steroids after TBI correlated with the neurological score of the animals. TBI caused neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after injury. Brain levels of progesterone, tetrahydroprogesterone (THP), isopregnanolone and 17β-estradiol were decreased 24h, 72 h and 2 weeks after TBI. DHEA and brain testosterone levels presented a transient decrease at 24h after lesion. Brain levels of progesterone and DHEA showed a positive correlation with neurological recovery. Plasma analyses showed that progesterone was decreased 72 h after lesion but, in contrast with brain progesterone, its levels did not correlate with neurological deficit. These findings indicate that TBI alters the levels of neuroactive steroids in the brain with independence of its plasma levels and suggest that the pharmacological increase in the brain of the levels of progesterone and DHEA may result in the improvement of neurological recovery after TBI.

  7. Renalase, a catecholamine-metabolising enzyme?

    NARCIS (Netherlands)

    F. Boomsma (Frans); K.F. Tipton

    2007-01-01

    textabstractRecently, a new FAD-dependent amine oxidase, renalase, was described. It was secreted by the kidney into the blood and shown to have significant cardiovascular actions, which were attributed to its catecholamine-metabolising activity. The authors concluded that renalase might be an

  8. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    Science.gov (United States)

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

  9. Catecholamine-containing nerve fibres in the human abdominal vagus.

    Science.gov (United States)

    Lundberg, J; Ahlman, H; Dahlström, A; Kewenter, J

    1976-03-01

    The vagal nerve of man has been investigated for the presence of adrenergic nerve fibres using the histochemical fluorescence method of Hillarp and Falck. Following 30-60 min of nerve ligation during surgical operations, the right anterior main trunk (subdiafragmatic level) from one patient, and the anterior nerve of Latarget of 5 patients were found to contain unmyelinated nerve fibres with accumulations of green fluorescent material representing a catecholamine. The observations indicate the presence of adrenergic nerve fibres running caudally in the human vagal nerve, in accordance with similar findings in other mammals, e.g. cats and dogs.

  10. Increased gene expression of catecholamine-synthesizing enzymes in adrenal glands contributes to high circulating catecholamines in pigs with tachycardia-induced cardiomyopathy.

    Science.gov (United States)

    Tomaszek, A; Kiczak, L; Bania, J; Paslawska, U; Zacharski, M; Janiszewski, A; Noszczyk-Nowak, A; Dziegiel, P; Kuropka, P; Ponikowski, P; Jankowska, E A

    2015-04-01

    High levels of circulating catecholamines have been established as fundamental pathophysiological elements of heart failure (HF). However, it is unclear whether the increased gene expression of catecholamine-synthesis enzymes in the adrenal glands contributes to these hormone abnormalities in large animal HF models. We analyzed the mRNA levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AAAD), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands of 18 pigs with chronic systolic non-ischaemic HF (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 sham-operated controls. Pigs with severe HF demonstrated an increased expression of TH and DBH (but neither AAAD nor PNMT) as compared to animals with milder HF and controls (Padrenal mRNA expression of TH and DBH was accompanied by a reduced left ventricle ejection fraction (LVEF) (Padrenal mRNA expression of TH and DBH, and the high levels of circulating adrenaline and noradrenaline (all Padrenals to the circulating pool of catecholamines in subjects with systolic HF.

  11. Selection for low mortality in laying hens affects catecholamine levels in the arcopallium, a brain area involved in fear and motor regulation

    NARCIS (Netherlands)

    Kops, M.S.; Haas, de E.N.; Rodenburg, T.B.; Ellen, E.D.; Korte-Bouws, G.A.H.; Olivier, B.; Güntürkün, O.; Korte, S.M.; Bolhuis, J.E.

    2013-01-01

    Feather pecking (FP) in laying hens may cause mortality due to cannibalism. Novel breeding methods using survival days of group-housed siblings allow for the genetic selection of laying hens with low mortality (LML: low mortality line) due to cannibalism. Previous studies have demonstrated less fear

  12. 射击运动员赛前焦虑和尿儿茶酚胺水平变化分析%Precompetitive Anxiety and the Level of Urinary Catecholamine in Shooters

    Institute of Scientific and Technical Information of China (English)

    汪喆

    2011-01-01

    Objective To study the relation of urinary catecholamine level to the precompetitive anxiety state in shooters. Methods Morning urinary adrenaline, noradrenaline and dopamine levels were determined with high-performance liquid chromatography in 20 shooters 4 weeks (T1) , 2 weeks (T2) and 1 week (T3) before a domestic competition. According to the CSAI-2, scores of cognitive state anxiety (S1) . somatic state anxiety (S2) and the state of self-confidence (S3) were obtained. Results The urinary excretions of adrenaline and dopamine in T2 and T3 increased respectively as compared with that in T1 and T2 (P < 0.05 ) ; and the scores of S1 and S2 in T1 and T2 were respectively higher than that in T2 and T3 (P < 0.05) , while S3 remained unchanged. The correlation coefficients between S1 and adrenaline, S2 and adrenaline, and S2 and dopamine in T1. T2 and T3 were 0.80, 0.65 and 0.73 (P < 0.05) , 0.69, 0.77 and 0.62 (P < 0.05) , and 0.61, 0.42 and 0.46 (P < 0.05 ) , respectively. Conclusion Urinary epinephrine and dopamine levels highly correlate to the precompetitive anxiety state in shooters, and thus can be used for determining the state of anxiety before competition.%目的:研究射击运动员赛前焦虑和尿儿茶酚胺水平的变化,探寻判断运动员赛前焦虑的方法.方法:利用高效液相色谱分析技术,分别测定20名上海市射击运动员在一场国内比赛前4周(T1)、2周(T2)和1周(T3)时晨尿肾上腺素、去甲肾上腺素和多巴胺的水平,采用运动竞赛状态焦虑量表,测量并结合认知状态焦虑(S1)、躯体状态焦虑(S2)和状态自信心(S3)得分,进行统计分析,寻找反映赛前焦虑的特征性指标.结果:运动员尿肾上腺素和多巴胺排出量T2时段较T1时段、T3时段较T2时段均显著升高(P<0.05),运动竞赛状态焦虑量表S1和S2得分T2时段较T1时段、T3时段较T2时段均显著升高(P<0.05),而T3时段S3得分较T2时段无明显变化.T1、T2、T3时段认知状态

  13. Effects of acute diuresis stress on egr-1 (zif268) mRNA levels in brain regions associated with motivated behavior.

    Science.gov (United States)

    Aher, Chetan V; Duwaerts, Caroline C; Akama, Keith T; Lucas, Louis R

    2010-01-15

    Stressors evoke a well-studied physiological stress-response, namely, an immediate systemic release of catecholamines from the adrenals followed shortly afterwards by the release of adrenal steroids. The intensity of that response can often be inferred by the amount of adrenal steroids released into the circulatory system. It is still unclear however how the intensity and duration of the stressor affect a number of brain regions, including those in the motivational system. The present study sought to determine whether a brief stressor, such as an isotonic saline injection, activated the brain's motivational system in mesolimbic regions compared with a more intense stressor exemplified by pharmacological challenges caused by the administration of a diuretic. Adult male Sprague-Dawley rats were either injected (s.c.) with isotonic saline or 5mg of the diuretic, furosemide. Controls did not receive any injections. Animals were sacrificed at 30, 60, 120, and 240 min after injection and trunk blood and brains were collected. Serum corticosterone and aldosterone levels were assessed through radioimmunoassay and mesolimbic brain activity was determined through in situ hybridization of mRNA expression of the immediate-early gene egr-1 in the caudate-putamen and nucleus accumbens. While both adrenal steroids demonstrated an initial peak in both stress groups, levels were higher and longer lasting in rats treated with furosemide. Interestingly, egr-1 mRNA levels were significantly higher only in the furosemide-treated group compared with controls. These findings suggest that a selective activation of motivational circuits occurs under thirst and salt-appetite-induced conditions such as those caused by diuresis.

  14. Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation

    DEFF Research Database (Denmark)

    Johansson, P I; Ostrowski, S R

    2010-01-01

    .e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally......Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i......, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant...

  15. Low-level light therapy of the eye and brain

    Directory of Open Access Journals (Sweden)

    Rojas JC

    2011-10-01

    Full Text Available Julio C Rojas1,2, F Gonzalez-Lima1 1Departments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX; 2Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA Abstract: Low-level light therapy (LLLT using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases

  16. [Pharmacological influences on the brain level and transport of GABA. II) Effect of various psychoactive drugs on brain level and uptake of GABA].

    Science.gov (United States)

    Gabana, M A; Varotto, M; Saladini, M; Zanchin, G; Battistin, L

    1981-04-30

    The effects of some psychoactive drugs on the level and uptake of GABA in the mouse brain was studied using well standardized procedures, mainely the silica-gel cromatography for determining the GABA content and the brain slices for measuring GABA uptake. It was found that levomepromazine, sulpiride, haloperidol and amytryptiline were without effects on the cerebral level of GABA; it was also found that these drugs do not influence the rates of uptake of GABA by mouse brain slices. Such results do indicate that the psychoactive drugs studied are without effects on the level and uptake of GABA in the brain.

  17. Time control, catecholamines and back pain among young nurses.

    Science.gov (United States)

    Elfering, Achim; Grebner, Simone; Semmer, Norbert K; Gerber, Hans

    2002-12-01

    This study had two objectives. First, it addressed concern with the contribution of work stressors and resources to the development of back pain, over and above the influence of biomechanical work factors. Second, using recent models about the role of the sympathetic-adrenal medullar system in musculoskeletal problems as its basis, it tested whether low-back pain is associated with higher levels of catecholamines. Altogether 114 nurses filled out a questionnaire in their first year of practice and again one year later. In addition, in a subsample of 24 nurses studied intensively at follow-up, urinary catecholamines were assessed at noon, before the end of work, in the evening, and at corresponding times on a day off. Daily stressful experiences and daily mood were also recorded. With control for baseline pain, biomechanical workload, and other potentially confounding variables, time control at the beginning of the study predicted low-back pain a year later. In the subsample, the epinephrine and norepinephrine levels were higher in those reporting more frequent episodes of back pain, the largest differences occurring at the end of work. In addition, control over stressful events at work was lower in this group. Time control is a risk factor for low-back pain among nurses beyond the influence of physical work load. Low control at work may increase the activity of the sympathetic-adrenal medullar system, which seems to play an important role in the development of musculoskeletal pain.

  18. Plasma catecholamine concentrations associated with cerebral vasospasm.

    Science.gov (United States)

    Loach, A B; Benedict, C R

    1980-03-01

    Plasma concentrations of adrenaline and noradrenaline were measured sequentially over the immediate post-operative period following clipping of an intracranial aneurysm in 11 patients. Those patients who developed local cerebral vasospasm showed a sustained rise in plasma catecholamines, particularly noradrenaline, whilst those patients who developed generalised cerebral vasospasm showed early peaks of very high concentrations of adrenaline and noradrenaline which preceded radiological evidence of generalized vasospam.

  19. Mapping how local perturbations influence systems-level brain dynamics

    OpenAIRE

    Gollo, Leonardo L.; James A. Roberts; Cocchi, Luca

    2016-01-01

    The human brain exhibits a relatively stable spatiotemporal organization that supports brain function and can be manipulated via local brain stimulation. Such perturbations to local cortical dynamics are globally integrated by distinct neural systems. However, it remains unclear how and why local changes in neural activity affect large-scale system dynamics. Here, we briefly review empirical and computational studies addressing how localized perturbations affect brain activity. We then system...

  20. Possible space flight-induced catecholamine cardiomyopathy: Neil Armstrong's last 20 lunar minutes

    Directory of Open Access Journals (Sweden)

    Rowe WJ

    2014-01-01

    Full Text Available William J RoweFormer Assistant Clinical Professor of Medicine, Medical University of Ohio at Toledo, Ohio, USAAbstract: The hypothesis underpinning this paper is that space flight may predispose to catecholamine cardiomyopathy. Catecholamine levels in space are twice those of the supine levels on Earth. Serum magnesium levels are significantly reduced, with potential vicious cycles triggered by elevation of catecholamines. These are conducive to coronary vasospasm with clot formation from oxidative stress and calcium overload, and ultimately, temporary impairment of left ventricular function could occur. Experimental animals in space have shown a significant increase in norepinephrine levels with various microcirculatory disorders and serious myocardial pathology. During extravehicular activity (space walks, astronauts show heart rates of 150–174 beats per minute. Before exposure to the iron-laden dust brought into the habitat on his space suit, Neil Armstrong's heart rates on the lunar surface were 130–160 beats per minute, and accompanied by dyspnea on two occasions during his last 20 minutes on the moon. A stress test done on the day after splashdown was consistent with "ischemic left ventricular dysfunction". To support this hypothesis, echocardiography on the international space station might show left ventricular hypokinesia. Alpha adrenergic blockade, correction of invariable significant magnesium deficits, along with correction of invariable atrial natriuretic peptide deficits, may counteract the vasoconstrictive action of norepinephrine.Keywords: space flight, catecholamines, cardiomyopathy, magnesium, oxidative stress, heat intolerance, calcium

  1. Modified monolithic silica capillary for preconcentration of catecholamines

    Institute of Scientific and Technical Information of China (English)

    Wei Chang; Tusyo-shi Komazu

    2009-01-01

    Preconcentration of catecholamines by the modified monolithic silica in the capillary was investigated in this study. In order to achieve a microchip-based method for determining catecholamines in the saliva, the monolithic silica was fabricated in the capillary and the monolithic silica was chemically modified by on-column reaction with phenylboronate. Different modified methods were compared. The concentration conditions were optimized. This study indicates the applicability of the modified monolithic silica capillary when it was used to concentrate catecholamines.

  2. Identification of catecholamine neurotransmitters using fluorescence sensor array

    Energy Technology Data Exchange (ETDEWEB)

    Ghasemi, Forough [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of); Hormozi-Nezhad, M. Reza, E-mail: hormozi@sharif.edu [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of); Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Mahmoudi, Morteza, E-mail: mahmoudi@stanford.edu [Department of Nanotechnology and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 13169-43551 (Iran, Islamic Republic of); Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305-5101 (United States)

    2016-04-21

    A nano-based sensor array has been developed for identification and discrimination of catecholamine neurotransmitters based on optical properties of their oxidation products under alkaline conditions. To produce distinct fluorescence response patterns for individual catecholamine, quenching of thioglycolic acid functionalized cadmium telluride (CdTe) quantum dots, by oxidation products, were employed along with the variation of fluorescence spectra of oxidation products. The spectral changes were analyzed with hierarchical cluster analysis (HCA) and principal component analysis (PCA) to identify catecholamine patterns. The proposed sensor could efficiently discriminate the individual catecholamine (i.e., dopamine, norepinephrine, and L-DOPA) and their mixtures in the concentration range of 0.25–30 μmol L{sup −1}. Finally, we found that the sensor had capability to identify the various catecholamines in urine sample. - Highlights: • We have proposed a fluorescence sensor array to detect catecholamine neurotransmitters. • Visual differentiation of catecholamines is provided by fluorescence array fingerprints. • Discrimination of catecholamines from each other, and from their mixture is obtained on a PCA plot. • Proposed sensor array can be used for detection of catecholamines in urine samples.

  3. Factors influencing brain natriuretic peptide levels in healthy pregnant women.

    Science.gov (United States)

    Mayama, Michinori; Yoshihara, Masato; Uno, Kaname; Tano, Sho; Takeda, Takehiko; Ukai, Mayu; Kishigami, Yasuyuki; Oguchi, Hidenori

    2017-02-01

    The normal range of plasma brain natriuretic peptide (BNP) in pregnant women is still unclear. Moreover, pregnant women experience dynamic body weight changes and suffer from anemia, but effects on maternal BNP have not been investigated. This study aimed to reveal the normal plasma BNP range and examine the effects of physiological changes on BNP among pregnant women. Plasma BNP, hemoglobin, plasma creatinine and BMI were measured in 58 non-pregnant control women and in 773 normal pregnant women at late pregnancy, early postpartum and 1-month postpartum. Mean plasma BNP (in pg/mL) was 11.8 (95% confidence interval: 0-27.5) in non-pregnant women, 17.9 (0-44.7, pchange during pregnancy (p=0.001) and post-delivery creatinine (p=0.010) but negatively associated with body weight loss at delivery (pchanges, creatinine and hemoglobin levels; therefore, these factors should be considered when analysing cardiac function and the physiological implications of BNP levels in pregnant women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment

    Directory of Open Access Journals (Sweden)

    NATASA SPASOJEVIC

    2015-03-01

    Full Text Available We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

  5. Effects of water immersion on plasma catecholamines in normal humans

    Science.gov (United States)

    Epstein, M.; Johnson, G.; Denunzio, A. G.

    1983-01-01

    An investigation was conducted in order to determine whether water immersion to the neck (NI) alters plasma catecholamines in normal humans. Eight normal subjects were studied during a seated control study (C) and during 4 hr of NI, and the levels of norepinephrine (NE) and epinephrine (E) as determined by radioenzymatic assay were measured hourly. Results show that despite the induction of a marked natriuresis and diuresis indicating significant central hypervolemia, NI failed to alter plasma NE or E levels compared with those of either C or the corresponding prestudy 1.5 hr. In addition, the diuresis and natriuresis was found to vary independently of NE. These results indicate that the response of the sympathetic nervous system to acute volume alteration may differ from the reported response to chronic volume expansion.

  6. The effect of sleep apnea on plasma and urinary catecholamines.

    Science.gov (United States)

    Dimsdale, J E; Coy, T; Ziegler, M G; Ancoli-Israel, S; Clausen, J

    1995-06-01

    Numerous studies have suggested an alteration of sympathetic nervous system functioning in sleep apnea. However, most of these studies did not control for confounding factors such as diet, obesity, hypertension and anti-hypertensive medications. We examined plasma and urinary catecholamines in 43 patients, including hypertensive and normotensive individuals with and without sleep apnea. Hypertensive patients were studied at least 3 weeks following tapering of anti-hypertensive medication. All patients consumed similar diets and were of similar age and level of obesity. Twenty-four-hour urinary norepinephrine levels were significantly higher in apneics (58.2 ng vs. 40.2 ng in nonapneics, p sleep and in the morning (p < 0.05).

  7. Chronic physical stress changes gene expression of catecholamine biosynthetic enzymes in the adrenal medulla of adult rats

    Directory of Open Access Journals (Sweden)

    Gavrilović Ljubica

    2012-01-01

    Full Text Available In this study we examined how chronic forced running (CFR affects the expression of catecholamine biosynthetic enzymes and cAMP response element-binding (CREB in the adrenal medulla and the weight of adrenal glands of rats. Also, we examined how CFR and additional acute immobilization stress affect the expression of catecholamine biosynthetic enzymes in the adrenal medulla and the concentration of catecholamines and corticosterone (CORT in the blood plasma. In this experiment we used as a model forced exercise in rats (treadmill running. We used the most advanced method for determining the level of gene expression, Real-time PCR with TaqMan probes, as well as Western blot analysis (ECL. We found that CFR decreases tyrosine hydroxylase (TH, and dopamine-β-hydroxylase (DBH mRNA and protein levels in the adrenal medulla. The decreased TH and DBH mRNA levels coincide with the reduced expression of CREB in the adrenal medulla and with the reduced plasma CORT level. Additionally, CFR reduces the level of phenylethanolamine N-methyltransferase (PNMT mRNA, but elevates its protein level in the adrenal medulla and increases the concentration of adrenaline (A in the plasma. Reduced level of PNMT mRNA in the adrenal medulla coincides with reduced plasma CORT level. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. The increased synthesis of PNMT enzyme in the adrenal medulla may result in an increased biosynthesis of A under chronic stress conditions. Additionally, increased level of catecholamines in the plasma after chronic physical stress is the allostatic load that may induce numerous diseases and pathological conditions.

  8. 脑出血大鼠肠黏膜组织形态学变化与血浆儿茶酚胺水平的关系%Correlation between intestinal mucosa tissue morphologic parameters and plasma catecholamines level in rats with cerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    邱月; 宁显忠

    2012-01-01

    目的 探讨脑出血大鼠肠黏膜组织形态学变化与血浆儿茶酚胺(肾上腺素、去甲肾上腺素)水平之间的关系.方法 制作脑出血大鼠模型,检测正常组、假手术组及脑出血后24h、48h、72h(每组8只)肠黏膜组织形态学参数及血浆肾上腺素、去甲肾上腺素水平.进行空肠黏膜组织形态学参数值与血浆肾上腺素、去甲肾上腺素水平之间的相关分析.结果 小肠绒毛高度与血浆肾上腺素(r=-0.566,P<0.01)、血浆去甲肾上腺索(r=-0.545,P<0.01);绒毛面积与血浆肾上腺素(r=-0.755,P<0.01)、血浆去甲肾上腺素(r=-0.702,P <0.01);黏膜厚度与血浆肾上腺素(r=-0.478,P<0.01)、血浆去甲肾上腺素(r=-0.405,P<0.01);肠壁厚度与与血浆肾上腺素(r=-0.536,P<0.01)、血浆去甲肾上腺素肠(r=-0.489,P<0.01)均成显著的负相关.结论 脑出血时肠黏膜组织形态学变化与血浆儿茶酚胺水平呈负相关.%Objective To explore the correlation between intestinal mucosa tissue morphologic changes and plasma catecholamines(adrenaline and nurepinephrine) level in rats with cerebral hemorrhage. Methods A rat model of hemorrhage was used to detect the intestinal mucosa tissue morphologic parameters changes and the plasma catecholamines (adrenaline and norepinephrine) level at 24h,48h and 72h after the hemorrhage. The results were compared to normal control group and the sham-operated group. The correlation between the jejunal mucosa tissue morphologic parameters changes and plasma adrenaline and plasma norepinephrine were also explored. Results Small intestinal villous height was negatively correlated with the level of plasma adrenaline (r = - 0. 566, P < 0. 01) and plasma norepinephrine (r = - 0. 545, P < 0.01) . Small intestinal villous area was negatively correlated with the level of plasma adrenaline ( r = - 0. 755, P < 0. 01 ) and plasma norepinephrine( r = - 0. 702, P < 0. 01). Mucosal thickness was negatively

  9. Stability of catecholamines in whole blood, plasma, and platelets.

    Science.gov (United States)

    Weir, T B; Smith, C C; Round, J M; Betteridge, D J

    1986-05-01

    Checking catecholamine stability in whole blood, plasma, and platelets, we found that specimens stored at room temperature or frozen for periods ranging from 1.5 h to three weeks show no significant difference in measured catecholamine concentration. The implications of these findings are discussed.

  10. Profiles of secreted neuropeptides and catecholamines illustrate similarities and differences in response to stimulation by distinct secretagogues.

    Science.gov (United States)

    Podvin, Sonia; Bundey, Richard; Toneff, Thomas; Ziegler, Michael; Hook, Vivian

    2015-09-01

    The goal of this study was to define profiles of secreted neuropeptide and catecholamine neurotransmitters that undergo co-release from sympathoadrenal chromaffin cells upon stimulation by distinct secretagogues. Chromaffin cells of the adrenal medulla participate in the dynamic responses to stress, especially that of 'fight and flight', and, thus, analyses of the co-release of multiple neurotransmitters is necessary to gain knowledge of how the stress response regulates cell-cell communication among physiological systems. Results of this study demonstrated that six different secretagogues stimulated the co-release of the neuropeptides Met-enkephalin, galanin, NPY, and VIP with the catecholamines dopamine, norepinephrine, and epinephrine. Importantly, the quantitative profiles of the secreted neurotransmitters showed similarities and differences upon stimulation by the different secretagogues evaluated, composed of KCl depolarization, nicotine, carbachol, PACAP, bradykinin, and histamine. The rank-orders of the secreted profiles of the neurotransmitters were generally similar among these secretagogues, but differences in the secreted amounts of each neurotransmitter occurred with different secretagogues. Epinephrine among the catecholamines showed the highest level of secretion. (Met)enkephalin showed the largest levels of secretion compared to the other neuropeptides examined. Levels of secreted catecholamines were greater than that of the neuropeptides. These data support the hypothesis that profiles of secreted neuropeptide and catecholamine neurotransmitters show similarities and differences upon stimulation by distinct secretagogues. These results illustrate the co-release of concerted neurotransmitter profiles that participate in the stress response of the sympathoadrenal nervous system.

  11. Evidence for extratumoural storage of catecholamines in pheochromocytoma patients.

    Science.gov (United States)

    Hengstmann, J H; Dengler, H J

    1978-03-01

    Following the removal of a pheochromocytoma in three female patients the daily excretion of catecholamines and their metabolites was still considerably elevated for about one week. The excretion rates declined during this period with half-lives of 1.8 to 10.9 days for catecholamines and 2.1 to 4.7 days for metanephrines, vanilmandelic acid, and vanilglycol. The cumulative urinary excretion of catecholamines and their metabolites following surgical removal of the tumour was nearly as high as the catecholamine content of the pheochromocytomas. This large amount of catecholamines must have been located outside the tumour, most probably within the sympathetic nerve, where it is subject to release following physiological stimuli. Furthermore, this fact may provide an explanation for hypertensive crises in pheochromocytoma patients.

  12. Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus

    OpenAIRE

    2015-01-01

    Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the...

  13. Plasma and erythrocyte relationship of catecholamines in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Marcin Dziedzic

    2014-09-01

    Full Text Available The function of the autonomic nervous system is based on reciprocal interaction between the sympathetic and parasympathetic parts, most frequently in the form of antagonistic action on target organs. The main mediators of the sympathetic nervous system in the effectors part are catecholamines (CA, which are involved in various physiological processes. Moreover, CA also has a profound effect on the kidneys, being factors that impact on renal haemodynamics, and have been reported to be altered in pathological disorders, e.g. extracellular volume expression, hypertension and cardiovascular complications. The increased sympathetic nerve activity, at least in part, can explain the raised in plasma CA observed in chronic kidney diseases. Furthermore, plasma CA levels in ureamic patients cannot be considered a reliable index of sympathetic activity, due to existence of many factors which may affect their values. In addition, CA released into the circulation, as one of many substances, may penetrate across the cellular membranes of erytrocytes (RBC. Taking these observations together, the aim of the presented study was to investigate for the first time the plasma and erythrocyte relationship of catecholamines in haemodialysis. The studies were performed among 37 haemodialysed patients who were inhabitants of the Lublin commune. Plasma and intracellular concentration of CA were measured prior to and following haemodialysis by high performance liquid chromatography with electrochemical detection. The results suggest that RBC are able to accumulate CA at the stage of terminal renal failure; in addition, the levels of adrenaline and dopamine in RBC depend on the accumulation of urea in plasma. It was also found that the dynamic changes in concentration of RBC adrenaline are an independent predictor of mortality in haemodialysis patients.

  14. Effects of Ivabradine Tablets on Heart Function and Serum Catecholamine Level in Patients with Heart Failure%伊伐布雷定片对心力衰竭患者心功能及血清儿茶酚胺水平的影响

    Institute of Scientific and Technical Information of China (English)

    夏志高; 言洁; 朱幸仪

    2016-01-01

    目的:观察伊伐布雷定片对心力衰竭(简称心衰)患者心功能及血清儿茶酚胺水平的影响。方法选取医院门诊部2015年1月至2016年1月收治的心衰患者78例,采用随机数字表法分为研究组和对照组,各39例。对照组患者给予常规药物治疗,研究组患者在对照组基础上加用伊伐布雷定片,观察并比较两组患者治疗后的心功能指标[射血分数(EF)、左室内径(LV)]、血清儿茶酚胺[去甲肾上腺素(NA)、肾上腺素(Adr)]水平变化及药品不良反应发生情况。结果治疗后,对照组患者EF较治疗前显著减小,LV显著增大,研究组患者EF较对照组显著增大,LV显著减小,差异均有统计学意义( P0.05)。结论伊伐布雷定片可有效改善心衰患者心功能,并显著降低患者血清儿茶酚胺水平,值得临床推广。%Objective To observe the effects of ivabradine tablets on cardiac function and serum catecholamine level in patients with heart failure. Methods 78 patients with heart failure admitted in the hospital between January 2015 and January 2016 were selected and divided into the study group and the control group according to random number table method, 39 cases in each group. The control group was given conventional drug therapy, while the study group was added with ivabradine tablets on the basis of the control group. The cardiac function indexes [ shoot ejection fraction ( EF ) , internal diameter of left ventricle ( LV ) ] , serum catecholamine [ noradrenaline ( NA ) , adrenaline ( Adr ) ] levels and adverse drug reactions were observed and compared between the two groups after treatment. Results After treatment, only the level of EF of the control group was significantly lower than before treatment, while the level of LV increased significantly. After treatment, EF of the study group was significantly higher than that of control group, while LV was significantly lower ( P 0. 05

  15. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A;

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  16. Thalamic GABA levels and occupational manganese neurotoxicity: Association with exposure levels and brain MRI.

    Science.gov (United States)

    Ma, Ruoyun E; Ward, Eric J; Yeh, Chien-Lin; Snyder, Sandy; Long, Zaiyang; Gokalp Yavuz, Fulya; Zauber, S Elizabeth; Dydak, Ulrike

    2017-09-02

    Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13±0.1mg/m(3); High: N=13; mean air Mn=0.23±0.18mg/m(3)), as well as unexposed control workers (N=22, mean air Mn=0.002±0.001mg/m(3)) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Pentobarbital effects on plasma catecholamines: temperature, heart rate, and blood pressure.

    Science.gov (United States)

    Baum, D; Halter, J B; Taborsky, G J; Porte, D

    1985-01-01

    The effects of intravenous pentobarbital were studied in dogs. Plasma pentobarbital concentrations were inversely related to epinephrine and norepinephrine concentrations. Plasma catecholamines appeared fully suppressed at pentobarbital levels greater than 25-30 micrograms/ml. Furthermore, pentobarbital levels were negatively related to rectal temperature, heart rate, and mean blood pressure. The methods of pentobarbital administration influenced plasma pentobarbital as well as epinephrine and norepinephrine levels, temperature, heart rate, and blood pressure. These observations suggest the possibility that pentobarbital inhibits the sympathetic nervous system, which in turn may affect temperature, heart rate, and blood pressure. Because pentobarbital anesthesia affects plasma catecholamine concentrations, the regimen used in animal models requires consideration when interpreting data potentially influenced by the sympathetic nervous system.

  18. Catecholamines in Entamoebae: recent (re)discoveries

    Indian Academy of Sciences (India)

    Dan Eichinger; Alida Coppi; Jesse Frederick; Salim Merali

    2002-11-01

    Free-living and enteric amoebae have similar two-stage life cycles, and both organisms depend on being able to monitor environmental conditions to determine whether to continue multiplying as trophozoites, or to differentiate into dormant or transmissible cysts. Conditions that support high trophozoite densities might also be expected to select for mechanisms of information exchange between these cells. We recently determined that trophozoites of at least one species of Entamoeba release and respond to catecholamine compounds during differentiation from the trophozoite stage into the cyst stage. It turns out that this is not an entirely novel finding, as a number of previous studies have demonstrated parts of this story in free-living or enteric amoebae. We briefly review here major points of the previous studies and describe some of our recent results that have extended them.

  19. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... positive correlation between frontal cortex and hippocampal BDNF levels in mice (r2=0.81, p=0.0139). Our data support the view that measures of blood and plasma BDNF levels reflect brain-tissue BDNF levels....

  20. Catecholamines and obesity: effects of exercise and training.

    Science.gov (United States)

    Zouhal, Hassane; Lemoine-Morel, Sophie; Mathieu, Marie-Eve; Casazza, Gretchen A; Jabbour, Georges

    2013-07-01

    Excess body fat in obese individuals can affect the catecholamine response to various stimuli. Indeed, several studies report lower plasma catecholamine concentrations in obese subjects compared with nonobese subjects in response to submaximal or maximal exercise. This low catecholamine response reflects decreased sympathetic nervous system (SNS) activity. Although the relationship between the SNS and obesity is not well established, some authors have suggested that low SNS activity may contribute to the development of obesity. A decreased catecholamine response could affect α- and β-adrenoceptor sensitivity in adipose tissue, reducing lipolysis and increasing fat stores. Few studies have examined the effects of obesity on the plasma catecholamine response at rest and during exercise in adolescents. It is interesting to note that the effects of age, sex, and degree of obesity and the impact of very intense exercise on the catecholamine response have not yet been well examined. Moreover, the hormonal concentrations measured in the majority of obesity studies did not take into account plasma volume changes. This methodological factor can also undoubtedly influence plasma catecholamine results.

  1. Catecholamines promote Actinobacillus pleuropneumoniae growth by regulating iron metabolism.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available Catecholamines are host stress hormones that can induce the growth of many bacteria by facilitating iron utilization and/or regulate the expression of virulence genes through specific hormone receptors. Whether these two responsive pathways are interconnected is unknown. In our previous study, it was found that catecholamines can regulate the expression of a great number of genes of Actinobacillus pleuropneumoniae, an important swine respiratory pathogen. However, bacterial growth was not affected by catecholamines in rich medium. In this study, it was discovered that catecholamines affected A. pleuropneumoniae growth in chemically defined medium (CDM. We found that serum inhibited A. pleuropneumoniae growth in CDM, while epinephrine, norepinephrine and dopamine promoted A. pleuropneumoniae growth in the CDM containing serum. The known bacterial hormone receptor QseC didn't play roles in this process. Ion-supplementation and transcriptome analysis indicated that serum addition resulted in iron-restricted conditions which were alleviated by the addition of catecholamines. Transferrin, one of the components in serum, inhibited the growth of A. pleuropneumoniae in CDM, an effect reversed by addition of catecholamines in a TonB2-dependent manner. Our data demonstrate that catecholamines promote A. pleuropneumoniae growth by regulating iron-acquisition and metabolism, which is independent of the adrenergic receptor QseC.

  2. Catecholamines promote Actinobacillus pleuropneumoniae growth by regulating iron metabolism.

    Science.gov (United States)

    Li, Lu; Chen, Zhaohui; Bei, Weicheng; Su, Zhipeng; Huang, Qi; Zhang, Liang; Chen, Huanchun; Zhou, Rui

    2015-01-01

    Catecholamines are host stress hormones that can induce the growth of many bacteria by facilitating iron utilization and/or regulate the expression of virulence genes through specific hormone receptors. Whether these two responsive pathways are interconnected is unknown. In our previous study, it was found that catecholamines can regulate the expression of a great number of genes of Actinobacillus pleuropneumoniae, an important swine respiratory pathogen. However, bacterial growth was not affected by catecholamines in rich medium. In this study, it was discovered that catecholamines affected A. pleuropneumoniae growth in chemically defined medium (CDM). We found that serum inhibited A. pleuropneumoniae growth in CDM, while epinephrine, norepinephrine and dopamine promoted A. pleuropneumoniae growth in the CDM containing serum. The known bacterial hormone receptor QseC didn't play roles in this process. Ion-supplementation and transcriptome analysis indicated that serum addition resulted in iron-restricted conditions which were alleviated by the addition of catecholamines. Transferrin, one of the components in serum, inhibited the growth of A. pleuropneumoniae in CDM, an effect reversed by addition of catecholamines in a TonB2-dependent manner. Our data demonstrate that catecholamines promote A. pleuropneumoniae growth by regulating iron-acquisition and metabolism, which is independent of the adrenergic receptor QseC.

  3. Modafinil-Induced Increases in Brain Dopamine Levels

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-04-01

    Full Text Available The acute effects of modafinil on extracellular dopamine and on dopamine transporters in the male human brain were measured by PET study in 10 healthy subjects at Brookhaven National Laboratory and National Institute on Drug Abuse, Bethesda, MD.

  4. Increased levels of carbonic anhydrase II in the developing Down syndrome brain.

    Science.gov (United States)

    Palminiello, Sonia; Kida, Elizabeth; Kaur, Kulbir; Walus, Marius; Wisniewski, Krystyna E; Wierzba-Bobrowicz, Teresa; Rabe, Ausma; Albertini, Giorgio; Golabek, Adam A

    2008-01-23

    By using a proteomic approach, we found increased levels of carbonic anhydrase II (CA II) in the brain of Ts65Dn mice, a mouse model for Down syndrome (DS). Further immunoblot analyses showed that the levels of CA II are increased not only in the brain of adult Ts65Dn mice but also in the brain of infants and young children with DS. Cellular localization of the enzyme in human brain, predominantly in the oligodendroglia and primitive vessels in fetal brain and in the oligodendroglia and some GABAergic neurons postnatally, was similar in DS subjects and controls. Given the role of CA II in regulation of electrolyte and water balance and pH homeostasis, up-regulation of CA II may reflect a compensatory mechanism mobilized in response to structural/functional abnormalities in the developing DS brain. However, this up-regulation may also have an unfavorable effect by increasing susceptibility to seizures of children with DS.

  5. Reversibility of increased formation of catecholamines in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Reisenauer, C.; Biermann, J.;

    2004-01-01

    BACKGROUND: While chronic alcohol abuse has been shown to be associated with increased production of catecholamines, little is known about the reversibility of this increased sympathetic activity and the influence of severity of alcoholic liver disease (ALD). The aim of the present study...... was to investigate whether the increase in urinary excretion rates and plasma levels of catecholamines in alcohol-abusing patients are reversible during prolonged abstinence, especially with respect to the severity of ALD. METHODS: Urinary excretion rates and plasma levels of noradrenaline (NA), adrenaline (A......) and dopamine (DA) were determined in 15 subjects with mild to moderate ALD (ALD1) and in 7 alcoholic cirrhotics (ALD2) on admission and after 2 and 12 weeks of abstinence. Eight healthy males, age-matched to ALD1, served as controls (HC). RESULTS: Urinary excretion rates (24 h) and resting plasma...

  6. Low Level Laser Therapy for Traumatic Brain Injury

    Science.gov (United States)

    2015-10-01

    recorded in each trial. A significant decrease in EL from that of first session was considered as a successful learning. Lesion size was measured in...histological sections by Image J and percentages of the lesion size was expressed relatively to the whole brain section. 6 Objective 2(ii...pinch, and muscular relaxation. After imaging, the animal was placed in the cage and allowed to recover from anesthesia. Perfusion indices were

  7. Lead poisoning: altered urinary catecholamine metabolites as indicators of intoxication in mice and children

    Energy Technology Data Exchange (ETDEWEB)

    Silbergeld, E.K. (Johns Hopkins Univ., Baltimore); Chisolm, J.J. Jr.

    1976-04-09

    Whether neuropsychological impairment occurs in children with increased lead absorption who are without clinical symptoms is of current concern. This issue, which involves potentially large numbers of children, remains unresolved, in part because of the lack of sensitive biochemical indicators of the effects of lead on the nervous system. In experimental subclinical lead poisoning in mice, significant increases in homovanillic acid and vanillylmandelic acid have been found in brain and urine. In children with increased lead absorption, these acids were measured in urine collected quantitatively under controlled dietary conditions; preliminary results show fivefold increases in the daily output of these compounds. These data suggest that the altered catecholamine metabolism also occurs in children.

  8. Effect of catecholamines and thermal exposure on lymphocyte proliferation, IL-1α & β in buffaloes

    Directory of Open Access Journals (Sweden)

    R.C. Upadhyay

    2010-02-01

    Full Text Available In order to study the effect of catecholamines (epinephrine/norepinephrine and thermal exposure on in vitro buffalo Lymphocyte Proliferation (LP apparently healthy 2- 2 1/2 years old Murrah buffalo heifers maintained as per the standard feeding and management practices were selected from Institute herd. Jugular blood was collected in the forenoon on the day of experiment and processed for Total Leucocyte Count (TLC and Differential Leucocyte Count (DLC. Lymphocyte proliferation assays were performed using whole blood and cells were incubated with epinephrine and norepinephrine (1, 1.5,2 ng/ml at 37oC with 5% CO2. Cells were counted after 72 hrs of incubation and Lymphocyte Proliferation Index (LPI was calculated. Thermal stress effect on the cultures was observed after exposure at 45oC for 4 hr after 72hrs of incubation. The cells were separated from media and media was used for analysis of IL-1α & 1β by ELISA kit. Lymphocyte proliferation Index decreased in responses to Epinephrine and Norepinephrine (P<0.01. Concentration of epinephrine and norepinephrine (1, 1.5,2 ng /ml had no distinguishable effect on LPI. IL-1α & IL-1β levels when compared with control in supernatant (exposed to 45°C were low (P<0.01 and P<0.05, respectively. There was a significant positive correlation between LPI and IL-1α (r=0.80; P<0.01 and between LPI and IL-1β (r=0.78; P<0.05. The study indicated that lymphocyte proliferation in vitro and IL-1α & β levels were affected by catecholamines and thermal exposure. Further the levels of catecholamines had significant (P<0.01 negative effect on LPI indicating that catecholamines levels modulate immunity through IL-1α and IL-1β in buffaloes.

  9. Circulating and Brain BDNF Levels in Stroke Rats. Relevance to Clinical Studies

    OpenAIRE

    Yannick Béjot; Claude Mossiat; Maurice Giroud; Anne Prigent-Tessier; Christine Marie

    2011-01-01

    BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF) levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees o...

  10. Left-sided giant adrenal myelolipoma secreting catecholamine

    Directory of Open Access Journals (Sweden)

    Sujatha Udupa

    2012-01-01

    Full Text Available Adrenal myelolipoma (AML is a rare benign tumor composed of mature adipose and hematopoietic tissue. Most of these patients are asymptomatic and the tumors are non-secreting. We present a case with a large functional adrenal myelolipoma, wherein the patient was hypertensive and biochemistry revealed increase in 24 hours urinary Vanillylmandelic Acid (VMA, a metabolite of catecholamine. The mass was removed surgically and diagnosed as adrenal myelolipoma on histopathological examination. Both his blood pressure and urinary VMA returned to normal following surgery, which suggested that the mass was functioning and was secreting catecholamine. To the best of our knowledge, a catecholamine secreting adrenal myelolipoma has been reported in the literature only once previously. The association of hypertension and adrenal myelolipoma may not be entirely coincidental, as it may be associated with secreting catecholamine, as seen in our case. We also review the literature on functioning adrenal myelolipoma.

  11. Catecholamines influence myocardial 123I MIBG uptake in neuroblastoma patients

    NARCIS (Netherlands)

    Palen, R.L.F. van der; Bulten, B.F.; Mavinkurve-Groothuis, A.M.C.; Bellersen, L.; Laarhoven, H.W.M. van; Kapusta, L.; Geus-Oei, L.F. de

    2013-01-01

    Aim: Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. Patients, methods:30 neuroblastoma patients were retrospectively assessed on cardiac

  12. Modified monolithic silica capillary for preconcentration of catecholamines

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Preconcentration of catecholamines by the modified monolithic silica in the capillary was investigated in this study. In order to achieve a microchip-based method for determining catecholamines in the saliva,the monolithic silica was fabricated in the capillary and the monolithic silica was chemically modified by on-column reaction with phenylboronate. Different modified methods were compared. The concentration conditions were optimized. This study indicates the applicability of the modified monolithic sili...

  13. Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's disease transgenic mice.

    Science.gov (United States)

    Cao, Chuanhai; Cirrito, John R; Lin, Xiaoyang; Wang, Li; Wang, Lilly; Verges, Deborah K; Dickson, Alexander; Mamcarz, Malgorzata; Zhang, Chi; Mori, Takashi; Arendash, Gary W; Holtzman, David M; Potter, Huntington

    2009-01-01

    Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain interstitial fluid and plasma without affecting Abeta elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Abeta, but also decreases in both soluble and deposited Abeta in hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels did not correlate with brain Abeta levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Abeta levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Abeta levels are not an accurate index of brain Abeta levels/deposition or cognitive performance in aged AD mice.

  14. Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

    Science.gov (United States)

    Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

    2017-01-12

    Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

  15. Acute melatonin and para-chloroamphetamine interactions on pineal, brain and serum serotonin levels as well as stress hormone levels.

    Science.gov (United States)

    Manzana, E J; Chen, W J; Champney, T H

    2001-08-03

    para-Chloroamphetamine, an amphetamine analog, alters serotonergic neurochemistry. In previous reports, melatonin (MEL), when administered with other amphetamine analogs, altered the decline in serotonin content produced by these analogs. The present studies assessed the effects of various doses of melatonin and p-chloroamphetamine on serotonin levels in numerous brain regions in male rats. Melatonin (10, 25 or 50 mg/kg, s.c.) and p-chloroamphetamine (3 or 5 mg/kg, s.c.) were administered and, 3 h later, brain samples and serum were collected. Serotonin levels in the serum and various regions of the brain were assayed using high-performance liquid chromatography. Melatonin in combination with a high dose of p-chloroamphetamine (5 mg/kg) produced cumulative deficits in serotonin levels in the serum. However, serotonin levels in the pineal, cortex or brain stem in all combined melatonin and p-chloroamphetamine groups were not significantly different from groups that received p-chloroamphetamine alone. Serum adrenocorticotropin (ACTH) and corticosterone levels were significantly elevated in the melatonin and p-chloroamphetamine combined groups, suggesting that animals receiving both treatments were more stressed than control animals or animals receiving melatonin or p-chloroamphetamine alone. These results indicate that melatonin does not alter p-chloroamphetamine-induced deficits in central serotonin levels. The increased serum adrenocorticotropic hormone, corticosterone and serotonin levels observed following melatonin and p-chloroamphetamine treatment suggest that this combination may have adverse peripheral effects.

  16. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury

    Science.gov (United States)

    Di Battista, Alex P.; Rizoli, Sandro B.; Lejnieks, Brandon; Min, Arimie; Shiu, Maria Y.; Peng, Henry T.; Baker, Andrew J.; Hutchison, Michael G.; Churchill, Nathan; Inaba, Kenji; Nascimento, Bartolomeu B.; de Oliveira Manoel, Airton Leonardo; Beckett, Andrew; Rhind, Shawn G.

    2016-01-01

    ABSTRACT Background: Acute coagulopathy after traumatic brain injury (TBI) involves a complex multifactorial hemostatic response that is poorly characterized. Objectives: To examine early posttraumatic alterations in coagulofibrinolytic, endothelial, and inflammatory blood biomarkers in relation to sympathetic nervous system (SNS) activation and 6-month patient outcomes, using multivariate partial least-squares (PLS) analysis. Patients and Methods: A multicenter observational study of 159 adult isolated TBI patients admitted to the emergency department at an urban level I trauma center, was performed. Plasma concentrations of 6 coagulofibrinolytic, 10 vascular endothelial, 19 inflammatory, and 2 catecholamine biomarkers were measured by immunoassay on admission and 24 h postinjury. Neurological outcome at 6 months was assessed using the Extended Glasgow Outcome Scale. PLS-discriminant analysis was used to identify salient biomarker contributions to unfavorable outcome, whereas PLS regression analysis was used to evaluate the covariance between SNS correlates (catecholamines) and biomarkers of coagulopathy, endotheliopathy, and inflammation. Results: Biomarker profiles in patients with an unfavorable outcome displayed procoagulation, hyperfibrinolysis, glycocalyx and endothelial damage, vasculature activation, and inflammation. A strong covariant relationship was evident between catecholamines and biomarkers of coagulopathy, endotheliopathy, and inflammation at both admission and 24 h postinjury. Conclusions: Biomarkers of coagulopathy and endotheliopathy are associated with poor outcome after TBI. Catecholamine levels were highly correlated with endotheliopathy and coagulopathy markers within the first 24 h after injury. Further research is warranted to characterize the pathogenic role of SNS-mediated hemostatic alterations in isolated TBI. PMID:27206278

  17. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia: A systematic review

    National Research Council Canada - National Science Library

    Cui, Huiru; Jin, Yi; Wang, Jijun; Weng, Xuchu; Li, Chunbo

    2012-01-01

    There is increasing interest in the role of brain-derived neurotrophic factor (BDNF) in the onset and course of schizophrenia, but there are conflicting reports about serum levels of BDNF in patients with schizophrenia...

  18. Insulin, catecholamines, glucose and antioxidant enzymes in oxidative damage during different loads in healthy humans.

    Science.gov (United States)

    Koska, J; Blazícek, P; Marko, M; Grna, J D; Kvetnanský, R; Vigas, M

    2000-01-01

    Exercise, insulin-induced hypoglycemia and oral glucose loads (50 g and 100 g) were used to compare the production of malondialdehyde and the activity of antioxidant enzymes in healthy subjects. Twenty male volunteers participated in the study. Exercise consisted of three consecutive work loads on a bicycle ergometer of graded intensity (1.5, 2.0, and 2.5 W/kg, 6 min each). Hypoglycemia was induced by insulin (Actrapid MC Novo, 0.1 IU/kg, i.v.). Oral administration of 50 g and 100 g of glucose was given to elevate plasma glucose. The activity of superoxide dismutase (SOD) was determined in red blood cells, whereas glutathione peroxidase (GSH-Px) activity was measured in whole blood. The concentration of malondialdehyde (MDA) was determined by HPLC, catecholamines were assessed radioenzymatically and glucose was measured by the glucose-oxidase method. Exercise increased MDA concentrations, GSH-Px and SOD activities as well as plasma noradrenaline and adrenaline levels. Insulin hypoglycemia increased plasma adrenaline levels, but the concentrations of MDA and the activities of GSH-Px and SOD were decreased. Hyperglycemia increased plasma MDA concentrations, but the activities of GSH-Px and SOD were significantly higher after a larger dose of glucose only. Plasma catecholamines were unchanged. These results indicate that the transient increase of plasma catecholamine and insulin concentrations did not induce oxidative damage, while glucose already in the low dose was an important triggering factor for oxidative stress.

  19. Dietary unsaturated fatty acids differently affect catecholamine handling by adrenal chromaffin cells.

    Science.gov (United States)

    Gomes, Andreia; Correia, Gustavo; Coelho, Marisa; Araújo, João Ricardo; Pinho, Maria João; Teixeira, Ana Luisa; Medeiros, Rui; Ribeiro, Laura

    2015-05-01

    Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo.

  20. Low-level laser therapy for traumatic brain injury in mice increases brain derived neurotrophic factor (BDNF) and synaptogenesis.

    Science.gov (United States)

    Xuan, Weijun; Agrawal, Tanupriya; Huang, Liyi; Gupta, Gaurav K; Hamblin, Michael R

    2015-06-01

    Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a range of brain disorders including traumatic brain injury (TBI). We (and others) have shown that applying near-infrared light to the head of animals that have suffered TBI produces improvement in neurological functioning, lessens the size of the brain lesion, reduces neuroinflammation, and stimulates the formation of new neurons. In the present study we used a controlled cortical impact TBI in mice and treated the mice either once (4 h post-TBI, 1-laser), or three daily applications (3-laser) with 810 nm CW laser 36 J/cm(2) at 50 mW/cm(2). Similar to previous studies, the neurological severity score improved in laser-treated mice compared to untreated TBI mice at day 14 and continued to further improve at days 21 and 28 with 3-laser being better than 1-laser. Mice were sacrificed at days 7 and 28 and brains removed for immunofluorescence analysis. Brain-derived neurotrophic factor (BDNF) was significantly upregulated by laser treatment in the dentate gyrus of the hippocampus (DG) and the subventricular zone (SVZ) but not in the perilesional cortex (lesion) at day 7 but not at day 28. Synapsin-1 (a marker for synaptogenesis, the formation of new connections between existing neurons) was significantly upregulated in lesion and SVZ but not DG, at 28 days but not 7 days. The data suggest that the benefit of LLLT to the brain is partly mediated by stimulation of BDNF production, which may in turn encourage synaptogenesis. Moreover the pleiotropic benefits of BDNF in the brain suggest LLLT may have wider applications to neurodegenerative and psychiatric disorders. Neurological Severity Score (NSS) for TBI mice.

  1. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.

    Science.gov (United States)

    Wang, J; Dickson, D W; Trojanowski, J Q; Lee, V M

    1999-08-01

    The abundance and solubility of Abeta peptides are critical determinants of amyloidosis in Alzheimer's disease (AD). Hence, we compared levels of total soluble, insoluble, and total Abeta1-40 and Abeta1-42 in AD brains with those in age-matched normal and pathologic aging brains using a sandwich enzyme-linked immunosorbent assay (ELISA). Since the measurement of Abeta1-40 and Abeta1-42 depends critically on the specificity of the monoclonal antibodies used in the sandwich ELISA, we first demonstrated that each assay is specific for Abeta1-40 or Abeta1-42 and the levels of these peptides are not affected by the amyloid precursor protein in the brain extracts. Thus, this sandwich ELISA enabled us to show that the average levels of total cortical soluble and insoluble Abeta1-40 and Abeta1-42 were highest in AD, lowest in normal aging, and intermediate in pathologic aging. Remarkably, the average levels of insoluble Abeta1-40 were increased 20-fold while the average levels of insoluble Abeta1-42 were increased only 2-fold in the AD brains compared to pathologic aging brains. Further, the soluble pools of Abeta1-40 and Abeta1-42 were the largest fractions of total Abeta in the normal brain (i.e., 50 and 23%, respectively), but they were the smallest in the AD brain (i.e., 2.7 and 0.7%, respectively) and intermediate (i.e., 8 and 0.8%, respectively) in pathologic aging brains. Thus, our data suggest that pathologic aging is a transition state between normal aging and AD. More importantly, our findings imply that a progressive shift of brain Abeta1-40 and Abeta1-42 from soluble to insoluble pools and a profound increase in the levels of insoluble Abeta1-40 plays mechanistic roles in the onset and/or progression of AD.

  2. Effects of altered catecholamine metabolism on pigmentation and physical properties of sclerotized regions in the silkworm melanism mutant.

    Directory of Open Access Journals (Sweden)

    Liang Qiao

    Full Text Available Catecholamine metabolism plays an important role in the determination of insect body color and cuticle sclerotization. To date, limited research has focused on these processes in silkworm. In the current study, we analyzed the interactions between catecholamines and melanin genes and their effects on the pigmentation patterns and physical properties of sclerotized regions in silkworm, using the melanic mutant melanism (mln silkworm strain as a model. Injection of β-alanine into mln mutant silkworm induced a change in catecholamine metabolism and turned its body color yellow. Further investigation of the catecholamine content and expression levels of the corresponding melanin genes from different developmental stages of Dazao-mln (mutant and Dazao (wild-type silkworm revealed that at the larval and adult stages, the expression patterns of melanin genes precipitated dopamine accumulation corresponding to functional loss of Bm-iAANAT, a repressive effect of excess NBAD on ebony, and upregulation of tan in the Dazao-mln strain. During the early pupal stage, dopamine did not accumulate in Dazao-mln, since upregulation of ebony and black genes led to conversion of high amounts of dopamine into NBAD, resulting in deep yellow cuticles. Scanning electron microscope analysis of a cross-section of adult dorsal plates from both wild-type and mutant silkworm disclosed the formation of different layers in Dazao-mln owing to lack of NADA, compared to even and dense layers in Dazao. Analysis of the mechanical properties of the anterior wings revealed higher storage modulus and lower loss tangent in Dazao-mln, which was closely associated with the altered catecholamine metabolism in the mutant strain. Based on these findings, we conclude that catecholamine metabolism is crucial for the color pattern and physical properties of cuticles in silkworm. Our results should provide a significant contribution to Lepidoptera cuticle tanning research.

  3. Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies.

    Directory of Open Access Journals (Sweden)

    Yannick Béjot

    Full Text Available BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67 was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization. CONCLUSION: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

  4. The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms.

    Science.gov (United States)

    Chen, Chuck T; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Liu, Zhen; Masoodi, Mojgan; Bazinet, Richard P

    2013-09-01

    Brain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with methyl palmoxirate (MEP). Furthermore, because other metabolic differences between DHA and EPA may also contribute to their vastly different levels, this study aimed to quantify the incorporation and turnover of DHA and EPA into brain phospholipids. Fifteen-week-old rats were subjected to vehicle or MEP prior to a 5 min intravenous infusion of (14)C-palmitate, (14)C-DHA, or (14)C-EPA. MEP reduced the radioactivity of brain aqueous fractions for (14)C-palmitate-, (14)C-EPA-, and (14)C-DHA-infused rats by 74, 54, and 23%, respectively; while it increased the net rate of incorporation of plasma unesterified palmitate into choline glycerophospholipids and phosphatidylinositol and EPA into ethanolamine glycerophospholipids and phosphatidylserine. MEP also increased the synthesis of n-3 docosapentaenoic acid (n-3 DPA) from EPA. Moreover, the recycling of EPA into brain phospholipids was 154-fold lower than DHA. Therefore, the low levels of EPA in the brain are maintained by multiple redundant pathways including β-oxidation, decreased incorporation from plasma unesterified FA pool, elongation/desaturation to n-3 DPA, and lower recycling within brain phospholipids.

  5. Treatment of idiopathic parkinsonism with L-dopa in the absence and presence of decarboxylase inhibitors: effects on plasma levels of L-dopa, dopa decarboxylase, catecholamines and 3-O-methyl-dopa.

    Science.gov (United States)

    Boomsma, F; Meerwaldt, J D; Man in't Veld, A J; Hovestadt, A; Schalekamp, M A

    1989-05-01

    The effect of levodopa (L-dopa), alone or in combination with a peripheral decarboxylase inhibitor (PDI), on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD, = dopa decarboxylase), L-dopa, 3-O-methyl-dopa (3-OMD), dopamine (DA), noradrenaline, adrenaline and dopamine beta-hydroxylase has been studied. In healthy subjects and in patients with parkinsonism plasma ALAAD level fell after administration of L-dopa + benserazide, but returned to previous levels within 90 min. In a cross-sectional study blood was obtained, 2 h after dosing, from 104 patients with idiopathic parkinsonism, divided into four groups: no L-dopa treatment (group 1), L-dopa alone (group 2), L-dopa + benserazide (Madopar) (group 3) and L-dopa + carbidopa (Sinemet) (group 4). Plasma ALAAD, which was normal in groups 1 and 2, was increased 3-fold in groups 3 and 4, indicating that there was induction of ALAAD by the co-administration of PDI. Despite this induction of ALAAD, in groups 3 and 4, with half the daily L-dopa dose compared with group 2, plasma L-dopa and 3-OMD levels were 5 times higher, while plasma DA levels were not different. The DA/L-dopa ratio was decreased 5-fold in group 2 and 16-fold in groups 3 and 4 as compared with group 1. Neither 3-OMD levels nor 3-OMD/L-dopa ratios correlated with the occurrence of on-off fluctuations. In a longitudinal study of three patients started on Madopar treatment the induction of plasma ALAAD was found to occur gradually over 3-4 weeks. Further detailed pharmacokinetic studies in plasma and cerebrospinal fluid are required in order to elucidate whether the ALAAD induction by PDI may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

  6. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, U; Bennike, B;

    2012-01-01

    Decreased levels of peripheral brain-derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness....

  7. Plasma brain natriuretic peptide levels in COPD without pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Ahmed G. El Gazzar

    2017-01-01

    Conclusion: Plasma BNP can be used as a useful prognostic biomarker of COPD and a good predictor of exacerbation, As BNP level was significantly higher in COPD patients than in control groups, (p < 0.005 and also significantly higher in grade (IV, III than grade (II and was significantly higher in grade (II than grade (I COPD patients, BNP level significantly higher (p < 0.005 during exacerbation than during remission of COPD patients.

  8. Serotonin activates catecholamine neurons in the solitary tract nucleus by increasing spontaneous glutamate inputs.

    Science.gov (United States)

    Cui, Ran Ji; Roberts, Brandon L; Zhao, Huan; Zhu, Mingyan; Appleyard, Suzanne M

    2012-11-14

    Serotonin (5-HT) is a critical neurotransmitter in the control of autonomic functions. 5-HT(3) receptors participate in vagal afferent feedback to decrease food intake and regulate cardiovascular reflexes; however, the phenotype of the solitary tract nucleus (NTS) neurons involved is not known. A(2)/C(2) catecholamine (CA) neurons in the NTS are directly activated by visceral afferents and are important for the control of food intake and cardiovascular function, making them good candidates to respond to and mediate the effects of serotonin at the level of the NTS. This study examines serotonin's effects on NTS-CA neurons using patch-clamp techniques and transgenic mice expressing an enhanced green fluorescent protein driven by the tyrosine hydroxylase (TH) promoter (TH-EGFP) to identify catecholamine neurons. Serotonin increased the frequency of spontaneous glutamate excitatory postsynaptic currents (sEPSCs) in >90% of NTS-TH-EGFP neurons, an effect blocked by the 5-HT(3) receptor antagonist ondansetron and mimicked by the 5-HT(3) receptor agonists SR5227 and mCPBG. In contrast, 5-HT(3) receptor agonists increased sEPSCs on a minority (serotonin activates NTS-TH neurons and suggest a pathway by which it can increase catecholamine release in target regions to modulate food intake, motivation, stress, and cardiovascular function.

  9. Survival and level of care among breast cancer patients with brain metastases treated with whole brain radiotherapy.

    Science.gov (United States)

    Frisk, Gabriella; Tinge, Beatrice; Ekberg, Sara; Eloranta, Sandra; Bäcklund, L Magnus; Lidbrink, Elisabet; Smedby, Karin E

    2017-08-22

    The benefit of whole brain radiotherapy (WBRT) for late stage breast cancer patients with brain metastases has been questioned. In this study we evaluated survival and level of care (hospital or home) following WBRT in a population-based cohort by personal and tumor characteristics. We identified 241 consecutive patients with breast cancer and brain metastases receiving WBRT in Stockholm, Sweden, 1999-2012. Through review of medical records, we collected data on prognostic determinants including level of care before and after WBRT. Survival was estimated using Cox regression, and odds ratios (OR) of not coming home using logistic regression. Median age at WBRT was 58 years (range 30---88 years). Most patients (n = 212, 88%) were treated with 4 Gray × 5. Median survival following WBRT was 2.9 months (interquartile range 1.1-6.6 months), and 57 patients (24%) were never discharged from hospital. Poor performance status and triple-negative tumors were associated with short survival (WHO 3-4 median survival 0.9 months, HR = 5.96 (3.88-9.17) versus WHO 0-1; triple-negative tumors median survival 2.0 months, HR = 1.87 (1.23-2.84) versus Luminal A). Poor performance status and being hospitalized before WBRT were associated with increased ORs of not coming home whereas cohabitation with children at home was protective. Survival was short following WBRT, and one in four breast cancer patients with brain metastases could never be discharged from hospital. When deciding about WBRT, WHO score, level of care before WBRT, and the patient's choice of level of care in the end-of-life period should be considered.

  10. Preliminary notes on brain weight variation across labrid fish species with different levels of cooperative behaviour

    Institute of Scientific and Technical Information of China (English)

    Marta C.SOARES; Gon(c)alo I.ANDR(E); José R.PAULA

    2015-01-01

    Brain size and weight vary tremendously in the animal kingdom.It has been suggested that brain structural development must evolve balanced between the advantages of dealing with greater social challenges and the energetic costs of maintaining and developing larger brains.Here we ask if interspecific differences in cooperative behaviour (i.e.cleaning behaviour) are related to brain weight variations in four close-related species of Labrid fish:two are obligatory cleanerfish throughout their entire life (Labroides dimidiatus and L.bicolor),one facultative cleaner fish Labropsis australis and one last species that never engage in cleaning Labrichthys unilineatus.We first search for the link between the rate of species' cooperation and its relative brain weight,and finally,if the degree of social complexity and cooperation are reflected in the weight of its major brain substructures.Overall,no differences were found in relative brain weight (in relation to body weight) across species.Fine-scale differences were solely demonstrated for the facultative cleaner L.australis,at the brainstem level.Furthermore,data visual examination indicates that the average cerebellum and brainstem weights appear to be larger for L.dimidiatus.Because variation was solely found at specific brain areas (such as cerebellum and brainstem) and not for the whole brain weight values,it suggests that species social-ecological and cognitive demands may be directly contributing to a selective investment in relevant brain areas.This study provides first preliminary evidence that links potential differences in cognitive ability in cooperative behaviour to how these may mediate the evolution of brain structural development in non-mammal vertebrate groups [Current Zoology 61 (2):274-280,2015].

  11. Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum.

    Science.gov (United States)

    Andreis, Davide Tommaso; Singer, Mervyn

    2016-09-01

    Catecholamines are endogenous neurosignalling mediators and hormones. They are integral in maintaining homeostasis by promptly responding to any stressor. Their synthetic equivalents are the current mainstay of treatment in shock states to counteract myocardial depression and/or vasoplegia. These phenomena are related in large part to decreased adrenoreceptor sensitivity and altered adrenergic signalling, with resultant vascular and cardiomyocyte hyporeactivity. Catecholamines are predominantly used in supraphysiological doses to overcome these pathological consequences. However, these adrenergic agents cause direct organ damage and have multiple 'off-target' biological effects on immune, metabolic and coagulation pathways, most of which are not monitored or recognised at the bedside. Such detrimental consequences may contribute negatively to patient outcomes. This review explores the schizophrenic 'Jekyll-and-Hyde' characteristics of catecholamines in critical illness, as they are both necessary for survival yet detrimental in excess. This article covers catecholamine physiology, the pleiotropic effects of catecholamines on various body systems and pathways, and potential alternatives for haemodynamic support and adrenergic modulation in the critically ill.

  12. Pharmacological activities of clobazam and diazepam in the rat: relation to drug brain levels.

    Science.gov (United States)

    Caccia, S; Carli, M; Garattini, S; Poggesi, E; Rech, R; Samanin, R

    1980-02-01

    Brain distribution and various pharmacological effects of clobazam and diazepam were studied in rats. When given at 10 mg/kg i.p. the compounds reached peak brain levels 15 min after injection, and showed similar half lives. At peak time brain levels were proportional to the dose administered. Very little of the N-desmethylmetabolite of each compound was found in the brain. Clobazam was less effective than diazepam in protecting rats from pentetrazol convulsions. Disrupting rota-rod performance and increasing punished responses in a "conflict" test, the relative potencies ranging from 4 to 8 in the various tests. The results are discussed in relation to the importance of animal species selection for predicting favourable therapeutic effects in humans.

  13. Caffeine suppresses β-amyloid levels in plasma and brain of Alzheimer’s transgenic mice

    OpenAIRE

    Cao, Chuanhai; Cirrito, John R.; Lin, Xiaoyang; Wang, Lilly; Verges, Deborah K.; Dickson, Alexander; Mamcarz, Malgorzata; Zhang, Chi; Mori, Takashi; Arendash, Gary W.; Holtzman, David M.; Potter, Huntington

    2009-01-01

    Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer’s Disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain β-amyloid (Aβ) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Aβ levels in both brain interstitial fluid and plasma with...

  14. Lower brain levels of serotonin in rainbow trout larvae with a propensity for social dominance

    DEFF Research Database (Denmark)

    Höglund, Erik; Åberg Andersson, Madelene

    There is general consensus that low levels of brain serotonin are associated with aggression and social dominance. However, most of the studies investigating the relationship between serotonin (5-HT) and aggressive behavior have been performed in animals with previous social experience. Studies...... performed on socially naive animals, predisposed to different levels of aggression, are needed to investigate to which extent inherited differences in 5-HTergic transmission underlie this behavioral variability. In this work we show that rainbow trout larvae, having a large yolk during emergence from...... the spawning nests, also have higher probability to become social dominant. Furthermore, newly emerged socially naïve individuals with larger yolk also had lower brain 5-HT levels. This demonstrates a propensity to social dominance, which is associated with lower brain serotonin levels, in larvae that emerge...

  15. Serum EGF and NGF levels of patients with brain injury and limb fracture

    Institute of Scientific and Technical Information of China (English)

    Yan-Feng Zhuang; Jie Li

    2013-01-01

    Objective: To explore the expression and sign if icance of human epidermal growth factor (EGF) and nerve growth factor (NGF) in patients with knee osteoarthritis. Methods: RT-PCR and enzyme-linked immunosorbent assay were used to measure the serum EGF and NGF expression levels of patients with limb fracture and brain trauma injurry after 1 d, 3 d, 7 d, 14 d and the relationship between them was analyzed. The level was compared among the simple fracture group, traumatic brain injury group and the normal control group, with 40 cases in each group. Results: The serum NGF levels were significantly different among three groups. Serum NGF, EGF mRNA and protein levels gradually decreased with the increasing injury time in the limb fracture combined with brain injury group, traumatic brain injury group, the simple fracture group and the health control group (P<0.05). Conclusions: The serum of NGF, EGF levels significantly increased when limb fracture combined with brain injury, so EGF and NGF may be involved in the process of fracture healing.

  16. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  17. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  18. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  19. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  20. Fatty Acid-Binding Protein 5 at the Blood-Brain Barrier Regulates Endogenous Brain Docosahexaenoic Acid Levels and Cognitive Function.

    Science.gov (United States)

    Pan, Yijun; Short, Jennifer L; Choy, Kwok H C; Zeng, Annie X; Marriott, Philip J; Owada, Yuji; Scanlon, Martin J; Porter, Christopher J H; Nicolazzo, Joseph A

    2016-11-16

    Fatty acid-binding protein 5 (FABP5) at the blood-brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA), a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition, the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5(+/+) and FABP5(-/-) mice using a battery of memory paradigms. FABP5(-/-) mice exhibited impaired working memory and short-term memory, and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood-brain barrier transport of DHA was assessed by measuring (14)C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5(+/+) and FABP5(-/-) mice. In line with a crucial role of FABP5 in the brain uptake of DHA, (14)C-DHA uptake into brain endothelial cells and brain capillaries of FABP5(-/-) mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%, respectively, relative to those of FABP5(+/+) mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA, and that cognitive deficits observed in FABP5(-/-) mice are associated with reduced CNS access of DHA. Genetic deletion of fatty acid-binding protein 5 (FABP5) in mice reduces uptake of exogenous docosahexaenoic acid (DHA) into brain endothelial cells and brain capillaries and reduces brain parenchymal levels of endogenous DHA. Therefore, FABP5 in the brain endothelial cell is a crucial contributor to the brain levels of DHA. Critically, lowered brain DHA levels in FABP5(-/-) mice occurred in tandem with cognitive deficits in a battery of memory paradigms. This study provides evidence of a critical role

  1. Modulation of catecholamine-synthesizing enzymes in adrenal medulla and stellate ganglia by treadmill exercise of stressed rats.

    Science.gov (United States)

    Gavrilovic, Ljubica; Spasojevic, Natasa; Dronjak, Sladjana

    2012-03-01

    The sympatho-adrenal system represents one of the main systems involved in the response to stressful events because its stress-induced activation results in an increased release of catecholamines. Exercise training acts as an important modulator of sympatho-adrenal system, adrenal medulla and stellate ganglia being two components of this system. This study aimed at investigating physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase in the adrenal medulla and stellate ganglia of chronically psychosocially stressed adult rats exposed daily to 20-min treadmill exercise for 12 weeks, using TaqMan RT-PCR assay. Chronic psychosocial stress decreased gene expression of the examined enzymes in the adrenal medulla and treadmill exercise did not lead to further modulation of the corresponding gene expression. On the other hand, chronic psychosocial stress produced a significant increase of TH (about 51%) and DBH (about 103%) gene expression in stellate ganglia, while treadmill exercise decreased gene expression of these enzymes to control levels in psychosocially stressed rats. Our data indicate that treadmill exercise leads to a decreased gene transcription of catecholamine biosynthetic enzymes in stellate ganglia and attenuation of cardiac noradrenaline production in stressful situations. Reduction of catecholamine synthesis in stellate ganglia may be linked to the beneficial effects of treadmill exercise on cardiovascular system in stressed animals.

  2. The smarter, the stronger: intelligence level correlates with brain resilience to systematic insults.

    Science.gov (United States)

    Santarnecchi, Emiliano; Rossi, Simone; Rossi, Alessandro

    2015-03-01

    Neuroimaging evidences posit human intelligence as tightly coupled with several structural and functional brain properties, also suggesting its potential protective role against aging and neurodegenerative conditions. However, whether higher order cognition might in fact lead to a more resilient brain has not been quantitatively demonstrated yet. Here we document a relationship between individual intelligence quotient (IQ) and brain resilience to targeted and random attacks, as measured through resting-state fMRI graph-theoretical analysis in 102 healthy individuals. In this modeling context, enhanced brain robustness to targeted attacks (TA) in individuals with higher IQ is supported by an increased distributed processing capacity despite the systematic loss of the most important node(s) of the system. Moreover, brain resilience in individuals with higher IQ is supported by a set of neocortical regions mainly belonging to language and memory processing network(s), whereas regions related to emotional processing are mostly responsible for lower IQ individuals. Results suggest intelligence level among the predictors of post-lesional or neurodegenerative recovery, also promoting the evolutionary role of higher order cognition, and simultaneously suggesting a new framework for brain stimulation interventions aimed at counteract brain deterioration over time.

  3. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  4. Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.

    Science.gov (United States)

    Banks, William A; Abrass, Christine K; Hansen, Kim M

    2016-01-01

    Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments.

  5. Alteration of endogenous corticosteroids and catecholamines in allergen-induced eosinophilic inflammation in Brown Norway rats

    Directory of Open Access Journals (Sweden)

    Akira Nagata

    1999-01-01

    Full Text Available Although various types of stress activate a pituitary adrenal response, the alteration of endogenous corticosteroids and catecholamines during asthma remains unclear. The aim of this study was to assess changes in endogenous corticosteroid and catecholamine levels in allergic eosinophilic inflammation in rats, using metabolic cages. Brown Norway rats (female, 6 weeks old were sensitized with intraperitoneal injections of ovalbumin on days 0 and 2 and challenged with either an aerosol of ovalbumin or saline for 30 min on day 21. Levels of urinary 11- hydroxycorticosteroid (OHCS, a primary metabolite of corticosterone; epinephrine and norepinephrine were determined in pooled samples taken 0–24 h before and 8–32 h after the challenge. Serum adrenocorticotropic hormone, corticosterone levels and cell counts in bronchoalveolar lavage fluid were assessed 32–36 h after the challenge, as well as lung eosinophil peroxidase activity, an indirect index of eosinophil infiltration. The numbers of total cells and eosinophils in bronchoalveolar lavage fluid and lung eosinophil peroxidase activity were significantly increased in the ovalbumin-challenged rats compared with the saline-challenged rats. While urinary OHCS and serum corticosterone levels were significantly increased after challenge in the ovalbumin-challenged rats, compared with the saline-challenged rats (2.1 ± 0.1 ×10−1 vs 1.7 ± 0.1 x 10−1 mg/g creatinine, P < 0.05 and 482 ± 49 vs 348 ± 19 ng/mL, P < 0.02, respectively, serum adrenocorticotropic hormone levels did not differ between the two groups. Urinary epinephrine and norepinephrine excretion also did not differ between the two groups. It is concluded that endogenous corticosterone, but not catecholamine, increases as a pathophysiologic adrenal response, possibly to protect lung during allergic eosinophilic inflammation.

  6. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    Science.gov (United States)

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (penzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  7. Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and increasing BDNF levels.

    Science.gov (United States)

    Wu, Wanqiang; Wang, Xin; Xiang, Qisen; Meng, Xu; Peng, Ye; Du, Na; Liu, Zhigang; Sun, Quancai; Wang, Chan; Liu, Xuebo

    2014-01-01

    Astaxanthin (AST) is a carotenoid pigment which possesses potent antioxidative, anti-inflammatory, and neuroprotective properties. The aim of this study was to investigate whether administration of AST had protective effects on D-galactose-induced brain aging in rats, and further examined its protective mechanisms. The results showed that AST treatment significantly restored the activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), and increased glutathione (GSH) contents and total antioxidant capacity (T-AOC), but decreased malondialdehyde (MDA), protein carbonylation and 8-hydroxy-2- deoxyguanosine (8-OHdG) levels in the brains of aging rats. Furthermore, AST increased the ratio of Bcl-2/Bax, but decreased the expression of Cyclooxygenase-2 (COX-2) in the brains of aging rats. Additionally, AST ameliorated histopathological changes in the hippocampus and restored brain derived neurotrophic factor (BDNF) levels in both the brains and hippocampus of aging rats. These results suggested that AST could alleviate brain aging, which may be due to attenuating oxidative stress, ameliorating hippocampus damage, and upregulating BDNF expression.

  8. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression

    OpenAIRE

    Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

    2015-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. Methods In this cross...

  9. Catecholamine metabolism drives generation of mitochondrial DNA deletions in dopaminergic neurons.

    Science.gov (United States)

    Neuhaus, Johannes F G; Baris, Olivier R; Hess, Simon; Moser, Natasha; Schröder, Hannsjörg; Chinta, Shankar J; Andersen, Julie K; Kloppenburg, Peter; Wiesner, Rudolf J

    2014-02-01

    Accumulation of mitochondrial DNA deletions is observed especially in dopaminergic neurons of the substantia nigra during ageing and even more in Parkinson's disease. The resulting mitochondrial dysfunction is suspected to play an important role in neurodegeneration. However, the molecular mechanisms involved in the preferential generation of mitochondrial DNA deletions in dopaminergic neurons are still unknown. To study this phenomenon, we developed novel polymerase chain reaction strategies to detect distinct mitochondrial DNA deletions and monitor their accumulation patterns. Applying these approaches in in vitro and in vivo models, we show that catecholamine metabolism drives the generation and accumulation of these mitochondrial DNA mutations. As in humans, age-related accumulation of mitochondrial DNA deletions is most prominent in dopaminergic areas of mouse brain and even higher in the catecholaminergic adrenal medulla. Dopamine treatment of terminally differentiated neuroblastoma cells, as well as stimulation of dopamine turnover in mice over-expressing monoamine oxidase B both induce multiple mitochondrial DNA deletions. Our results thus identify catecholamine metabolism as the driving force behind mitochondrial DNA deletions, probably being an important factor in the ageing-associated degeneration of dopaminergic neurons.

  10. Effect of glutathione on brain nitric oxide levels in an experimental epilepsy mouse model

    Institute of Scientific and Technical Information of China (English)

    Aylin Akcali; Sadrettin Pence; Naciye Kurtul; Mehmet Bosnak; Munife Neyal

    2009-01-01

    BACKGROUND: Oxidative stress plays an important role in the pathophysiology of epilepsy. Glutathione, known as one of the compounds of antioxidant defense, has been shown to inhibit convulsions. Nitric oxide has a proconvulsant effect on a pentylenetetrazole-induced animal model. OBJECTIVE: To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. DESIGN, TIME, AND SETTING: A randomized, controlled, animal experiment. The study was performed at the Department of Physiology, Gaziantep University and Department of Chemistry-Biochemistry, Kahramamaras Sutcu Imam University in 2006.MATERIALS: Pentylenetetrazole and glutathione were purchased from Sigma, USA. METHODS: A total of 80 mice were assigned to 8 groups (n=10): normal control, saline control (1 mL normal saline), convulsive pentylenetetrazole (single intraperitoneal administration of pentylenetetrazole, 60 mg/kg), convulsive pentylenetrazole plus glutathione (single administration of 60 mg/kg pentylenetetrazole and 200 mg/kg glutathione), five-dose glutathione (intraperitoneal injection of 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days), single-dose glutathione (single administration of 200 mg/kg glutathione), pentylenetetrazole kindling (intraperitoneal administration of pentylenetetrazole of 40 mg/kg at 1, 3, 5, 7, and 10 days), and pentylenetetrazole kindling plus glutathione group (intraperitoneal injection of 40 mg/kg pentylenetetrazole and 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days). MAIN OUTCOME MEASURES: All mice were sacrificed 1 hour after the last administration. Brain nitric oxide levels were determined by spectrophotometry. RESULTS: There were no significant differences in nitric oxide levels between the normal control, saline control, five-dose glutathione, and single-dose glutathione groups (P>0.05). Nitric oxide levels in the cerebral hemisphere and

  11. The autonomic nervous system and chromaffin tissue: neuroendocrine regulation of catecholamine secretion in non-mammalian vertebrates.

    Science.gov (United States)

    Perry, Steve F; Capaldo, Anna

    2011-11-16

    If severe enough, periods of acute stress in animals may be associated with the release of catecholamine hormones (noradrenaline and adrenaline) into the circulation; a response termed the acute humoral adrenergic stress response. The release of catecholamines from the sites of storage, the chromaffin cells, is under neuroendocrine control, the complexity of which appears to increase through phylogeny. In the agnathans, the earliest branching vertebrates, the chromaffin cells which are localized predominantly within the heart, lack neuronal innervation and thus catecholamine secretion in these animals is initiated solely by humoral mechanisms. In the more advanced teleost fish, the chromaffin cells are largely confined to the walls of the posterior cardinal vein at the level of the head kidney where they are intermingled with the steroidogenic interrenal cells. Catecholamine secretion from teleost chromaffin cells is regulated by a host of cholinergic and non-cholinergic pathways that ensure sufficient redundancy and flexibility in the secretion process to permit synchronized responses to a myriad of stressors. The complexity of catecholamine secretion control mechanisms continues through the amphibians, reptiles and birds although neural (cholinergic) regulation may become increasingly important in birds. Discrete adrenal glands are present in the non-mammalian tetrapods but unlike in mammals, there is no clear division of a steroidogenic cortex and a chromaffin cell enriched medulla. However, in all groups, there is an obvious intermingling of chromaffin and steroiodogenic cells. The association of the two cell types may be particularly important in the amphibians and birds because like in mammals, the enzyme catalysing the methylation of noradrenaline to adrenaline, PNMT, is under the control of the steroid cortisol.

  12. REM sleep loss associated changes in orexin-A levels in discrete brain areas in rats.

    Science.gov (United States)

    Mehta, Rachna; Khanday, Mudasir Ahmad; Mallick, Birendra Nath

    2015-03-17

    Rapid eye movement sleep (REMS) serves house-keeping function of the brain and its loss affects several pathophysiological processes. Relative levels of neurotransmitters including orexin A (Orx-A) in various parts of the brain in health and diseases are among the key factors for modulation of behaviors, including REMS. The level of neurotransmitter in an area in the brain directly depends on number of projecting neurons and their firing rates. The locus coeruleus (LC), the site of REM-OFF neurons, receives densest, while the pedunculo-pontine area (PPT), the site of REM-ON neurons receives lesser projections from the Orx-ergic neurons. Further, the Orx-ergic neurons are active during waking and silent during REMS and NREMS. Therefore, the level of Orx-A in discrete regions of the brain is likely to be different during normal and altered states, which in turn is likely to be responsible for altered behaviors in health and diseases, including in relation to REMS. Therefore, in the present study, we estimated Orx-A level in LC, cortex, posterior hypothalamus (PH), hippocampus, and PPT after 96 h REMSD, in post-deprivation recovered rats and in control rats. This is the first report of estimation of Orx-A in different brain regions after prolonged REMSD. It was observed that after REMSD the Orx-A level increased significantly in LC, cortex and PH which returned to normal level after recovery; however, the level did not change in the hippocampus and PPT. The Orx-A induced modulation of REMS could be secondary to increased waking.

  13. Level set method with automatic selective local statistics for brain tumor segmentation in MR images.

    Science.gov (United States)

    Thapaliya, Kiran; Pyun, Jae-Young; Park, Chun-Su; Kwon, Goo-Rak

    2013-01-01

    The level set approach is a powerful tool for segmenting images. This paper proposes a method for segmenting brain tumor images from MR images. A new signed pressure function (SPF) that can efficiently stop the contours at weak or blurred edges is introduced. The local statistics of the different objects present in the MR images were calculated. Using local statistics, the tumor objects were identified among different objects. In this level set method, the calculation of the parameters is a challenging task. The calculations of different parameters for different types of images were automatic. The basic thresholding value was updated and adjusted automatically for different MR images. This thresholding value was used to calculate the different parameters in the proposed algorithm. The proposed algorithm was tested on the magnetic resonance images of the brain for tumor segmentation and its performance was evaluated visually and quantitatively. Numerical experiments on some brain tumor images highlighted the efficiency and robustness of this method.

  14. A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue.

    Science.gov (United States)

    Takatori, T; Tomii, S; Terazawa, K; Nagao, M; Kanamori, M; Tomaru, Y

    1991-01-01

    The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860-0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples.

  15. The Effect of Hemoglobin Levels on Mortality in Pediatric Patients with Severe Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kevin F. Yee

    2016-01-01

    Full Text Available Objective. There is increasing evidence of adverse outcomes associated with blood transfusions for adult traumatic brain injury patients. However, current evidence suggests that pediatric traumatic brain injury patients may respond to blood transfusions differently on a vascular level. This study examined the influence of blood transfusions and anemia on the outcome of pediatric traumatic brain injury patients. Design. A retrospective cohort analysis of severe pediatric traumatic brain injury (TBI patients was undertaken to investigate the association between blood transfusions and anemia on patient outcomes. Measurements and Main Results. One hundred and twenty patients with severe traumatic brain injury were identified and included in the analysis. The median Glasgow Coma Scale (GCS was 6 and the mean hemoglobin (Hgb on admission was 115.8 g/L. Forty-three percent of patients (43% received at least one blood transfusion and the mean hemoglobin before transfusion was 80.1 g/L. Multivariable regression analysis revealed that anemia and the administration of packed red blood cells were not associated with adverse outcomes. Factors that were significantly associated with mortality were presence of abusive head trauma, increasing PRISM score, and low GCS after admission. Conclusion. In this single centre retrospective cohort study, there was no association found between anemia, blood transfusions, and hospital mortality in a pediatric traumatic brain injury patient population.

  16. Circadian variations of catecholamines and blood pressure in patients with pseudohypoparathyroidism and hypertension.

    Science.gov (United States)

    Brickman, A S; Stern, N; Sowers, J R

    1990-01-01

    The relationship between 24-h recumbent blood pressure levels and secretory patterns of catecholamines was investigated in 4 patients with pseudohypoparathyroidism (PsHP) and hypertension and in 9 patients with essential hypertension. A clear circadian rhythm of blood pressure and catecholamines was documented in both groups with lowest levels of blood pressures and catecholamines occurring during sleep. During the 24-h period of recumbency mean arterial blood pressure (MAP) was correlated (r = 0.63, p less than or equal to 0.01) with plasma norepinephrine (N) in the patients with essential hypertension, but this correlation was weaker in patients with PsHP (r = 0.38, p less than or equal to 0.05). MAP was more closely related to plasma epinephrine (E) (r = 0.62, p less than or equal to 0.01) than to plasma NE in patients with PsHP. Plasma NE and E levels were considerably lower in patients with PsHP than in patients with essential hypertension throughout the 24-h recumbent period. The sleep-related decline in blood pressure and NE was less than in patients with essential hypertension. These results suggest that while the sympathetic nervous system may have a role in hour-to-hour maintenance of blood pressure in patients with PsHP and hypertension, it does not appear to be responsible for the elevated arterial pressure in these patients. Factors other than those investigated, such as obesity, alterations in sodium homeostasis of refractoriness of the vascular smooth muscle to the vasodilatory effect of PTH may be involved in the pathogenesis of hypertension in PsHP.

  17. LORRY DRIVERS WORK STRESS EVALUATED BY CATECHOLAMINES EXCRETED IN URINE

    NARCIS (Netherlands)

    VANDERBEEK, AJ; MEIJMAN, TF; FRINGSDRESEN, MHW; KUIPER, JI

    1995-01-01

    Objectives-To evaluate lorry drivers' work stress by measurement of adrenaline and noradrenaline excreted in the urine, and to find out which factors in their working situation are related to the excretion rates of these catecholamines. Methods-The urinary excretion of adrenaline and noradrenaline o

  18. LORRY DRIVERS WORK STRESS EVALUATED BY CATECHOLAMINES EXCRETED IN URINE

    NARCIS (Netherlands)

    VANDERBEEK, AJ; MEIJMAN, TF; FRINGSDRESEN, MHW; KUIPER, JI

    Objectives-To evaluate lorry drivers' work stress by measurement of adrenaline and noradrenaline excreted in the urine, and to find out which factors in their working situation are related to the excretion rates of these catecholamines. Methods-The urinary excretion of adrenaline and noradrenaline

  19. 21 CFR 862.1165 - Catecholamines (total) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  20. Brain glycogen – new perspectives on its metabolic function and regulation at the subcellular level

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    Linea Frimodt Obel

    2012-03-01

    Full Text Available Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g. liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies – it is a highly dynamic molecule with versatile implications in brain function, i.e. synaptic activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms underlying glycogen metabolism. Based on i the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP, ii alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and iii a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g. turnover is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology.

  1. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

    Directory of Open Access Journals (Sweden)

    Fuka Aizawa

    2016-12-01

    Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

  2. Effects of anesthetic agents on brain blood oxygenation level revealed with ultra-high field MRI.

    Directory of Open Access Journals (Sweden)

    Luisa Ciobanu

    Full Text Available During general anesthesia it is crucial to control systemic hemodynamics and oxygenation levels. However, anesthetic agents can affect cerebral hemodynamics and metabolism in a drug-dependent manner, while systemic hemodynamics is stable. Brain-wide monitoring of this effect remains highly challenging. Because T(2*-weighted imaging at ultra-high magnetic field strengths benefits from a dramatic increase in contrast to noise ratio, we hypothesized that it could monitor anesthesia effects on brain blood oxygenation. We scanned rat brains at 7T and 17.2T under general anesthesia using different anesthetics (isoflurane, ketamine-xylazine, medetomidine. We showed that the brain/vessels contrast in T(2*-weighted images at 17.2T varied directly according to the applied pharmacological anesthetic agent, a phenomenon that was visible, but to a much smaller extent at 7T. This variation is in agreement with the mechanism of action of these agents. These data demonstrate that preclinical ultra-high field MRI can monitor the effects of a given drug on brain blood oxygenation level in the absence of systemic blood oxygenation changes and of any neural stimulation.

  3. Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety

    NARCIS (Netherlands)

    Molendijk, Marc L.; Bus, Boudewijn A. A.; Spinhoven, Philip; Penninx, Brenda W. J. H.; Prickaerts, Jos; Voshaar, Richard C. Oude; Elzinga, Bernet M.

    2012-01-01

    Objectives. Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as compare

  4. Fractal Analysis of Brain Blood Oxygenation Level Dependent (BOLD) Signals from Children with Mild Traumatic Brain Injury (mTBI)

    Science.gov (United States)

    Dona, Olga; DeMatteo, Carol; Connolly, John F.

    2017-01-01

    Background Conventional imaging techniques are unable to detect abnormalities in the brain following mild traumatic brain injury (mTBI). Yet patients with mTBI typically show delayed response on neuropsychological evaluation. Because fractal geometry represents complexity, we explored its utility in measuring temporal fluctuations of brain resting state blood oxygen level dependent (rs-BOLD) signal. We hypothesized that there could be a detectable difference in rs-BOLD signal complexity between healthy subjects and mTBI patients based on previous studies that associated reduction in signal complexity with disease. Methods Fifteen subjects (13.4 ± 2.3 y/o) and 56 age-matched (13.5 ± 2.34 y/o) healthy controls were scanned using a GE Discovery MR750 3T MRI and 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 35/2000ms), acquired over 6 minutes. Motion correction was performed and anatomical and functional images were aligned and spatially warped to the N27 standard atlas. Fractal analysis, performed on grey matter, was done by estimating the Hurst exponent using de-trended fluctuation analysis and signal summation conversion methods. Results and Conclusions Voxel-wise fractal dimension (FD) was calculated for every subject in the control group to generate mean and standard deviation maps for regional Z-score analysis. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels (3.05% over the brain) were eliminated from subsequent analysis. For each mTBI patient, regions where Z-score values were at least 2 standard deviations away from the mean (i.e. where |Z| > 2.0) were identified. In individual patients the frequently affected regions were amygdala (p = 0.02), vermis(p = 0.03), caudate head (p = 0.04), hippocampus(p = 0.03), and hypothalamus(p = 0.04), all previously reported as dysfunctional after mTBI, but based on group analysis. It is well known that the brain is best modeled as a complex

  5. Effect of clozapine and molindone on plasma and brain levels of mescaline in mice.

    Science.gov (United States)

    Shah, N S; Gulati, O D

    1984-01-01

    Levels of unchanged mescaline were examined in the plasma and brain of albino Swiss-Webster mice pretreated with various doses of either clozapine or molindone. In clozapine treated mice, the mescaline levels were statistically significantly higher at 2 and 3 h with 7.5 and 15.0 mg/kg and at 1, 2 and 3 h with 30 mg/kg. Molindone at 4.0 and 8.0 mg/kg produced no significant effect; at 16.0 and 48.0 mg/kg, the levels were significantly higher at 1 and 2 h. Elevated brain levels of mescaline by clozapine and molindone indicate an adverse metabolic interaction between a hallucinogen and drugs that are commonly used to treat mescaline-induced psychosis.

  6. Significance of CT findings and catecholamine determination in peripheral blood of asymptomatic pheochromocytoma and paraganglioma

    Energy Technology Data Exchange (ETDEWEB)

    Saginoya, Toshiyuki; Miyake, Hidetoshi; Kiyosue, Hiro; Okahara, Mika; Hori, Yuko; Hata, Hiroyuki; Mori, Hiromu [Oita Medical Univ., Hasama (Japan)

    2001-01-01

    The purpose of this study was to assess the CT findings and significance of hormone determination in the peripheral blood of asymptomatic patients with pheochromocytoma and paraganglioma. CT findings in 29 patients with surgically proven pheochromocytoma (n=19) and paraganglioma (n=10) were reviewed. Nine patients (31%) were symptomatic and 20 (69%) were asymptomatic. Tumor size ranged from 39 mm to 114 mm (mean: 60 mm) in symptomatic patients and 11 mm to 100 mm (mean: 50 mm) in asymptomatic ones. Of the 9 symptomatic patients and 18 asymptomatic patients, a homogeneous solid pattern was seen in 4 and 4, mixed pattern in 2 and 6, and massive necrotic pattern in 3 and 8 patients, respectively, on CT scans. The CT attenuation values in symptomatic cases ranged from 30 HU to 50 HU (mean: 41 HU) on precontrast CT scans and 60 HU to 111 HU (mean: 77 HU) on postcontrast CT scans, while those in asymptomatic cases ranged from 15 HU to 48 HU (mean: 33 HU) on precontrast CT scans and 66 HU to 133 HU (mean: 95 HU) on postcontrast CT scans. There were no statistically significant differences in tumor size, homogeneity, or CT attenuation values between symptomatic and asymptomatic patients. All symptomatic patients and 17 (89%) of 19 asymptomatic cases showed elevated levels of catecholamine (epinephrine) or norepinephrine in the peripheral blood. Our study showed that the CT findings in asymptomatic patients were similar to those in symptomatic patients, and 89% of asymptomatic patients showed elevation of catecholamine in the peripheral blood. Determination of catecholamine level in the peripheral blood is recommended for preoperative diagnosis in patients suspected of having asymptomatic phenochromocytoma or paraganglioma on CT scans. (author)

  7. Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis.

    Science.gov (United States)

    Hamelink, Carol; Tjurmina, Olga; Damadzic, Ruslan; Young, W Scott; Weihe, Eberhard; Lee, Hyeon-Woo; Eiden, Lee E

    2002-01-08

    The adrenal gland is important for homeostatic responses to metabolic stress: hypoglycemia stimulates the splanchnic nerve, epinephrine is released from adrenomedullary chromaffin cells, and compensatory glucogenesis ensues. Acetylcholine is the primary neurotransmitter mediating catecholamine secretion from the adrenal medulla. Accumulating evidence suggests that a secretin-related neuropeptide also may function as a transmitter at the adrenomedullary synapse. Costaining with highly specific antibodies against the secretin-related neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and the vesicular acetylcholine transporter (VAChT) revealed that PACAP is found in nerve terminals at all mouse adrenomedullary cholinergic synapses. Mice with a targeted deletion of the PACAP gene had otherwise normal cholinergic innervation and morphology of the adrenal medulla, normal adrenal catecholamine and blood glucose levels, and an intact initial catecholamine secretory response to insulin-induced hypoglycemia. However, insulin-induced hypoglycemia was more profound and longer-lasting in PACAP knock-outs, and was associated with a dose-related lethality absent in wild-type mice. Failure of PACAP-deficient mice to adequately counterregulate plasma glucose levels could be accounted for by impaired long-term secretion of epinephrine, secondary to a lack of induction of tyrosine hydroxylase, normally occurring after insulin hypoglycemia in wild-type mice, and a consequent depletion of adrenomedullary epinephrine stores. Thus, PACAP is needed to couple epinephrine biosynthesis to secretion during metabolic stress. PACAP appears to function as an "emergency response" cotransmitter in the sympathoadrenal axis, where the primary secretory response is controlled by a classical neurotransmitter but sustained under paraphysiological conditions by a neuropeptide.

  8. Electrical activity of the visual cortex under conditions of change in the levels of monoamines in the brain of animals.

    Science.gov (United States)

    Borob'ev, V V; Gal'chenko, A A; Deryugina, O N

    1991-01-01

    The changes in the electrograms of the visual cortex of awake animals under the influence of light stimulation in conditions of a pharmacological effect on the monoamine (MA) systems of the brain were investigated in experiments on 8 rabbits and 12 rats. The following was found following the administration of MA precursors (5-hydroxytryptophan and d,l-dihydroxyphenylalanine): a) a decrease in the amplitude of the averaged evoked potentials in response to rhythmical light stimuli (1-20 pulses/sec); b) intensification of rapid (15-25 Hz) oscillations in the spontaneous electrical activity of the cortex, as well as attenuation and modification of the effects of the blocker of MA synthesis, a-methyl-dihydroxyphenylalanine. A potentiation of the MA precursors was observed with light stimulation in the frequency spectra of the electrocorticograms. The specific characteristics of the action of the catecholamine precursor were manifested in the same conditions in the form of an intensification of the power of the 5-7 Hz rhythms, and an attenuation of the power of the 2-3 Hz rhythms.

  9. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

    OpenAIRE

    Shin, Andrew C.; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A.; Zielinski, Elizabeth; Zhou, Jian-Ying; Scherer, Thomas; Lindtner, Claudia; Phillip J White; Lapworth, Amanda L.; Ilkayeva, Olga; Knippschild, Uwe; Wolf, Anna M.; Scheja, Ludger; Grove, Kevin L.

    2014-01-01

    Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α keto-acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors ...

  10. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    Science.gov (United States)

    Zhang, Yiting; Hodgson, Nathaniel W; Trivedi, Malav S; Abdolmaleky, Hamid M; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

  11. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Yiting Zhang

    Full Text Available Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl exists in multiple forms, including methylcobalamin (MeCbl and adenosylcobalamin (AdoCbl, serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age, primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY. Low levels of the antioxidant glutathione (GSH have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

  12. Automated ventricular systems segmentation in brain CT images by combining low-level segmentation and high-level template matching

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    Ward Kevin R

    2009-11-01

    Full Text Available Abstract Background Accurate analysis of CT brain scans is vital for diagnosis and treatment of Traumatic Brain Injuries (TBI. Automatic processing of these CT brain scans could speed up the decision making process, lower the cost of healthcare, and reduce the chance of human error. In this paper, we focus on automatic processing of CT brain images to segment and identify the ventricular systems. The segmentation of ventricles provides quantitative measures on the changes of ventricles in the brain that form vital diagnosis information. Methods First all CT slices are aligned by detecting the ideal midlines in all images. The initial estimation of the ideal midline of the brain is found based on skull symmetry and then the initial estimate is further refined using detected anatomical features. Then a two-step method is used for ventricle segmentation. First a low-level segmentation on each pixel is applied on the CT images. For this step, both Iterated Conditional Mode (ICM and Maximum A Posteriori Spatial Probability (MASP are evaluated and compared. The second step applies template matching algorithm to identify objects in the initial low-level segmentation as ventricles. Experiments for ventricle segmentation are conducted using a relatively large CT dataset containing mild and severe TBI cases. Results Experiments show that the acceptable rate of the ideal midline detection is over 95%. Two measurements are defined to evaluate ventricle recognition results. The first measure is a sensitivity-like measure and the second is a false positive-like measure. For the first measurement, the rate is 100% indicating that all ventricles are identified in all slices. The false positives-like measurement is 8.59%. We also point out the similarities and differences between ICM and MASP algorithms through both mathematically relationships and segmentation results on CT images. Conclusion The experiments show the reliability of the proposed algorithms. The

  13. Role of Catecholamine in Tumor Angiogenesis Linked to Capacitance Relaxation Phenomenon

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    Guangyue SHI

    2010-08-01

    Full Text Available The present paper deals with the CgA level during metastasis linked with Capacitance relaxation phenomenon in cancer cell. CgA co-stored and correlated by exocytosis with catecholamines is a precursor to peptides that exert feedback regulatory control on catecholamine secretion. It is to be noted that CgA was the most sensitive marker for detecting patients with tumor angiogenesis. The progressive rise in CgA increases with the tumor size and this fact has been correlated with the Capacitance relaxation phenomenon (T. K. Basak, US patent No. 5691178, 1997 in different stages. The experimental results of Capacitance relaxation phenomenon were given as inputs to a model for correlation with the CgA level. This model is a control system model, the output of which is the CgA level. It is to be noted that the model is simulated in MATLAB. The expression of tumorogenisis in prostate and liver is also linked to Capacitance relaxation phenomenon in respect of its correlation with the CgA level.

  14. MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels.

    Science.gov (United States)

    Oien, Derek B; Osterhaus, Greg L; Latif, Shaheen A; Pinkston, Jonathan W; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C; Moskovitz, Jackob

    2008-07-15

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA(-/-)) mouse. Here we show that MsrA(-/-) mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA(-/-) mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA(-/-) mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA(-/-) brains contained significantly higher levels of dopamine up to 12 months of age, while lower levels of dopamine were observed at 16 months of age. Moreover, striatal regions of MsrA(-/-) mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathways are impaired in MsrA(-/-) mice, which may contribute to their abnormal behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress.

  15. The MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels

    Science.gov (United States)

    Oien, Derek B.; Osterhaus, Greg L.; Latif, Shaheen A.; Pinkston, Jonathan W.; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C.; Moskovitz, Jackob

    2008-01-01

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA−/−) mouse. Here we show that MsrA−/− mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA−/− mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA−/− mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA−/− brains contained significantly higher levels of dopamine up to 12 months of age, while lower level of dopamine was observed at 16 months of age. Moreover, striatal regions of MsrA−/− mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathway are impaired in MsrA−/− mice, which may contribute to their abnormal bio-behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress. PMID:18466776

  16. Opiate-induced changes in brain adenosine levels and narcotic drug responses.

    Science.gov (United States)

    Wu, M; Sahbaie, P; Zheng, M; Lobato, R; Boison, D; Clark, J D; Peltz, G

    2013-01-01

    We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10-40 mg/kg) administered over a 4-day period selectively induced a twofold decrease (pOpiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal.

  17. Brain and hepatic Hsp70 protein levels in heat-acclimated broiler chickens during heat stress

    Directory of Open Access Journals (Sweden)

    EN Guerreiro

    2004-12-01

    Full Text Available In the present study we have investigated the effects of heat acclimation on brain and hepatic Hsp70 protein levels and body temperature of broiler chickens in response to gradual heat stress. Two groups of broilers were raised up to 47 days of age under distinct temperature conditions: thermoneutral (TN, according to bird age or hot environmental (HS, 31-33°C. At 46 days of age, the birds reared at high ambient temperature were transferred to thermoneutrality conditions. After 18 h, these birds and the birds reared at thermoneutral temperature were submitted to gradual heat stress in a climatic chamber so that environment temperature was increased from 28 to 40ºC at a rate of 2ºC/h. Colonic temperature was measured using a thermometer sensor probe at each two hours, and hepatic and brain tissues were collected immediately after slaughter in order to assess Hsp70 protein level by Western blotting analysis. The colonic temperatures of birds reared at high temperature increased steeply during the first 2 h of heat stress (1.06ºC/h and more slowly thereafter (0.59ºC/h. Broilers reared at thermoneutral temperature showed a small increase in the first 4 h of heat stress (0.18ºC/h and then colonic temperature increased sharply (0.72ºC/h. Nevertheless, both groups presented similar final colonic temperature by the end of the stress period. Hsp70 levels (ng Hsp70 µg total protein-1 did not change in the liver or brain of the birds reared at high temperature. On the other hand, both liver and brain Hsp70 levels increased significantly during heat stress in the animals reared at thermoneutrality, with a higher expression of this peptide in brain tissue.

  18. Nonparallel changes in brain monoamines of pyridoxine-deficient growing rats.

    Science.gov (United States)

    Dakshinamurti, K; LeBlancq, W D; Herchl, R; Havlicek, V

    1976-11-23

    The effects of a large number of neurotropic drugs have been attributed to changes in the metabolism of 5-hydroxytryptamine. The aromatic amino acid decarboxylase considered to decarboxylate both dihydroxyphenylalanine and 5-hydroxytryptophan requires pyridoxal phosphate as coenzyme. Thus, in pyridoxine deficiency one would expect a decrease of serotonin as well as the catecholamines of the brain. In the present study we have found a very significant decrease in brain serotonin of the pyridoxine-deficient growing rat. However, the brain levels of norepinephrine and dopamine were not altered. This decrease in serotonin does not result from a decrease either in the brain level of trytophan or the activity of tryptophan hydroxylase. Increased degradation of serotonin measured by the levels of its metabolite, 5-hydroxyindoleacetic acid is also excluded, thus suggesting the possibility that the decarboxylation of 5-hydroxytryptophan is decreased in pyridoxine deficiency.

  19. Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis.

    Science.gov (United States)

    Aguilera, A; Selgas, R; Codoceo, R; Bajo, A

    2000-01-01

    Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

  20. Elevated levels of a glycoprotein antigen (P-80) in gray and white matter of brain from victims of multiple sclerosis.

    Science.gov (United States)

    Cruz, T F; Quackenbush, E J; Letarte, M; Moscarello, M A

    1986-06-01

    The levels of a glycoprotein reactive with monoclonal antibody (MAb) 44D10 in white and gray matter from brains of victims of several neurological diseases, including Multiple Sclerosis, Alzheimer's, Parkinson's and Huntington's diseases, were compared to that of normal individuals. The concentration of antigen reactive with MAb 44D10 was elevated in both gray and white matter of all MS brains examined, but not in brains with other neurological diseases. The increase in the concentration of antigen varied amongst the MS brains, such that the levels of antigen were only slightly increased in 2 of the 6 MS brains whereas 2 to 4 fold higher levels were found in the other 4 brains. Increased levels of antigen were detected in gray matter of MS brains, whereas this antigen was either not detected or present in very low levels in gray matter homogenates prepared from age-matched normal brains. MAb Leu 1, which reacts with T lymphocytes, was not absorbed by normal and MS brain tissue suggesting the increase in antigen reactive with MAb 44D10 in MS brain homogenates was not associated with non-specific infiltration by T lymphocytes. Comparison of the purified antigen from MS gray matter and normal white matter by gel electrophoresis demonstrated that MAb 44D10 was reacting with a similar protein in both tissues with an apparent molecular weight of 80K. We have named this molecule P-80 glycoprotein.

  1. [Asymmetry of the bioelectrical activity of the human brain at different levels of consciousness].

    Science.gov (United States)

    Rusalova, M N

    2006-12-01

    Asymmetry of different human EEG indices was studied at different levels of consciousness. Subjects' self-reported changes in the content of consciousness: the intensity and quality of involuntary mental processes served as indicator of the level of consciousness. It was shown that a certain profile of EEG asymmetry corresponded to each the observed level of consciousness. In active state of consciousness, the connections in the high-frequency bands: beta-2 and gamma, were more pronounced in the left hemisphere of the brain. At the same time, transition of the focus of coherent connections to the right hemisphere was characteristic of the state of inhibition of "internal speech". The interhemisphere dynamics of autospectra amplitude and foci of coherent connections supports the notion that the character of interhemisphere asymmetry of the brain bioelectrical activity depends on its functional state.

  2. Genetic increase in brain-derived neurotrophic factor levels enhances learning and memory.

    Science.gov (United States)

    Nakajo, Yukako; Miyamoto, Susumu; Nakano, Yoshikazu; Xue, Jing-Hui; Hori, Takuya; Yanamoto, Hiroji

    2008-11-19

    Brain-derived neurotrophic factor (BDNF), a neurotrophin, is known to promote neuronal differentiation stimulating neurite outgrowth in the developing CNS, and is also known to modulate synaptic plasticity, thereby contributing to learning and memory in the mature brain. Here, we investigated the role of increased levels of intracerebral BDNF in learning and memory function. Using genetically engineered transgenic BDNF overexpressing mice (RTG-BDNF), young adult, homozygous (+/+), heterozygous (+/-), or wild-type (-/-) littermates, we analyzed escape latency to a hidden-platform and swimming velocity in the Morris Water Maze test (MWM) with modifications for the mice. The MWM comprised 4 trials per day over 5 consecutive days (sessions) without prior or subsequent training. In a separate set of animals, BDNF protein levels in the cortex, thalamostriatum and the hippocampus were measured quantitatively using ELISA. In the BDNF (+/-) mice, the BDNF levels in the cortex, the thalamostriatum and the hippocampus were significantly high, compared to the wild-type littermates; 238%, 158%, and 171%, respectively (PBDNF levels in the BDNF (+/+) mice were not elevated. The BDNF (+/-), but not the (+/+) mice, demonstrated significantly shorter escape latency, shorter total path length in the MWM, and more frequent arrivals at the location where the platform had been placed previously in the probe trial, compared with the wild-type littermates (PBDNF-transgenic mice, increased BDNF levels in the brain were found to enhance spatial learning and memory function. Although it has been postulated that excessive BDNF is deteriorating for neuronal survival or neurite outgrowth, further investigations are needed to clarify the mechanism of paradoxical lack of increase in BDNF levels in the (+/+) mouse brain.

  3. Catecholamines in plasma from artery, cubital vein, and femoral vein in patients with cirrhosis. Significance of sampling site

    DEFF Research Database (Denmark)

    Henriksen, J H; Ring-Larsen, H; Christensen, N J

    1986-01-01

    The concentration of noradrenaline (NA) and adrenaline (A) was measured in arterial, cubital venous and femoral venous plasma in order to determine possible differences in different vascular beds in the peripheral circulation. In patients with cirrhosis, arterial plasma NA (median 2.54 nmol/l, n ...... the skin of forearm and hand). To assess circulating levels of catecholamines, the importance of arterial sampling is stressed as peripheral venous samples may also reflect local factors....

  4. Increased Arousal Levels and Decreased Sleep by Brain Music in Rats

    Institute of Scientific and Technical Information of China (English)

    Guang-Zhan Fang; Chun-Peng Zhang; Dan Wu; Yang Xia; Yong-Xiu Lai; De-Zhong Yao

    2009-01-01

    More and more studies have been reported on whether music and other types of auditory stimulation would improve the quality of sleep.Many of these studies have found significant results,but others argue that music is not significantly better than the tones or control conditions in improving sleep.For further understanding the relationship between music and sleep or music and arousal,the present study therefore examines the effects of brain music on sleep and arousal by means of biofeedback.The music is from the transformation of rapid eye movement (REM) sleep electroencephalogram (EEG) of rats using an algorithm in the Chengdu Brain Music (CBM) system.When the brain music was played back to rats,EEG data were recorded to assess the efficacy of music to induce or improve sleep,or increase arousal levels by sleep staging,etc.Our results demonstrate that exposure to the brain music increases arousal levels and decreases sleep in rats,and the underlying mechanism of decreased non-rapid eye movement (NREM) and REM sleep may be different.

  5. Reduced serum levels of oestradiol and brain derived neurotrophic factor in both diabetic women and HFD-feeding female mice.

    Science.gov (United States)

    Zhang, Yi; Zhang, Shan-Wen; Khandekar, Neeta; Tong, Shi-Fei; Yang, He-Qin; Wang, Wan-Ru; Huang, Xu-Feng; Song, Zhi-Yuan; Lin, Shu

    2017-04-01

    The estrogen levels in the pre and post menstrual phases interact with brain-derived neurotrophic factor in a complex manner, which influences the overall state of the body. To study the role of oestradiol and brain-derived neurotrophic factor in modulating obesity related type 2 diabetes and the interactions between two factors, we enrolled 15 diabetic premenopausal women and 15 diabetic postmenopausal women respectively, the same number of healthy pre and postmenopausal women were recruited as two control groups. The fasting blood glucose, insulin, lipids, estrogen, and brain-derived neurotrophic factor levels were measured through clinical tests. Additionally, we set up obese female mouse model to mimic human trial stated above, to verify the relationship between estrogen and brain-derived neurotrophic factor. Our findings revealed that there is a moderately positive correlation between brain-derived neurotrophic factor and oestradiol in females, and decreased brain-derived neurotrophic factor may worsen impaired insulin function. The results further confirmed that high fat diet-fed mice which exhibited impaired glucose tolerance, showed lower levels of oestradiol and decreased expression of brain-derived neurotrophic factor mRNA in the ventromedial hypothalamus. The level of brain-derived neurotrophic factor reduced on condition that the level of oestradiol is sufficiently low, such as women in postmenopausal period, which aggravates diabetes through feeding-related pathways. Increasing the level of brain-derived neurotrophic factor may help to alleviate the progression of the disease in postmenopausal women with diabetes.

  6. Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle.

    Science.gov (United States)

    Albert, Kimberly; Pruessner, Jens; Newhouse, Paul

    2015-09-01

    Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle-related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The clinical analysis of expression levels of IL-6, BNP and CRP in patients with brain injury

    Institute of Scientific and Technical Information of China (English)

    Jun-Feng Zhang

    2015-01-01

    Objective: To investigate the clinical analysis of expression levels of brain natriuretic peptide (BNP), interleukin -6 (IL-6), C-reactive protein (CRP) in patients with traumatic brain injury and its clinical significance. Methods: The levels of IL-6, BNP, CRP of 80 cases of traumatic brain injury and 80 cases of healthy people group were determined with radioimmunoassay and immunoassays. Results: The levels of IL-6 and CRP of patients with traumatic brain injury were higher than healthy people group (P<0.05), while the levels of BNP of patients with traumatic brain injury were lower than healthy people group (P<0.05). The levels of CRP and IL-6 of patients with severe were higher than light and moderate traumatic brain injury patients (P<0.05) .Compared with the time of admission, the serum BNP, IL-6 and -CRP levels of the patient admitted to hospital within 24 h reached a peak and gradually decreased in 3d after admission, compared with the previous admission, the difference was statistically significant (P<0.05). The levels of BNP of the severe were lower than light and moderate traumatic brain injury patients (P<0.05). Conclusions: The measurement of serum BNP, IL-6 and CRP levels will help to evaluate the extent of disease in elderly patients with traumatic brain injury and prognosis.

  8. [Effect of positive pressure respiration on diurnal catecholamine excretion by patients with obstructive sleep apnea].

    Science.gov (United States)

    Cieślicki, J; Wocial, B; Koziej, M; Pałasiewicz, G; Zieliński, J

    1996-02-01

    The aim of the study was to investigate effects of CPAP treatment on diurnal catecholamine excretion in urine in patients with obstructive sleep apnea (OSA). 12 males with severe OSA (mean AHI = 63) were measured in 3 separate 8 hour samples by fluorimetric method. NA levels were higher in OSA patients in all urine samples than in obese, mildly hypertensive males (control group = C). In C group patients NA levels were significantly lower at night than during the day contrary to OSA patients in whom NA levels dropped insignificantly during sleep. In OSA patients NA levels during sleep correlated with severity of apneas (r = 0.42) and night hypoxaemia (r = -0.46). CPAP treatment resulted in significant fall in NA levels during sleep (p sleep in OSA patients may be related to sleep fragmentation and hypoxia. CPAP treatment restores normal circadian rhythm of NA excretion.

  9. Training status (endurance or sprint) and catecholamine response to the Wingate-test in women.

    Science.gov (United States)

    Jacob, C; Zouhal, H; Vincent, S; Gratas-Delamarche, A; Berthon, P M; Bentué-Ferrer, D; Delamarche, P

    2002-07-01

    The aim of this study was to verify if, as for men, training status induces different catecholamine responses to exercise. To do this, we investigated the effect of training status (sprint or endurance) on plasma catecholamine response to a supramaximal exercise in women. Nineteen subjects took part in our study: six untrained subjects (UT), seven endurance trained subjects (ET) and six sprint trained ones (ST). The trained subjects (ET and ST) were all competing at a high national level. The maximal power (W max ) and the mean power (W) were determined from the Wingate-test. Blood lactate, adrenaline (A) and noradrenaline (NA) were analysed at rest (La 0, A 0 and NA 0 ), immediately at the end of the exercise (A max and NA max ) and after 5 min recovery (La max [3 min in arterialized blood], A 5 and NA 5 ). The disappearance of A and NA was judged by the ratio (A max -A 5 )/A max and (NA max -NA 5 )/NA 5. The ratio A max /NA max was considered as an index of the adrenal medulla responsiveness to the sympathetic nervous activity. As expected, during the Wingate-test ST exhibited significantly higher performances compared to UT and ET. But in contrast to the men's data no difference was observed between the three groups both for La max (13.1 +/- 0.8 mmol x L (-1); 14.8 +/- 1.0 mmol x L (-1) and 11.2 +/- 0.5 mmol x L (-1) respectively for ET, ST and UT), NA max (22.1 +/- 1.2 nmol x L (-1); 13.1 +/- 2.4 nmol x L (-1) and 20.2 +/- 7 nmol x L (-1)respectively for ET, ST and UT) and A max (4.1 +/- 0.8 nmol x L (-1); 2.6 +/- 0.6 nmol x L (-1); 13.1 +/- 0.6 nmol x L (-1) respectively for ET, ST and UT). Consequently the ratio A max /NA max was similar in UT, ET and ST (respectively 0.2 +/- 0.03; 0.2 +/- 0.04; 0.17 +/- 0.04), These results indicated, in contrast to the men's data, that the catecholamine response to the Wingate-test did not differ between female subjects of different status of training. In conclusion this study did not find any significant effect of training

  10. A survey of human brain transcriptome diversity at the single cell level.

    Science.gov (United States)

    Darmanis, Spyros; Sloan, Steven A; Zhang, Ye; Enge, Martin; Caneda, Christine; Shuer, Lawrence M; Hayden Gephart, Melanie G; Barres, Ben A; Quake, Stephen R

    2015-06-09

    The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.

  11. Prenatal malnutrition and lead intake produce increased brain lipid peroxidation levels in newborn rats.

    Science.gov (United States)

    Maldonado-Cedillo, Brenda Gabriela; Díaz-Ruiz, Araceli; Montes, Sergio; Galván-Arzate, Sonia; Ríos, Camilo; Beltrán-Campos, Vicente; Alcaraz-Zubeldia, Mireya; Díaz-Cintra, Sofia

    2016-09-01

    Prenatal malnutrition (M) and lead intoxication (Pb) have adverse effects on neuronal development; one of the cellular mechanisms involved is a disruption of the pro- and anti-oxidant balance. In the developing brain, the vulnerability of neuronal membrane phospholipids is variable across the different brain areas. This study assesses the susceptibility of different brain regions to damage by quitar tissue oxidative stress and lead quitar concentrations to determine whether the combined effect of prenatal malnutrition (M) and lead (Pb) intoxication is worse than the effect of either of them individually. M was induced with an isocaloric and hypoproteinic (6% casein) diet 4 weeks before pregnancy. Intoxication was produced with lead acetate in drinking water, from the first gestational day. Both the M and Pb models were continued until the day of birth. Four brain regions (hippocampus, cortex, striatum, and cerebellum) were dissected out to analyze the lipid peroxidation (LP) levels in four groups: normally nourished (C); normally nourished but intoxicated with lead (CPb); malnourished (M); and M intoxicated with lead (MPb). Dam body and brain weights were significantly reduced in the fourth gestational week in the MPb group. Their pups had significantly lower body weights than those in the C and CPb groups. The PbM group exhibited significant increases of lead concentration and LP in all areas evaluated. A potentiation effect of Pb and M on LP was found in the cerebellum. This study provides information on how environmental conditions (intoxication and malnutrition) during the intrauterine period could differentially affect the development of neuronal plasticity and, in consequence, alter adult brain functions such as learning and memory.

  12. Association between serum tissue inhibitor of matrix metalloproteinase-1 levels and mortality in patients with severe brain trauma injury

    National Research Council Canada - National Science Library

    Lorente, Leonardo; Martín, María M; López, Patricia; Ramos, Luis; Blanquer, José; Cáceres, Juan J; Solé-Violán, Jordi; Solera, Jorge; Cabrera, Judith; Argueso, Mónica; Ortiz, Raquel; Mora, María L; Lubillo, Santiago; Jiménez, Alejandro; Borreguero-León, Juan M; González, Agustín; Orbe, Josune; Rodríguez, José A; Páramo, José A

    2014-01-01

    ...) play a role in neuroinflammation after brain trauma injury (TBI). Previous studies with small sample size have reported higher circulating MMP-2 and MMP-9 levels in patients with TBI, but no association between those levels and mortality...

  13. Critical levels of brain atrophy associated with homocysteine and cognitive decline.

    Science.gov (United States)

    de Jager, Celeste A

    2014-09-01

    Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency.

  14. Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

    OpenAIRE

    Mastroeni, Diego; Chouliaras, Leonidas; Daniel L. Van den Hove; Nolz, Jennifer; Rutten, Bart P. F.; Delvaux, Elaine; Coleman, Paul D.

    2016-01-01

    The subventricular zone (SVZ) is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the “normal” distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase...

  15. The MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels

    OpenAIRE

    Oien, Derek B.; Osterhaus, Greg L.; Latif, Shaheen A.; Pinkston, Jonathan W.; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C.; Moskovitz, Jackob

    2008-01-01

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA−/−) mouse. Here we show that MsrA−/− mice have compromised complex task lear...

  16. Effect of angiotensin II, catecholamines and glucocorticoid on corticotropin releasing factor (CRF-induced ACTH release in pituitary cell cultures.

    Directory of Open Access Journals (Sweden)

    Murakami,Kazuharu

    1984-08-01

    Full Text Available The effects of angiotensin II, catecholamines and glucocorticoid on CRF-induced ACTH release were examined using rat anterior pituitary cells in monolayer culture. Synthetic ovine CRF induced a significant ACTH release in this system. Angiotensin II produced an additive effect on CRF-induced ACTH release. The ACTH releasing activity of CRF was potentiated by epinephrine and norepinephrine. Dopamine itself at 0.03-30 ng/ml did not show any significant effect on ACTH release, but it inhibited CRF-induced ACTH release. Corticosterone at 10(-7 and 10(-6M inhibited CRF-induced ACTH release. These results indicate that angiotensin II, catecholamines and glucocorticoid modulate ACTH release at the pituitary level.

  17. Effects of Acute Lithium Treatment on Brain Levels of Inflammatory Mediators in Poststroke Rats

    Directory of Open Access Journals (Sweden)

    Matthew Boyko

    2015-01-01

    Full Text Available Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO. Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL- 6 and prostaglandin E2 levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-α levels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats.

  18. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  19. The catecholamine response to spaceflight: role of diet and gender

    Science.gov (United States)

    Stein, T. P.; Wade, C. E.

    2001-01-01

    Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. RESULTS: No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

  20. PGE2, PGF2 alpha and catecholamines in pheochromocytoma.

    Science.gov (United States)

    Ignatowska-Switalska, H; Wocial, B; Januszewicz, W; Filipecki, S

    1982-01-01

    In order to relate urinary prostaglandin excretion in pheochromocytoma (Ph) to the pattern of noradrenaline (NA), adrenaline (A) and dopamine (D), 14 patients with this disease were investigated during normal sodium intake. 20 healthy volunteers served as controls (C). Urinary PGs were determined by RIA; NA, A and D were measured fluorometrically. In patients with elevated excretion of NA + A (n=3), NA alone (n=6) and D (n=5), urinary PGE2 was significantly (p less than 0.01) diminished respectively 367,4 +/- 143,6; 445 +/- 104; 440,4 +/- 125,2 pmol/24h in comparison to C/1075 +/- 165,4 pmol/24 h. On the other hand urinary excretion of PGF2 alpha was distinctly increased in patients with elevated NA + A, normal NA + A and elevated D respectively 6375 +/- 1697, 1035 +/- 217,8, 5070 + 1225 pmol/24 h and decreased in patients with elevated A 989 +/- 217,5 pmol/24 h in comparison to C/1886 +/- 255,7 pmol/24 h. It is concluded, that in patients with Ph PGs excretion is related to the pattern of catecholamines excretion. Low PGE2 excretion in most patients with Ph suggests that the physiological interrelationship between catecholamines and PGs is disturbed in this disease. High PGF2 alpha excretion may reflect enhanced activity of 9-ketoreductase PGE2 probably caused by an excess of catecholamines.

  1. Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury

    Science.gov (United States)

    Wu, Xuehai; Zou, Qihong; Hu, Jin; Tang, Weijun; Mao, Ying; Gao, Liang; Zhu, Jianhong; Jin, Yi; Wu, Xin; Lu, Lu; Zhang, Yaojun; Zhang, Yao; Dai, Zhengjia; Gao, Jia-Hong; Weng, Xuchu; Northoff, Georg; Giacino, Joseph T.; He, Yong

    2015-01-01

    For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI. SIGNIFICANCE STATEMENT Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the

  2. Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes.

    Science.gov (United States)

    Ramos, Patrícia; Santos, Agostinho; Pinto, Edgar; Pinto, Nair Rosas; Mendes, Ricardo; Magalhães, Teresa; Almeida, Agostinho

    2016-12-01

    The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder. Potassium was found as the most abundant alkali metal, followed by Na, Rb, Cs and Li. Lithium, K and Cs distribution showed to be quite heterogeneous. On the contrary, Rb and Na appeared quite homogeneously distributed within the human brain tissue. The lowest levels of Na, K, Rb and Li were found in the brainstem (midbrain, medulla and pons) and cerebellum, while the lowest levels of Cs were found in the frontal cortex. The highest levels of K (mean±sd; range 15.5±2.5; 8.9-21.8mg/g) Rb (17.2±6.1; 3.9-32.4μg/g and Cs (83.4±48.6; 17.3-220.5ng/g) were found in putamen. The highest levels of Na and Li were found in the frontal cortex (11.6±2.4; 6.6-17.1mg/g) and caudate nucleus (7.6±4.6 2.2-21.3ng/g), respectively. Although K, Cs and Li levels appear to remain largely unchanged with age, some age-related changes were observed for Na and Rb levels in particular brain regions (namely in the hippocampus). Copyright © 2016 Elsevier GmbH. All

  3. Structural and diffusional brain abnormality related to relatively low level alcohol consumption.

    Science.gov (United States)

    Sasaki, Hiroki; Abe, Osamu; Yamasue, Hidenori; Fukuda, Rin; Yamada, Haruyasu; Takei, Kunio; Suga, Motomu; Takao, Hidemasa; Kasai, Kiyoto; Aoki, Shigeki; Ohtomo, Kuni

    2009-06-01

    Chronic excessive alcohol intake results in alcohol-related brain damage. Many previous reports have documented alcohol-related global or local brain shrinkage or diffusional abnormalities among alcoholics and heavy to moderate drinkers; however, the influence of relatively low levels of alcohol consumption on brain structural or diffusional abnormality is unclear. We investigated structural or diffusional abnormalities related to lifetime alcohol consumption (LAC) using voxel-based morphometry (VBM) among Japanese non-alcohol-dependent individuals (114 males, 97 females). High-resolution three-dimensional magnetic resonance images and diffusion tensor imaging were acquired in all subjects. The collected images were normalized, segmented, and smoothed using SPM 5. Gray matter volume (GMV) and white matter volume (WMV) were normalized for each total intracranial volume (TIV), and partial correlation coefficients were estimated between normalized GMV or WMV and lifetime alcohol consumption (LAC) adjusted for age. To investigate regional GMV or WMV abnormalities related to LAC, multiple regression analyses were performed among regional GMV or WMV and LAC, age, and TIV. To investigate subtle regional abnormalities, multiple regression analyses were performed among fractional anisotropy (FA) or mean diffusivity (MD), and LAC and age. No LAC-related global or regional GMV or WMV abnormality or LAC-related regional FA abnormality was found among male or female subjects. Significant LAC-related MD increase was found in the right amygdala among female subjects only. The current results suggest female brain vulnerability to alcohol, and a relation between subtle abnormality in the right amygdala and alcohol misuse.

  4. Decreased brain-derived neurotrophic factor plasma levels in psoriasis patients

    Directory of Open Access Journals (Sweden)

    A.R. Brunoni

    2015-08-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is associated with neuroplasticity and synaptic strength, and is decreased in conditions associated with chronic stress. Nevertheless, BDNF has not yet been investigated in psoriasis, a chronic inflammatory systemic disease that is exacerbated by stress. Therefore, our aim was to determine BDNF plasma levels in psoriasis patients and healthy controls. Adult patients (n=94 presenting with psoriasis for at least 1 year were enrolled, and age- and gender-matched with healthy controls (n=307 from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil. Participants had neither a previous history of coronary artery disease nor current episode of major depression. BDNF plasma levels were determined using the Promega ELISA kit. A general linear model was used to compare BDNF levels in psoriasis patients and controls, with age, gender, systolic blood pressure, serum fasting glucose, blood lipid levels, triglycerides, smoking status, and body mass index examined. After adjusting for clinical and demographic variables, significantly decreased BNDF plasma levels were observed in psoriasis patients (P=0.01 (estimated marginal means of 3922 pg/mL; 95%CI=2660-5135 compared with controls (5788 pg/mL; 95%CI=5185-6442. Similar BDNF levels were found in both mild and severe cases of psoriasis. Our finding, that BDNF is decreased in psoriasis, supports the concept of a brain-skin connection in psoriasis. Further studies should determine if BDNF is increased after specific psoriasis treatments, and associated with different disease stages.

  5. Changes in neurotransmitter receptor expression levels in rat brain after 4-week exposure to 1-bromopropane.

    Science.gov (United States)

    Mohideen, Sahabudeen Sheik; Ichihara, Sahoko; Banu, Shameema; Liu, Fang; Kitoh, Junzoh; Ichihara, Gaku

    2009-11-01

    1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, exhibits neurotoxicity and reproductive toxicity in animals and humans. The present study investigated the effects of exposure to 1-BP on expression of neurotransmitter receptor genes in the rat brain to explore possible biomarkers for central neurotoxicity and find brain regions sensitive for microarray analysis. Thirty-six F344 rats were divided at random into four equal groups of nine and exposed to 1-BP at 0, 400, 800 and 1000 ppm for 8 h/day; 7 days/week for 4 weeks. Total RNA from different brain regions was extracted and real-time PCR was conducted to quantify the mRNA levels of serotonin, dopamine and GABA receptors. Western blot analysis for specific regions of interest was also carried out to determine the protein levels. The mRNAs of 5HTr2a, D2R and GABAa1 were down regulated in a 1-BP dose-dependent manner in the hippocampus. The mRNA levels of 5HTr1a, 5HTr2a, D1R and GABAa1 were significantly decreased in the cortex of rats exposed to 800 ppm, but not to 1000 ppm. The mRNAs of 5HTr1a and 5HTr3a in the pons-medulla were decreased in rats exposed to 400 ppm or higher concentrations. The mRNA expression of D2R in the hippocampus and 5HTr1a and 5HTr3a in the pons-medulla oblongata were the most sensitive indicators of 1-BP neurotoxicity. The results suggest that mRNA expression analysis is useful in identifying brain regions susceptible to 1-BP, as well as providing potential biomarkers for central nervous system toxicity.

  6. Level set segmentation of brain magnetic resonance images based on local Gaussian distribution fitting energy.

    Science.gov (United States)

    Wang, Li; Chen, Yunjie; Pan, Xiaohua; Hong, Xunning; Xia, Deshen

    2010-05-15

    This paper presents a variational level set approach in a multi-phase formulation to segmentation of brain magnetic resonance (MR) images with intensity inhomogeneity. In our model, the local image intensities are characterized by Gaussian distributions with different means and variances. We define a local Gaussian distribution fitting energy with level set functions and local means and variances as variables. The means and variances of local intensities are considered as spatially varying functions. Therefore, our method is able to deal with intensity inhomogeneity without inhomogeneity correction. Our method has been applied to 3T and 7T MR images with promising results.

  7. Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function.

    Science.gov (United States)

    Teixeira, Antonio Lucio; Barbosa, Izabela Guimarães; Diniz, Breno Satler; Kummer, Arthur

    2010-12-01

    Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS, where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have consistently reported altered levels of BDNF in the circulation (i.e., serum or plasma) of patients with major depression, bipolar disorder, Alzheimer's disease, Huntington's disease and Parkinson's disease. Correlations between serum BDNF levels and affective, cognitive and motor symptoms have also been described. BDNF appears to be an unspecific biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.

  8. Evaluation of zinc effect on cadmium action in lipid peroxidation and metallothionein levels in the brain

    Directory of Open Access Journals (Sweden)

    Marcos M. Braga

    2015-01-01

    Full Text Available Cadmium (Cd is a known hepato- and nephrotoxic pollutant and zinc (Zn metalloproteins are important targets of Cd. Hence, the administration of Zn may mitigate Cd toxic effects. However, the interaction of Cd and Zn has been little investigated in the brain. Previously, we reported a protective effect of Zn on mortality caused by Cd in rats. Here, we tested whether the protective effect of Zn could be related to changes in brain Zn-proteins, metallothionein (MT and δ-aminolevulinate dehydratse (δ-ALA-D. Male adult rats were daily administered for 10 days with Zn (2 mg kg−1, Cd (0.25 and 1 mg kg−1 and 0.25 mg kg−1 of Cd plus Zn and 1 mg kg−1 of Cd plus Zn. The body weight loss, food intake deprivation, and mortality occurred in 1 mg kg−1 of Cd, but Zn co-administration did mitigate these effects. The brain Zn content was not modified by treatment with Cd, whereas cerebral Cd levels increased in animals exposed to Cd. The administration of 0.25 mg kg−1 of Cd (with or without Zn induced lipid peroxidation and decreased MT concentration, but 2 mg kg−1 of Zn and 1 mg kg−1 of Cd did not change these parameters. Brain δ-ALA-D was not modified by Cd and/or Zn treatments. Since the co-administration of Zn did not attenuate the changes induced by Cd in the brain, our results suggest that the protective effect of Zn on impairments caused by Cd in animal status is weakly related to a cerebral interaction of these metals.

  9. Serial Serum Leukocyte Apoptosis Levels as Predictors of Outcome in Acute Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Hung-Chen Wang

    2014-01-01

    Full Text Available Background. Apoptosis associates with secondary brain injury after traumatic brain injury (TBI. This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome. Methods. Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects. Results. The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (P=0.009, motor deficits (P≤0.001, GCS (P≤0.001, ISS (P=0.001, WBC count (P=0.015, late apoptosis in lymphocytes and monocytes on Day 1 (P=0.004 and P=0.022, resp., subdural hemorrhage on initial brain CT (P=0.002, neurosurgical intervention (P≤0.001, and acute posttraumatic seizure (P=0.046 were significant risk factors of outcome. Only motor deficits (P=0.033 and late apoptosis in monocytes on Day 1 (P=0.037 were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients. Conclusion. There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury.

  10. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    Science.gov (United States)

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  11. How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1.

    Science.gov (United States)

    Serra, Laura; Petrucci, Antonio; Spanò, Barbara; Torso, Mario; Olivito, Giusy; Lispi, Ludovico; Costanzi-Porrini, Sandro; Giulietti, Giovanni; Koch, Giacomo; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2015-01-01

    Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular impairment and brain dysfunctions. Although brain damage has previously been demonstrated in DM1, its associations with the genetics and clinical/neuropsychological features of the disease are controversial. This study assessed the differential role of gray matter (GM) and white matter (WM) damage in determining higher-level dysfunctions in DM1. Ten patients with genetically confirmed DM1 and 16 healthy How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1 matched controls entered the study. The patients underwent a neuropsychological assessment and quantification of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with studies including T1-weighted volumes and diffusion-weighted images. Voxel-based morphometry and tractbased spatial statistics were used for unbiased quantification of regional GM atrophy and WM integrity. The DM1 patients showed widespread involvement of both tissues. The extent of the damage correlated with CTG triplet expansion and cognition. This study supports the idea that genetic abnormalities in DM1mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1.

  12. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism.

    Science.gov (United States)

    Shin, Andrew C; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A; Zielinski, Elizabeth; Zhou, Jian-Ying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J; Lapworth, Amanda L; Ilkayeva, Olga; Knippschild, Uwe; Wolf, Anna M; Scheja, Ludger; Grove, Kevin L; Smith, Richard D; Qian, Wei-Jun; Lynch, Christopher J; Newgard, Christopher B; Buettner, Christoph

    2014-11-04

    Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.

  13. IGF1R levels in the brain negatively correlate with longevity in 16 rodent species

    Science.gov (United States)

    Azpurua, Jorge; Yang, Jiang-Nan; Van Meter, Michael; Liu, Zhengshan; Kim, Julie; Lobo Ladd, Aliny AB; Coppi, Antonio Augusto; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The insulin/insulin-like growth factor signaling (IIS) pathway is a major conserved regulator of aging. Nematode, fruit fly and mouse mutants with reduced IIS signaling exhibit extended lifespan. These mutants are often dwarfs leading to the idea that small body mass correlates with longevity within species. However, when different species are compared, larger animals are typically longer-lived. Hence, the role of IIS in the evolution of life history traits remains unresolved. Here we used comparative approach to test whether IGF1R signaling changes in response to selection on lifespan or body mass and whether specific tissues are involved. The IGF1R levels in the heart, lungs, kidneys, and brains of sixteen rodent species with highly diverse lifespans and body masses were measured via immunoblot after epitope conservation analysis. We report that IGF1R levels display strong negative correlation with maximum lifespan only in brain tissue and no significant correlations with body mass for any organ. The brain-IGF1R and lifespan correlation holds when phylogenetic non-independence of data-points is taken into account. These results suggest that modulation of IGF1R signaling in nervous tissue, but not in the peripheral tissues, is an important factor in the evolution of longevity in mammals. PMID:23651613

  14. Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury.

    Science.gov (United States)

    Cao, Lijuan; Chen, Jieyu; Li, Mei; Qin, Yuan-Yuan; Sun, Meiling; Sheng, Rui; Han, Feng; Wang, Guanghui; Qin, Zheng-Hong

    2015-10-01

    In previous studies, we showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) protects neurons against ischemic brain injury. In the present study, we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury. We found that the TIGAR level was high in the embryonic stage, dropped at birth, partially recovered in the early postnatal period, and then continued to decline to a lower level in early adult and aged mice. The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8 and 12 weeks after birth. Four-week-old mice had smaller infarct volumes, lower neurological scores, and lower mortality rates after ischemia than 8- and 12-week-old mice. TIGAR expression also increased in response to oxygen glucose deprivation (OGD)/reoxygenation insult or H2O2 treatment in cultured primary neurons from different embryonic stages (E16 and E20). The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult. Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress. Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult. Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate (NADPH) significantly reduced ischemic injury. These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.

  15. Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels.

    Science.gov (United States)

    Parkhomenko, Yulia M; Kudryavtsev, Pavel A; Pylypchuk, Svetlana Yu; Chekhivska, Lilia I; Stepanenko, Svetlana P; Sergiichuk, Andrej A; Bunik, Victoria I

    2011-06-01

    Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability.

  16. Functional specificity for high-level linguistic processing in the human brain.

    Science.gov (United States)

    Fedorenko, Evelina; Behr, Michael K; Kanwisher, Nancy

    2011-09-27

    Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.

  17. Catecholamine release evoked by lithium from the perfused adrenal gland of the cat.

    OpenAIRE

    de Abajo, F. J.; Castro, M. A.; Garijo, B; Sánchez-García, P.

    1987-01-01

    The effect of Li on catecholamine release by cat isolated retrogradely perfused adrenal gland was investigated. Replacement of Na (119 mM) by Li in the Krebs solution evoked a progressive increase in the spontaneous release of catecholamines that reached a maximum within 45 min and was Ca-dependent. This response was specific for Li, since sucrose or choline used as osmotic substitutes for Na, failed to increase the spontaneous release of catecholamines by the adrenal gland. In glands perfuse...

  18. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine

    2013-01-01

    in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised......Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction...... that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher...

  19. Increased acetyl and total histone levels in post-mortem Alzheimer's disease brain.

    Science.gov (United States)

    Narayan, Pritika J; Lill, Claire; Faull, Richard; Curtis, Maurice A; Dragunow, Mike

    2015-02-01

    Histone acetylation is an epigenetic modification that plays a critical role in chromatin remodelling and transcriptional regulation. There is increasing evidence that epigenetic modifications may become compromised in aging and increase susceptibility to the development of neurodegenerative disorders such as Alzheimer's disease. Immunohistochemical labelling of free-floating sections from the inferior temporal gyrus (Alzheimer's disease, n=14; control, n=17) and paraffin-embedded tissue microarrays containing tissue from the middle temporal gyrus (Alzheimer's disease, n=29; control, n=28) demonstrated that acetyl histone H3 and acetyl histone H4 levels, as well as total histone H3 and total histone H4 protein levels, were significantly increased in post-mortem Alzheimer's disease brain tissue compared to age- and sex-matched neurologically normal control brain tissue. Changes in acetyl histone levels were proportional to changes in total histone levels. The increase in acetyl histone H3 and H4 was observed in Neuronal N immunopositive pyramidal neurons in Alzheimer's disease brain. Using immunolabelling, histone markers correlated significantly with the level of glial fibrillary acidic protein and HLA-DP, -DQ and -DR immunopositive cells and with the pathological hallmarks of Alzheimer's disease (hyperphosphorylated tau load and β-amyloid plaques). Given that histone acetylation changes were correlated with changes in total histone protein, it was important to evaluate if protein degradation pathways may be compromised in Alzheimer's disease. Consequently, significant positive correlations were also found between ubiquitin load and histone modifications. The relationship between histone acetylation and ubiquitin levels was further investigated in an in vitro model of SK-N-SH cells treated with the proteasome inhibitor Mg132 and the histone deacetylase inhibitor valproic acid. In this model, compromised protein degradation caused by Mg132 lead to elevated histone

  20. Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Keller, U.; Lustenberger, M.; Mueller-Brand, J.G.; Gerber, P.P.; Stauffacher, W.

    1989-05-01

    Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and thus releasing free fatty acids, but also by increasing intrahepatic ketogenesis. Thyroid hormone availability was associated with lipolysis and ketogenesis. Ketone body concentrations after an overnight fast were only modestly elevated in hyperthyroidism resulting from increased peripheral ketone body clearance. There was a significant correlation between serum triiodothyronine levels and the ketone body metabolic clearance rate. Thus, ketone body homeostasis in human subjects resulted from the interaction of hormones such as insulin, catecholamines, and thyroid hormones regulating lipolysis, intrahepatic ketogenesis, and peripheral ketone body utilization. 58 references.

  1. Influence of high- and low-carbohydrate diet following glycogen-depleting exercise on heart rate variability and plasma catecholamines.

    Science.gov (United States)

    Lima-Silva, Adriano Eduardo; Bertuzzi, Rômulo; Dalquano, Elen; Nogueira, Marie; Casarini, Dulce; Kiss, Maria Augusta; Ugrinowitsch, Carlos; Pires, Flávio de Oliveira

    2010-08-01

    The purpose of this study was to investigate the effects of a short-term low- or high-carbohydrate (CHO) diet consumed after exercise on sympathetic nervous system activity. Twelve healthy males underwent a progressive incremental test; a control measurement of plasma catecholamines and heart rate variability (HRV); an exercise protocol to reduce endogenous CHO stores; a low- or high-CHO diet (counterbalanced order) consumed for 2 days, beginning immediately after the exercise protocol; and a second resting plasma catecholamine and HRV measurement. The exercise and diet protocols and the second round of measurements were performed again after a 1-week washout period. The mean (+/-SD) values of the standard deviation of R-R intervals were similar between conditions (control, 899.0+/-146.1 ms; low-CHO diet, 876.8+/-115.8 ms; and high-CHO diet, 878.7+/-127.7 ms). The absolute high- and low-frequency (HF and LF, respectively) densities of the HRV power spectrum were also not different between conditions. However, normalized HF and LF (i.e., relative to the total power spectrum) were lower and higher, respectively, in the low-CHO diet than in the control diet (mean+/-SD, 17+/-9 normalized units (NU) and 83+/-9 NU vs. 27+/-11 NU and 73+/-17 NU, respectively; pheart rate was modified after a short-term low-CHO diet, but plasma catecholamine levels were not altered.

  2. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    Science.gov (United States)

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

  3. Screening for impact of popular herbs improving mental abilities on the transcriptional level of brain transporters

    Directory of Open Access Journals (Sweden)

    Mrozikiewicz Przemyslaw M.

    2014-06-01

    Full Text Available There are a number of compounds that can modify the activity of ABC (ATP-binding cassette and SLC (solute carrier transporters in the blood-brain barrier (BBB. The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1. Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital and natural (codeine, cyclosporine A, quercetin substances showed a selective inhibitory effect. Further, the extract from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas the extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes, except for mrp2. Extract from the aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB

  4. Effects of catecholamine-β-adrenoceptor-cAMP system on severe patients with heart failure

    Institute of Scientific and Technical Information of China (English)

    彭应心; 单江; 齐晓勇; 薛浩; 容春莉; 姚冬梅; 郭志琴; 郑师凌

    2003-01-01

    Objective To investigate the association between catecholamine-β-adrenoceptor (β-AR)-adenosine 3', 5'-monophosphate (cAMP) system and long-term prognosis in patients with chronic heart failure (CHF).Methods The study population comprised 73 patients with CHF (EF: 23%±10%) with a mean follow-up of 3.8±1.9 years. Plasma levels of norepinephrine (NE) were measured using high performance lipid chromatography, β-adrenergic receptor density (Bmax) and the content of cAMP in peripheral lymphocytes were calculated using 3H-dihydroalpneolo as ligand and competitive immunoassay, respectively. Deaths due to cardiovascular events within the follow-up period were registered.Results The total mortality was 64.7%, 57.4% of which was for cardiogenic (worsening heart failure: 32.4%; sudden death: 25.0%). In the cardiogenic death group, plasma levels of NE and epinephrine (E) (3.74 nmol/L±0.09 nmol/L and 3.17 nmol/L±1.0nmol/L) and the contents of peripheral lymphocyte cAMP (3.64 pmol/mg protein±1.4 pmol/mg protein) were significantly increased as compared with the survival group (2.68 nmol/L±0.07 nmol/L, 2.41 nmol/L±0.24 nmol/L and 2.73 pmol/mg protein±0.9 pmol/mg protein, respectively, all P4.5 nmol/L, respectively. In the worsening heart failure group, the content of peripheral lymphocyte cAMP (4.46 pmol/mg protein±0.18 pmol/mg protein) was significantly increased compared with the sudden death group (2.39 pmol/mg protein±0.9 pmol/mg protein, P4.5nmol/L, respectively. Bmax in peripheral lymphocyte was not significantly different (P>0.05) among the sudden death, worsening heart failure, and survival groups in CHF patients.Conclusions Plasma levels of catecholamine increase significantly, and Bmax and the contents of cAMP in peripheral lymphocytes decrease significantly in patients with CHF. High plasma catecholamine levels may be associated with sudden death, and high intralymphocyte cAMP content may be associated with worsening heart failure in CHF patients.

  5. Prenatal exposure to zinc oxide particles alters monoaminergic neurotransmitter levels in the brain of mouse offspring.

    Science.gov (United States)

    Okada, Yuka; Tachibana, Ken; Yanagita, Shinya; Takeda, Ken

    2013-01-01

    Zinc oxide (ZnO) nano-sized particles (NPs) are beneficial materials used for sunscreens and cosmetics. Although ZnO NPs are widely used for cosmetics, the health effects of exposure during pregnancy on offspring are largely unknown. Here we investigated the effects of prenatal exposure to ZnO NPs on the monoaminergic system of the mouse brain. Subcutaneous administration of ZnO NPs to the pregnant ICR mice (total 500 μg/mouse) were carried out and then measured the levels of dopamine (DA), serotonin (5-HT), and noradrenalin, and their metabolites in 9 regions of the brain of offspring (6-week-old) using high performance liquid chromatography (HPLC). HPLC analysis demonstrated that DA levels were increased in hippocampus in the ZnO NP exposure group. In the levels of DA metabolites, homovanillic acid was increased in the prefrontal cortex and hippocampus, and 3, 4-dihydroxyphenylacetic acid was increased in the prefrontal cortex by prenatal ZnO NP exposure. Furthermore, DA turnover levels were increased in the prefrontal cortex, neostriatum, nucleus accumbens, and amygdala in the ZnO NP exposure group. We also found changes of the levels of serotonin in the hypothalamus, and of the levels of 5-HIAA (5-HT metabolite) in the prefrontal cortex and hippocampus in the ZnO NP-exposed group. The levels of 5-HT turnover were increased in each of the regions except for the cerebellum by prenatal ZnO NP exposure. The present study indicated that prenatal exposure to ZnO NPs might disrupt the monoaminergic system, and suggested the possibility of detrimental effects on the mental health of offspring.

  6. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bruno Silva

    2015-08-01

    Full Text Available The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO, a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

  7. Inhibition of fatty acid binding proteins elevates brain anandamide levels and produces analgesia.

    Directory of Open Access Journals (Sweden)

    Martin Kaczocha

    Full Text Available The endocannabinoid anandamide (AEA is an antinociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by fatty acid amide hydrolase (FAAH. Fatty acid binding proteins (FABPs are intracellular carriers that deliver AEA and related N-acylethanolamines (NAEs to FAAH for hydrolysis. The mammalian brain expresses three FABP subtypes: FABP3, FABP5, and FABP7. Recent work from our group has revealed that pharmacological inhibition of FABPs reduces inflammatory pain in mice. The goal of the current work was to explore the effects of FABP inhibition upon nociception in diverse models of pain. We developed inhibitors with differential affinities for FABPs to elucidate the subtype(s that contributes to the antinociceptive effects of FABP inhibitors. Inhibition of FABPs reduced nociception associated with inflammatory, visceral, and neuropathic pain. The antinociceptive effects of FABP inhibitors mirrored their affinities for FABP5, while binding to FABP3 and FABP7 was not a predictor of in vivo efficacy. The antinociceptive effects of FABP inhibitors were mediated by cannabinoid receptor 1 (CB1 and peroxisome proliferator-activated receptor alpha (PPARα and FABP inhibition elevated brain levels of AEA, providing the first direct evidence that FABPs regulate brain endocannabinoid tone. These results highlight FABPs as novel targets for the development of analgesic and anti-inflammatory therapeutics.

  8. Cerebral Taurine Levels are Associated with Brain Edema and Delayed Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage.

    Science.gov (United States)

    Kofler, Mario; Schiefecker, Alois; Ferger, Boris; Beer, Ronny; Sohm, Florian; Broessner, Gregor; Hackl, Werner; Rhomberg, Paul; Lackner, Peter; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

    2015-12-01

    Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting. We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects. CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p taurine levels compared to those without (Wald = 7.3, df = 1, p taurine supplementation and brain extracellular taurine (p = 0.6). Moreover, a significant correlation with brain extracellular glutamate (r = 0.82, p taurine levels were found in patients with brain edema or DCI after aneurysmal subarachnoid hemorrhage. Its value as a potential biomarker deserves further investigation.

  9. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel

    2014-01-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3...... were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder...

  10. Changes in Therapeutic Intensity Level Following Airway Pressure Release Ventilation in Severe Traumatic Brain Injury.

    Science.gov (United States)

    Fletcher, Jeffrey J; Wilson, Thomas J; Rajajee, Venkatakrishna; Davidson, Scott B; Walsh, Jon C

    2016-09-20

    Airway pressure release ventilation (APRV) utilizes high levels of airway pressure coupled with brief expiratory release to facilitate open lung ventilation. The aim of our study was to evaluate the effects of APRV-induced elevated airway pressure mean in patients with severe traumatic brain injury. This was a retrospective cohort study at a 424-bed Level I trauma center. Linear mixed effects models were developed to assess the difference in therapeutic intensity level (TIL), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) over time following the application of APRV. The study included 21 epochs of APRV in 21 patients. In the 6-hour epoch following the application of APRV, the TIL was significantly increased (P = .002) and the ICP significantly decreased (P = .041) compared to that before 6 hours. There was no significant change in CPP (P = .42) over time. The baseline static compliance and time interaction was not significant for TIL (χ(2) = 0.2 [df 1], P = .655), CPP (χ(2) = 0 [df 1], P = 1), or ICP (χ(2) = 0.1 [df 1], P = .752). Application of APRV in patients with severe traumatic brain injury was associated with significantly, but not clinically meaningful, increased TIL and decreased ICP. No significant change in CPP was observed. No difference was observed based on the baseline pulmonary static compliance. © The Author(s) 2016.

  11. Low-light-level therapy as a treatment for minimal hepatic encephalopathy: behavioural and brain assessment.

    Science.gov (United States)

    Arias, Natalia; Méndez, Marta; Arias, Jorge L

    2016-11-01

    Minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments involved in MHE. We studied one of its precipitating factors, portal hypertension. The purpose was to evaluate an enhancement in neuronal metabolism through low-light-level therapy (LLLT) and whether this therapy has effects on behavioural task acquisition. Rats were trained to perform a stimulus-response task using the Morris water maze. Three groups of animals were used: a SHAM (sham-operated) group (n = 7), a portal hypertension (PH) group (n = 7) and a PH + LLLT group (n = 7). The triple portal vein ligation method was used to create an animal model of the early developmental phase of HE, and then the animals were exposed to 670 + 10 nm LED light at a dose of 9 J/cm(2) once a day for 7 days. The metabolic activity of the brains was studied with cytochrome c oxidase histochemistry. There were differences in behavioural performance, with an improvement in the PH + LLLT group. Energetic brain metabolism revealed significant differences between the groups in all the brain structures analysed, except the anterodorsal thalamus. At the same time, in different brain networks, the PH group showed a more complicated relationship among the structures, while the SHAM and PH + LLLT groups had similar patterns. In this study, we provide the first preliminary insights into the validity of LLLT as a possible intervention to improve memory under minimal hepatic encephalopathy conditions.

  12. Prostaglandins, renin, aldosterone, and catecholamines in preeclampsia.

    Science.gov (United States)

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A B; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

  13. Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

    Directory of Open Access Journals (Sweden)

    Diego Mastroeni

    2016-06-01

    Full Text Available The subventricular zone (SVZ is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the “normal” distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase in hydroxymethylation directly correlates to an increase in cellular proliferation in Alzheimer's disease precursor cells, which implicates the hydroxymethylation tag to a higher degree of cellular proliferation.

  14. Brain levels of N-acylethanolamine phospholipids in mice during pentylenetetrazol-induced seizure

    DEFF Research Database (Denmark)

    Moesgaard, B.; Hansen, H.H.; Petersen, G.

    2003-01-01

    The N-acylethanolamine phospholipids (NAPE) are precursors for N-acylethanolamines (NAE), including anandamide (20:4-NAE), which is a ligand for the cannabinoid receptors. Previously, NAPE were believed to be found only in injured tissue, e.g., after neurodegenerative insults. Neuronal injury may...... and of N-acyltransferase in brain membrane preparations from adult and 3-d-old mice revealed an enzyme pattern in the adult mice that was favorable for NAE accumulation as opposed to NAPE accumulation. Thus, there was no difference in NAPE levels; at present, however, this does not exclude that NAE may...

  15. Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    i Dali, C; Hanson, L G; Barton, N W

    2010-01-01

    and is known as a marker for neuronal and axonal loss. NAA and other metabolite levels measured by proton magnetic resonance spectroscopy (MRS) correlate with performance of the brain in normal children. There is a need for sensitive measures of disease progression in patients with MLD to enable development......Late infantile metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder that causes severe demyelination of the nervous system. The neuronal metabolite N-acetylaspartate (NAA) serves as a source of acetyl groups for myelin lipid synthesis in oligodendrocytes...

  16. Posterior cingulate cross-hemispheric functional connectivity predicts the level of consciousness in traumatic brain injury.

    Science.gov (United States)

    Zhang, Haosu; Dai, Rui; Qin, Pengmin; Tang, Weijun; Hu, Jin; Weng, Xuchu; Wu, Xing; Mao, Ying; Wu, Xuehai; Northoff, Georg

    2017-03-24

    Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.

  17. Global Effects of Catecholamines on Actinobacillus pleuropneumoniae Gene Expression

    Science.gov (United States)

    Li, Lu; Xu, Zhuofei; Zhou, Yang; Sun, Lili; Liu, Ziduo; Chen, Huanchun; Zhou, Rui

    2012-01-01

    Bacteria can use mammalian hormones to modulate pathogenic processes that play essential roles in disease development. Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen causing great economic losses in the pig industry globally. Stress is known to contribute to the outcome of A. pleuropneumoniae infection. To test whether A. pleuropneumoniae could respond to stress hormone catecholamines, gene expression profiles after epinephrine (Epi) and norepinephrine (NE) treatment were compared with those from untreated bacteria. The microarray results showed that 158 and 105 genes were differentially expressed in the presence of Epi and NE, respectively. These genes were assigned to various functional categories including many virulence factors. Only 18 genes were regulated by both hormones. These genes included apxIA (the ApxI toxin structural gene), pgaB (involved in biofilm formation), APL_0443 (an autotransporter adhesin) and genes encoding potential hormone receptors such as tyrP2, the ygiY-ygiX (qseC-qseB) operon and narQ-narP (involved in nitrate metabolism). Further investigations demonstrated that cytotoxic activity was enhanced by Epi but repressed by NE in accordance with apxIA gene expression changes. Biofilm formation was not affected by either of the two hormones despite pgaB expression being affected. Adhesion to host cells was induced by NE but not by Epi, suggesting that the hormones affect other putative adhesins in addition to APL_0443. This study revealed that A. pleuropneumoniae gene expression, including those encoding virulence factors, was altered in response to both catecholamines. The differential regulation of A. pleuropneumoniae gene expression by the two hormones suggests that this pathogen may have multiple responsive systems for the two catecholamines. PMID:22347439

  18. Global effects of catecholamines on Actinobacillus pleuropneumoniae gene expression.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available Bacteria can use mammalian hormones to modulate pathogenic processes that play essential roles in disease development. Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen causing great economic losses in the pig industry globally. Stress is known to contribute to the outcome of A. pleuropneumoniae infection. To test whether A. pleuropneumoniae could respond to stress hormone catecholamines, gene expression profiles after epinephrine (Epi and norepinephrine (NE treatment were compared with those from untreated bacteria. The microarray results showed that 158 and 105 genes were differentially expressed in the presence of Epi and NE, respectively. These genes were assigned to various functional categories including many virulence factors. Only 18 genes were regulated by both hormones. These genes included apxIA (the ApxI toxin structural gene, pgaB (involved in biofilm formation, APL_0443 (an autotransporter adhesin and genes encoding potential hormone receptors such as tyrP2, the ygiY-ygiX (qseC-qseB operon and narQ-narP (involved in nitrate metabolism. Further investigations demonstrated that cytotoxic activity was enhanced by Epi but repressed by NE in accordance with apxIA gene expression changes. Biofilm formation was not affected by either of the two hormones despite pgaB expression being affected. Adhesion to host cells was induced by NE but not by Epi, suggesting that the hormones affect other putative adhesins in addition to APL_0443. This study revealed that A. pleuropneumoniae gene expression, including those encoding virulence factors, was altered in response to both catecholamines. The differential regulation of A. pleuropneumoniae gene expression by the two hormones suggests that this pathogen may have multiple responsive systems for the two catecholamines.

  19. Plasma brain natriuretic peptide levels are elevated in patients with cancer.

    Science.gov (United States)

    Bando, Sachiko; Soeki, Takeshi; Matsuura, Tomomi; Tobiume, Takeshi; Ise, Takayuki; Kusunose, Kenya; Yamaguchi, Koji; Yagi, Shusuke; Fukuda, Daiju; Iwase, Takashi; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Muguruma, Naoki; Takayama, Tetsuji; Kishimoto, Ichiro; Kangawa, Kenji; Sata, Masataka

    2017-01-01

    Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also been shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP levels in cancer patients, it remains unknown whether cancer-related inflammation affects the plasma BNP levels. We investigated the relationship between the BNP and human cancers. We retrospectively studied 2,923 patients in whom the plasma BNP levels and serum C-reactive protein (CRP) were measured and echocardiography was performed. Patients with clinically evident heart failure (NYHA II or higher), heart disease requiring medical treatment or surgery, renal dysfunction, and inflammatory disease were excluded. There were 234 patients in the final analysis. Blood sampling was performed before surgery and chemotherapy. In addition, we evaluated the relationship between the inflammation and plasma BNP levels in mouse models of colon cancer. Of the 234 patients, 80 were diagnosed with cancer. Both the plasma BNP and serum CRP levels were significantly higher in cancer patients than those without. There were no significant differences in the echocardiographic parameters. There was a significant positive correlation between the plasma BNP and serum CRP levels in cancer patients (r = 0.360, P<0.01) but not in those without. In cancer patients, only the CRP correlated with the BNP independent of the age, creatinine level, hypertension, and body mass index. In addition, in nude mice with subcutaneous colon cancer, the plasma BNP level was elevated compared with that in non-cancer mice, and there was a significant relationship between the plasma BNP and serum levels of the inflammatory markers. In cancer patients, as well as colon cancer model mice, the plasma BNP levels were elevated, possibly due to cancer-related inflammation. The effect of cancer on the BNP

  20. Influence of fatty acids on pressor responses to catecholamines.

    Science.gov (United States)

    Chopde, C T; Brahmankar, D M; Jadhav, S S; Hardas, A P; Dorle, A K

    1975-01-01

    Lauric, Myristic and Palmitic acids had no appreciable effect whereas Stearic, Oleic and Linoleic acids caused some reduction in dog blood pressure. Pressor responses to epinephrine and nor-epinephrine were potentiated whereas the depressor response to isoproterenol was reduced during the infusion of fatty acids in dogs. ACTH alone, which causes mobilization of free fatty acids had no appreciable effect on blood pressure responses to catecholamines, however, its administration followed by salicylate produced marked potentiation of the pressor responses to epinephrine and nor-epinephrine; the depressor response to isoproterenol was reduced.

  1. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    Directory of Open Access Journals (Sweden)

    Varsha Agarwal

    Full Text Available Cytochrome P450 (P450 is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  2. Stress-related changes in cerebral catecholamine and indoleamine metabolism: lack of effect of adrenalectomy and corticosterone.

    Science.gov (United States)

    Dunn, A J

    1988-08-01

    The concentrations of catecholamine and indoleamine metabolites were measured in intact and adrenalectomized mice to determine whether adrenal hormones mediate or modulate the stress-induced responses. Thirty minutes of footshock resulted in significant increases of the ratios of the dopamine (DA) catabolite, dihydroxyphenylacetic acid (DOPAC), to DA in prefrontal cortex, nucleus accumbens, striatum, hypothalamus, and brainstem, and of homovanillic (HVA)/DA ratios in nucleus accumbens, striatum, amygdala, and hypothalamus. Ratios of 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine (NE) were also increased in prefrontal cortex, nucleus accumbens, septum, amygdala, hypothalamus, hippocampus, and brainstem. The concentration of NE was decreased in amygdala. 5-Hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT, serotonin) ratios and free tryptophan were also increased in every brain region. Very similar data were obtained from mice restrained for 30 min. Adrenalectomy resulted in increased HVA/DA ratios in prefrontal cortex and striatum, and 5-HIAA/5-HT in septum. The stress-related changes were largely similar in adrenalectomized mice. Significant interactions between adrenalectomy and footshock treatment occurred in prefrontal cortical DOPAC/DA and hypothalamic NE which was depleted only in adrenalectomized mice, suggesting tendencies for these measures to be more responsive in adrenalectomized mice. Corticosterone administration (0.5-2.0 mg/kg s.c.) which resulted in plasma concentrations in the physiological range did not alter the concentrations of the cerebral metabolites measured in any region. We conclude that adrenal hormones do not mediate cerebral catecholamine or indoleamine metabolism in stress, although adrenalectomy may affect HVA and 5-HIAA metabolism, and there was a tendency for catecholamines to be more sensitive to stress in adrenalectomized animals.

  3. A new stress model, a scream sound, alters learning and monoamine levels in rat brain.

    Science.gov (United States)

    Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen

    2014-01-17

    Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time.

  4. Effect of Posttraumatic Serum Thyroid Hormone Levels on Severity and Mortality of Patients with Severe Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Forough Saki

    2012-02-01

    Full Text Available Traumatic brain injury (TBI is an important cause of death and disability in young adults ,and may lead to physical disabilities and long-term cognitive, behavioral psychological and social defects. There is a lack of definite result about the effect of thyroid hormones after traumatic brain injury in the severity and no data about their effect on mortality of the injury. The aim of this study is to evaluate the effect of thyroid hormones after traumatic brain injury in the severity and mortality and gain a clue in brain injury prognosis. In a longitudinal prospective study from February 2010 until February 2011, we checked serum levels of T3, T4, TSH and TBG of severely brain injured patients and compared the relationship of them with primary Glasgow Coma Scale (GCS score and mortality of patients. Statistical analysis used SPSS 11.5 software with using chi-square and Fisher exact test. Serum levels of T3 and T4 were decreased after brain trauma but not TSH and TBG. Mortality rates were higher in patients with lower T4 serum levels. The head injury was more severe in whom with low T3 and T4. Follow a severe brain injury a secondary hypothyroidism is happened due to pituitary dysfunction. Also, serum level of T3 and T4 on the first day admission affect on primary GCS score of patients which is an indicator of severity of brain injury. In addition, mortality rates of severely brain injured patients have a high correlation with the serum level of T4 in the first day admission.

  5. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression.

    Science.gov (United States)

    Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

    2015-03-04

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. In this cross-sectional study, a total of 123 inpatients with MDD (Diagnostic and Statistical Manual for Mental Disorders, 4th edition) at the Juntendo University Koshigaya Hospital were recruited. Serum levels of BDNF were measured. Personality traits were assessed using the 125-item short version of the Temperament and Character Inventory (TCI). Multiple regression analysis adjusted for age, sex, body mass index, dose of antidepressant, and depression severity showed that TCI Self-Directedness (SD) scores were negatively associated with serum BDNF levels (β = -0.23, p = 0.026). MDD patients who have low SD did not show the reduction in serum BDNF levels that is normally associated with depressive state. Our findings suggest that depression-related biological changes may not occur in these individuals.

  6. Effects of Glycemic Level on Outcome of Patients with Traumatic Brain Injury: A Retrospective Cohort Study

    Science.gov (United States)

    Alvis-Miranda, Hernando Raphael; Navas-Marrugo, Sandy Zuleica; Velasquez-Loperena, Robert Andrés; Adie-Villafañe, Richard José; Velasquez-Loperena, Duffay; Castellar-Leones, Sandra Milena; Alcala- Cerra, Gabriel; Pulido-Gutiérrez, Juan Camilo; Rodríguez-Conde, Javier Ricardo; Moreno-Moreno, María Fernanda; M. Rubiano, Andrés; Moscote-Salazar, Luis Rafael

    2014-01-01

    Objective: To determine the effects of glycemic level on outcome patients with traumatic brain injury. Methods:  From September 2010 to December 2012, all medical records of adult patients with TBI admitted to the Emergency Room of Laura Daniela Clinic in Valledupar City, Colombia, South America were enrolled. Both genders between 18 and 85 years who referred during the first 48 hours after trauma, and their glucose level was determined in the first 24 hours of admission were included. Adults older than 85 years, with absence of Glasgow Coma Scale (GCS) score and a brain Computerized Tomography (CT) scans were excluded. The cut-off value was considered 200 mg/dL to define hyperglycemia. Final GCS, hospital admission duration and complications were compared between normoglycemic and hyperglycemic patients. Results: Totally 217 patients were identified with TBI. Considering exclusion criteria, 89 patients remained for analysis. The mean age was 43.0±19.6 years, the mean time of remission was 5.9±9.4 hours, the mean GCS on admission was 10.5±3.6 and the mean blood glucose level in the first 24 hours was 138.1±59.4 mg/dL. Hyperglycemia was present in 13.5% of patients. The most common lesions presented by patients with TBI were fractures (22.5%), hematoma (18.3%), cerebral edema (18.3%) and cerebral contusion (16.2%). Most of patients without a high glucose level at admission were managed only medically, whereas surgical treatment was more frequent in patients with hyperglycemia (p=0.042). Hyperglycemia was associated with higher complication (p=0.019) and mortality rate (p=0.039). GCS was negatively associated with on admission glucose level (r=0.11; p=0.46). Conclusion: Hyperglycemia in the first 24-hours of TBI is associated with higher rate of surgical intervention, higher complication and mortality rates. So hyperglycemia handling is critical to the outcome of patients with traumatic brain injury. PMID:27162868

  7. Effects of Glycemic Level on Outcome of Patients with Traumatic Brain Injury: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Hernando Raphael Alvis-Miranda

    2014-04-01

    Full Text Available Objective: To determine the effects of glycemic level on outcome patients with traumatic brain injury. Methods: From September 2010 to December 2012, all medical records of adult patients with TBI admitted to the Emergency Room of Laura Daniela Clinic in Valledupar City, Colombia, South America were enrolled. Both genders between 18 and 85 years who referred during the first 48 hours after trauma, and their glucose level was determined in the first 24 hours of admission were included. Adults older than 85 years, with absence of Glasgow Coma Scale (GCS score and a brain Computerized Tomography (CT scans were excluded. The cut-off value was considered 200 mg/dL to define hyperglycemia. Final GCS, hospital admission duration and complications were compared between normoglycemic and hyperglycemic patients. Results: Totally 217 patients were identified with TBI. Considering exclusion criteria, 89 patients remained for analysis. The mean age was 43.0±19.6 years, the mean time of remission was 5.9±9.4 hours, the mean GCS on admission was 10.5±3.6 and the mean blood glucose level in the first 24 hours was 138.1±59.4 mg/dL. Hyperglycemia was present in 13.5% of patients. The most common lesions presented by patients with TBI were fractures (22.5%, hematoma (18.3%, cerebral edema (18.3% and cerebral contusion (16.2%. Most of patients without a high glucose level at admission were managed only medically, whereas surgical treatment was more frequent in patients with hyperglycemia (p=0.042. Hyperglycemia was associated with higher complication (p=0.019 and mortality rate (p=0.039. GCS was negatively associated with on admission glucose level (r=0.11; p=0.46. Conclusion: Hyperglycemia in the first 24-hours of TBI is associated with higher rate of surgical intervention, higher complication and mortality rates. So hyperglycemia handling is critical to the outcome of patients with traumatic brain injury.

  8. NT-brain natriuretic peptide levels in pleural fluid distinguish between pleural transudates and exudates.

    Science.gov (United States)

    Tomcsányi, János; Nagy, Erzsébet; Somlói, Miklós; Moldvay, Judit; Bezzegh, Attila; Bózsik, Béla; Strausz, János

    2004-10-01

    Pleural effusion is not pathognomic and distinguishing between transudates and exudates often presents a diagnostic dilemma. The purpose of our study was to examine whether the inclusion of pleural fluid brain natriuretic peptide (BNP) measurement into the analysis improves the diagnostic accuracy of pleural effusion. The pleural effusion of 14 patients with CHF (group A) and 14 subjects with different pleural pathology (group B) were analyzed. Samples of pleural fluid and serum were obtained from all patients on admission and biochemical analysis, bacterial and fungal culture, acid-fast bacilli smear and culture and cytology were performed on the pleural fluid. In vitro quantitative determination of N-terminal pro-Brain natriuretic peptide (NT-proBNP) in serum and pleural fluid were performed by electrochemiluminescence immunoassay proBNP method on an Elecsys 2010 (Roche) analyzer. The median NT-proBNP levels in groups A and B were 6295 pg/ml and 276 pg/ml, respectively: (P=0.0001). There was no overlap between the two groups. While the Light's criteria had a sensitivity of 93% and specificity of 43% for transudates, the pleural fluid NT-proBNP level accurately differentiated between the two groups. The pleural NT-proBNP levels were elevated in all patients who had transudate. Therefore if the NT-proBNP levels of pleural effusion are within the normal range, transudate resulting from congestive heart failure can be ruled out. Our results suggest that the inclusion of pleural fluid NT-proBNP measurement in the routine diagnostic panel would enhance discrimination among the different causes of pleural effusions.

  9. Facilitated catecholamine transport through bulk and polymer-supported liquid membranes

    NARCIS (Netherlands)

    Paugam, Marie-France; Bien, Jeffrey T.; Smith, Bradley D.; Chrisstoffels, L.A.J.; de Jong, Feike; Reinhoudt, David

    1996-01-01

    A series of crown boronic acids, 1-4, were synthesized and studied as carriers for catecholamine transport through bulk liquid membranes (BLMs) and supported liquid membranes (SLMs). Carrier 1 greatly facilitated the transport of primary catecholamines through BLMs; whereas, the more lipophilic anal

  10. Nutrients affecting brain composition and behavior

    Science.gov (United States)

    Wurtman, R. J.

    1987-01-01

    This review examines the changes in brain composition and in various brain functions, including behavior, that can follow the ingestion of particular foods or nutrients. It details those that are best understood: the increases in serotonin, catecholamine, or acetylcholine synthesis that can occur subsequent to food-induced increases in brain levels of tryptophan, tyrosine, or choline; it also discusses the various processes that must intervene between the mouth and the synapse, so to speak, in order for a nutrient to affect neurotransmission, and it speculates as to additional brain chemicals that may ultimately be found to be affected by changes in the availability of their nutrient precursors. Because the brain chemicals best known to be nutrient dependent overlap with those thought to underlie the actions of most of the drugs used to treat psychiatric diseases, knowledge of this dependence may help the psychiatrist to understand some of the pathologic processes occurring in his/her patients, particularly those with appetitive symptoms. At the very least, such knowledge should provide the psychiatrist with objective criteria for judging when to take seriously assertions that particular foods or nutrients do indeed affect behavior (e.g., in hyperactive children). If the food can be shown to alter neurotransmitter release, it may be behaviorally-active; however, if it lacks a discernible neurochemical effect, the likelihood that it really alters behavior is small.

  11. Chronic catecholamine depletion switches myocardium from carbohydrate to lipid utilisation.

    Science.gov (United States)

    Drake-Holland, A J; Van der Vusse, G J; Roemen, T H; Hynd, J W; Mansaray, M; Wright, Z M; Noble, M I

    2001-03-01

    Chronic cardiac transplantation denervation (i.e., global sympathetic denervation with myocardial catecholamine depletion, plus parasympathetic denervation) is known to inhibit myocardial oxidation of glucose. It is not known whether this is due to increased utilization of lactate, lipid or ketone bodies. The purpose of the present study was to test the hypothesis that the extraction and contribution of blood-borne fatty acids (FA) to overall oxidative energy conversion is increased. In anaesthetised dogs (control n = 6, cardiac denervated n = 6), we investigated fatty acid (FA) utilization. The studies were made at least four weeks after surgical cardiac denervation. Measurements were made of total FAs and with a radio-labelled tracer (U-14C palmitate). The contribution of FA utilisation to overall substrate oxidation rose from 31% (control) to 48% (cardiac denervated). The increase in the ratio (%) of CO2 production from palmitate oxidation to total CO2 production increased from 4.0 +/- 1.8 (control) to 10.6 +/- 5.8 (denervated, p = 0.04). The time from uptake of FA to release of CO2 product was unaltered. We conclude that the contribution of FA oxidation to overall energy conversion is increased in chronically denervated hearts, which is postulated to result from a decline in the active form of pyruvate dehydrogenase. This would appear to be a result of chronic catecholamine depletion.

  12. Hypersensitivity of lung vessels to catecholamines in systemic hypertension.

    Science.gov (United States)

    Guazzi, M D; Alimento, M; Fiorentini, C; Pepi, M; Polese, A

    1986-08-02

    Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper-reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over-reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure.

  13. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Correia

    2010-01-01

    Full Text Available OBJECTIVE: Blood neurotrophins, such as the brain-derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain-derived neurotrophic factor were evaluated in healthy individuals. METHODS: The concentric strengths of knee (large and elbow (small flexor and extensor muscles were measured on two separate days. Venous blood samples were obtained from 16 healthy subjects before and after exercise. RESULTS: The levels of brain-derived neurotrophic factor in the plasma did not significantly increase after both arm and leg exercise. There was no significant difference in the plasma levels of the brain-derived neurotrophic factor in the arms and legs. CONCLUSION: The present results demonstrate that acute strength exercise does not induce significant alterations in the levels of brain-derived neurotrophic factor plasma concentrations in healthy individuals. Considering that its levels may be affected by various factors, such as exercise, these findings suggest that the type of exercise program may be a decisive factor in altering peripheral brain-derived neurotrophic factor.

  14. [Catecholamines and their metabolites in children with Asperger and Kanner syndromes].

    Science.gov (United States)

    Gorina, A S; Kolesnichenko, L S; Mikhnovich, V I

    2011-01-01

    Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.

  15. Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine

    DEFF Research Database (Denmark)

    Artmann, Andreas; Petersen, Gitte; Hellgren, Lars

    2008-01-01

    acid in brain, jejunum and liver. The OA-diet increased brain levels of anandamide and oleoylethanolamide (not 2-arachidonoylglycerol) without changing tissue fatty acid composition. The same diet increased oleoylethanolamide in liver. All five dietary fats decreased oleoylethanolamide in jejunum...... (AA)) on tissue levels of 2-arachidonoylglycerol, anandamide, oleoylethanolamide, palmitoylethanolamide, stearoylethanolamide, linoleoylethanolamide, eicosapentaenoylethanolamide, docosahexaenoylethanolamide and tissue fatty acid composition. The LA-diet increased linoleoylethanolamide and linoleic...... without changing levels of anandamide, suggesting that dietary fat may have an orexigenic effect. The AA-diet increased anandamide and 2-arachidonoylglycerol in jejunum without effect on liver. The FO-diet decreased liver levels of all N-acylethanolamines (except eicosapentaenoylethanolamide...

  16. Potassium Aspartate Attenuates Brain Injury Induced by Controlled Cortical Impact in Rats Through Increasing Adenosine Triphosphate (ATP) Levels, Na+/K+-ATPase Activity and Reducing Brain Edema.

    Science.gov (United States)

    Gu, Yi; Zhang, Jie; Zhao, Yumei; Su, Yujin; Zhang, Yazhuo

    2016-12-13

    BACKGROUND Potassium aspartate (PA), as an electrolyte supplement, is widely used in clinical practice. In our previous study, we found PA had neuroprotective effects against apoptosis after cerebral ischemia/reperfusion in rats. In this study, we examine whether PA has protective effects on traumatic brain injury (TBI). MATERIAL AND METHODS TBI was induced by controlled cortical impact (CCI) in rats. Vehicle treatment (control) or PA treatment was administered intraperitoneally at 30 minutes after CCI. The modified neurological severity score (mNSS) and cortical lesion volume were examined. Brain edema and blood-brain barrier (BBB) integrity were measured, as well as brain ATP contents, lactic acid levels, and Na+/K+-ATPase activities. RESULTS We found that CCI induced cortical injury in rats. Acute PA treatment at the dose of 62.5 mg/kg and 125 mg/kg significantly improved neurological deficits (pATP (pATP levels, Na+/K+-ATPase activity, and reducing brain edema. It provides experimental evidence for the clinical application of PA.

  17. Multiphasic modification of intrinsic functional connectivity of the rat brain during increasing levels of propofol.

    Science.gov (United States)

    Liu, Xiping; Pillay, Siveshigan; Li, Rupeng; Vizuete, Jeannette A; Pechman, Kimberly R; Schmainda, Kathleen M; Hudetz, Anthony G

    2013-12-01

    The dose-dependent effects of anesthetics on brain functional connectivity are incompletely understood. Resting-state functional magnetic resonance imaging (rsfMRI) is widely used to assess the functional connectivity in humans and animals. Propofol is an anesthetic agent with desirable characteristics for functional neuroimaging in animals but its dose-dependent effects on rsfMRI functional connectivity have not been determined. Here we tested the hypothesis that brain functional connectivity undergoes specific changes in distinct neural networks at anesthetic depths associated with loss of consciousness. We acquired spontaneous blood oxygen level-dependent (BOLD) signals simultaneously with electroencephalographic (EEG) signals from rats under steady-state, intravenously administered propofol at increasing doses from light sedation to deep anesthesia (20, 40, 60, 80, and 100 mg/kg/h IV). Power spectra and burst suppression ratio were calculated from the EEG to verify anesthetic depth. Functional connectivity was determined from the whole brain correlation of BOLD data in regions of interest followed by a segmentation of the correlation maps into anatomically defined regional connectivity. We found that propofol produced multiphasic, dose dependent changes in functional connectivity of various cortical and subcortical networks. Cluster analysis predicted segregation of connectivity into two cortical and two subcortical clusters. In one cortical cluster (somatosensory and parietal), the early reduction in connectivity was followed by transient reversal; in the other cluster (sensory, motor and cingulate/retrosplenial), this rebound was absent. The connectivity of the subcortical cluster (brainstem, hippocampal and caudate) was strongly reduced, whereas that of another (hypothalamus, medial thalamus and n. basalis) did not. Subcortical connectivity increased again in deep anesthesia associated with EEG burst suppression. Regional correlation analysis confirmed the

  18. Rules rule! Brain activity dissociates the representations of stimulus contingencies with varying levels of complexity.

    Science.gov (United States)

    Tse, Chun-Yu; Low, Kathy A; Fabiani, Monica; Gratton, Gabriele

    2012-09-01

    The significance of stimuli is linked not only to their nature but also to the sequential structure in which they are embedded, which gives rise to contingency rules. Humans have an extraordinary ability to extract and exploit these rules, as exemplified by the role of grammar and syntax in language. To study the brain representations of contingency rules, we recorded ERPs and event-related optical signal (EROS; which uses near-infrared light to measure the optical changes associated with neuronal responses). We used sequences of high- and low-frequency tones varying according to three contingency rules, which were orthogonally manipulated and differed in processing requirements: A Single Repetition rule required only template matching, a Local Probability rule required relating a stimulus to its context, and a Global Probability rule could be derived through template matching or with reference to the global sequence context. ERP activity at 200-300 msec was related to the Single Repetition and Global Probability rules (reflecting access to representations based on template matching), whereas longer-latency activity (300-450 msec) was related to the Local Probability and Global Probability rules (reflecting access to representations incorporating contextual information). EROS responses with corresponding latencies indicated that the earlier activity involved the superior temporal gyrus, whereas later responses involved a fronto-parietal network. This suggests that the brain can simultaneously hold different models of stimulus contingencies at different levels of the information processing system according to their processing requirements, as indicated by the latency and location of the corresponding brain activity.

  19. Binding and release of brain calcium by low-level electromagnetic fields: A review

    Science.gov (United States)

    Adey, W. R.; Bawin, S. M.

    Evidence has accumulated that sensitivity of brain tissue to specific weak oscillating electromagnetic fields occurs in the absence of significant tissue heating (less than 0.1°C). This review focuses on the ‘windowed’ character of sensitivities of calcium binding and electrical activity in brain tissue to low-frequency modulation and intensity characteristics of impressed RF fields. ELF fields decrease calcium efflux from isolated chick and cat cerebral tissue by about 15% only in narrow amplitude and frequency ‘windows,’ between 6 and 20 Hz and between 10 and 100 V/m (approximate tissue gradient, 10-7 V/cm). VHF (147 MHz) and UHF (450 MHz) fields increase calcium efflux from isolated chick brain by about 15% when amplitude modulated between 6 and 20 Hz, but only for incident fields in the vicinity of 1.0 mW/cm2. We have now shown that this increased efflux in response to 16-Hz amplitude-modulated 450-MHz, 0.75-mW/cm2 field exposure is insensitive to variations in calcium concentration from 0 to 4.16 mM in the testing solution but is enhanced by addition of hydrogen ions (0.108 mM 0.1 N HCl) and inhibited in the absence of normal bicarbonate ion levels (2.4 mM). In the presence of lanthanum ions (2.0 mM), which block transmembrane movement of calcium, exposure to these EM fields decreases the 45Ca2 + efflux. Low-frequency gradients may be transduced in a specific class of extracellular binding sites, normally occupied by calcium ions and susceptible to competitive hydrogen ion binding. Transductive coupling may involve coherent charge states between anionic sites on membrane surface glycoproteins, with longrange cooperative interactions triggered by weak extracellular electric fields. Proton ‘tunneling’ may occur at boundaries between coherent and noncoherent charge zones.

  20. A comparison of brain gene expression levels in domesticated and wild animals.

    Directory of Open Access Journals (Sweden)

    Frank W Albert

    2012-09-01

    Full Text Available Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits. We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30-75 genes (less than 1% of expressed genes were differentially expressed, while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.

  1. Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Haoping; Wang, Hong; Ma, Shangwei; Xu, Yantong; Zhang, Han; Wang, Yuefei [Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae (China); Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin (China); Niu, Zichang [First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin (China); Fan, Guanwei; Zhu, Yan [Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae (China); Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin (China); Gao, Xiu Mei, E-mail: gaoxiumei@tjutcm.edu.cn [Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae (China); Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin (China)

    2014-01-01

    Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p < 0.01), while it reduced 300 μM acetylcholine (ACh) (p < 0.01), 100 μM veratridine (Ver) (p < 0.01) and 56 mM K{sup +} (p < 0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p < 0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56 mM K{sup +} induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p < 0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p < 0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects. - Highlights: • Bakuchiol stimulated basal catecholamine secretion. • Bakuchiol inhibited various secretagogues induced catecholamine secretion

  2. Cerebrospinal fluid biomarkers of central catecholamine deficiency in Parkinson's disease and other synucleinopathies.

    Science.gov (United States)

    Goldstein, David S; Holmes, Courtney; Sharabi, Yehonatan

    2012-06-01

    Central catecholamine deficiency characterizes α-synucleinopathies such as Parkinson's disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson's disease and two other synucleinopathies, multiple system atrophy and pure autonomic failure. Cerebrospinal fluid catechols were assayed in 146 subjects-108 synucleinopathy patients (34 Parkinson's disease, 54 multiple system atrophy, 20 pure autonomic failure) and 38 controls. In 14 patients cerebrospinal fluid was obtained before or within 2 years after the onset of parkinsonism. The Parkinson's disease, multiple system atrophy and pure autonomic failure groups all had lower cerebrospinal fluid dihydroxyphenylacetic acid [0.86 ± 0.09 (SEM), 1.00 ± 0.09, 1.32 ± 0.12 nmol/l] than controls (2.15 ± 0.18 nmol/l; P Parkinson's disease than in pure autonomic failure. Dihydroxyphenylacetic acid was 100% sensitive at 89% specificity in separating patients with recent onset of parkinsonism from controls but was of no value in differentiating Parkinson's disease from multiple system atrophy. Synucleinopathies feature cerebrospinal fluid neurochemical evidence for central dopamine and norepinephrine deficiency. Parkinson's disease and pure autonomic failure involve differential dopaminergic versus noradrenergic lesions. Cerebrospinal fluid dihydroxyphenylacetic acid seems to provide a sensitive means to identify even early Parkinson's disease.

  3. Repeated stress-induced stimulation of catecholamine response is not followed by altered immune cell redistribution.

    Science.gov (United States)

    Imrich, Richard; Tibenska, Elena; Koska, Juraj; Ksinantova, Lucia; Kvetnansky, Richard; Bergendiova-Sedlackova, Katarina; Blazicek, Pavol; Vigas, Milan

    2004-06-01

    Stress response is considered an important factor in the modulation of immune function. Neuroendocrine hormones, including catecholamines, affect the process of immune cell redistribution, important for cell-mediated immunity. This longitudinal investigation was aimed at evaluating the effect of repeated stress-induced elevation of catecholamines on immune cell redistribution and expression of adhesive molecules. We assessed the responses of epinephrine (EPI), norepinephrine (NE), cortisol, changes in lymphocytes subpopulations, and percentages of CD11a+, CD11b+, and CD62L+ lymphocytes to a 20-min treadmill exercise of an intensity equal to 80% of the individual's Vo(2)max. The exercise was performed before and after 6 weeks of endurance training consisting of a 1-h run 4 times a week (ET) and after 5 days of bed rest (HDBR) in 10 healthy males. We did not observe any significant changes in the basal levels of EPI, NE, and cortisol in the plasma, nor in the immune parameters after ET and HDBR. The exercise test led to a significant (P <.001) elevation of EPI and NE levels after both ET and HDBR, a significant elevation (P <.01) of cortisol after HDBR, an increase in the absolute numbers of leukocytes, granulocytes, monocytes, CD3+, CD4+, CD8+, CD16+, CD19+ lymphocytes, percentage of CD11a+ and CD11b+ lymphocytes, and to a decrease of CD62L1 before, after ET, and after HDBR. We found comparable changes in all measured immune parameters after ET and HDBR. In conclusion, repeated stress-induced elevation of EPI and NE was not associated with an alteration in immune cell redistribution found in response to the single bout of exercise.

  4. Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release.

    Science.gov (United States)

    Lee, Byung-Hwan; Kim, Jisu; Lee, Ra Mi; Choi, Sun-Hye; Kim, Hyeon-Joong; Hwang, Sung-Hee; Lee, Myung Koo; Bae, Chun-Sik; Kim, Hyoung-Chun; Rhim, Hyewon; Lim, Kiwon; Nah, Seung-Yeol

    2016-01-26

    Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina.

  5. Behavioral responses to catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa and healthy subjects.

    Science.gov (United States)

    Grob, Simona; Stern, Jair; Gamper, Lara; Moergeli, Hanspeter; Milos, Gabriella; Schnyder, Ulrich; Hasler, Gregor

    2015-04-01

    Bulimia nervosa (BN) has been associated with dysregulation of the central catecholaminergic system. An instructive way to investigate the relationship between catecholaminergic function and psychiatric disorder has involved behavioral responses to experimental catecholamine depletion (CD). The purpose of this study was to examine a possible catecholaminergic dysfunction in the pathogenesis of bulimia nervosa. CD was achieved by oral administration of alpha-methyl-para-tyrosine (AMPT) in 18 remitted female subjects with BN (rBN) and 31 healthy female control subjects. The study design consisted of a randomized, double blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were bulimic symptoms assessed by the Eating Disorder Examination-Questionnaire. Measures were assessed before and 26, 30, 54, 78, 102 hours after the first AMPT or placebo administration. In the experimental environment (controlled environment with a low level of food cues) rBN subjects had a greater increase in eating disorder symptoms during CD compared with healthy control subjects (condition × diagnosis interaction, p < .05). In the experimental environment, rBN subjects experienced fewer bulimic symptoms than in the natural environment (uncontrolled environment concerning food cues) 36 hours after the first AMPT intake (environment × diagnosis interaction, p < .05). Serum prolactin levels increased significantly, and to a comparable degree across groups, after AMPT administration. This study suggests that rBN is associated with vulnerability for developing eating disorder symptoms in response to reduced catecholamine neurotransmission after CD. The findings support the notion of catecholaminergic dysfunction as a possible trait abnormality in BN. © 2014 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  6. Time-dependent changes in serum biomarker levels after blast traumatic brain injury.

    Science.gov (United States)

    Gyorgy, Andrea; Ling, Geoffrey; Wingo, Daniel; Walker, John; Tong, Lawrence; Parks, Steve; Januszkiewicz, Adolph; Baumann, Richard; Agoston, Denes V

    2011-06-01

    Neuronal and glial proteins detected in the peripheral circulating blood after injury can reflect the extent of the damage caused by blast traumatic brain injury (bTBI). The temporal pattern of their serum levels can further predict the severity and outcome of the injury. As part of characterizing a large-animal model of bTBI, we determined the changes in the serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein (MBP), and neurofilament heavy chain (NF-H). Blood samples were obtained prior to injury and at 6, 24, 72 h, and 2 weeks post-injury from animals with different severities of bTBI; protein levels were determined using reverse phase protein microarray (RPPM) technology. Serum levels of S100B, MBP, and NF-H, but not NSE, showed a time-dependent increase following injury. The detected changes in S100B and MBP levels showed no correlation with the severity of the injury. However, serum NF-H levels increased in a unique, rapid manner, peaking at 6 h post-injury only in animals exposed to severe blast with poor clinical and pathological outcomes. We conclude that the sudden increase in serum NF-H levels following bTBI may be a useful indicator of injury severity. If additional studies verify our findings, the observed early peak of serum NF-H levels can be developed into a useful diagnostic tool for predicting the extent of damage following bTBI.

  7. Zinc transporters protein level in postmortem brain of depressed subjects and suicide victims.

    Science.gov (United States)

    Rafalo-Ulinska, Anna; Piotrowska, Joanna; Kryczyk, Agata; Opoka, Włodzimierz; Sowa-Kucma, Magdalena; Misztak, Paulina; Rajkowska, Grazyna; Stockmeier, Craig A; Datka, Wojciech; Nowak, Gabriel; Szewczyk, Bernadeta

    2016-12-01

    Major depressive disorder (MDD) is a serious psychiatric illness, associated with an increasing rate of suicide. The pathogenesis of depression may be associated with the disruption of zinc (Zn) homeostasis. In the brain, several proteins that regulate Zn homeostasis are present, including Zn transporters (ZnTs) which remove Zn from the cytosol. The present study was designed to investigate whether depression and suicide are associated with alterations in the expression of the ZnTs protein. Protein levels of ZnT1, ZnT3, ZnT4, ZnT5 and ZnT6 were measured in postmortem brain tissue from two different cohorts. Cohort A contained 10 subjects diagnosed with MDD (7 were suicide victims) and 10 psychiatrically-normal control subjects and cohort B contained 11 non-diagnosed suicide victims and 8 sudden-death control subjects. Moreover, in cohort A we measured protein level of NMDA (GluN2A subunit), AMPA (GluA1 subunit) and 5-HT1A receptors and PSD-95. Proteins were measured in the prefrontal cortex (PFC) using Western blotting. In addition, Zn concentration was measured using a voltammetric method. There was a significant increase in protein levels of ZnT1, ZnT4, ZnT5 in the PFC in MDD, relative to control subjects, while ZnT3 protein level was decreased in MDD. There was no significant difference in the Zn concentration in the PFC between control and MDD subjects. Similarly, in the PFC of suicide victims (non-diagnosed), an increase in protein levels of ZnT1, ZnT4, ZnT5 and ZnT6 was observed. Conversely, protein levels of ZnT3 were decreased in both suicide victims and subjects with MDD, in comparison with control subjects. There was also a significant decrease in the protein level of GluA1, GluN2A, PSD-95 and 5-HT1A in MDD. Our studies suggest that alterations in Zn transport proteins are associated with the pathophysiology of MDD and suicide. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. High fat diet and inflammation - modulation of Haptoglobin level in rat brain

    Directory of Open Access Journals (Sweden)

    Maria Stefania eSpagnuolo

    2015-12-01

    Full Text Available Obesity and dietary fats are well known risk factors for the pathogenesis of neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt is an acute phase protein, which acts as antioxidant by binding free Haemoglobin (Hb, thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neuroblastoma cell lines, beta-amyloid (Aβ uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks high-fat diet (HFD influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal level of TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr. Hpt concentration was lower (p<0.001 in hippocampus of HFD rats than in control animals, both in the 12 and in the 24 weeks fed groups. HFD was also associated in hippocampus with the increase of Hb level (p<0.01, inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. In fact, TNF-alpha concentration was higher in rats receiving HFD for 12 (p<0.01 or 24 weeks (p<0.001 compared to those receiving the control diet. N-Tyr concentration was more elevated in hippocampus of HFD than in control rats in both 12 weeks (p=0.04 and 24 weeks groups (p=0.01, and a positive correlation between Hb and N-Tyr concentration was found in each group. Finally, we found that the treatment of the human glioblastoma-astrocytoma cell line U-87 MG with cholesterol and fatty acids, such as palmitic and linoleic acid, significantly impairs (p<0.001 Hpt secretion in the extracellular compartment.We hypothesize that the HFD-dependent decrease of

  9. Nonselenium glutathione peroxidase in human brain : elevated levels in Parkinson's disease and dementia with lewy bodies.

    Science.gov (United States)

    Power, John H T; Shannon, John M; Blumbergs, Peter C; Gai, Wei-Ping

    2002-09-01

    Nonselenium glutathione peroxidase (NSGP) is a new member of the antioxidant family. Using antibodies to recombinant NSGP we have examined the distribution of this enzyme in normal, Parkinson's disease (PD), and dementia with Lewy body disease (DLB) brains. We have also co-localized this enzyme with alpha-synuclein as a marker for Lewy bodies. In normal brains there was a very low level of NSGP staining in astrocytes. In PD and DLB there were increases in the number and staining intensity of NSGP-positive astrocytes in both gray and white matter. Cell counting of NSGP cells in PD and DLB frontal and cingulated cortices indicated there was 10 to 15 times more positive cells in gray matter and three times more positive cells in white matter than in control cortices. Some neurons were positive for both alpha-synuclein and NSGP in PD and DLB, and double staining indicated that NSGP neurons contained either diffuse cytoplasmic alpha-synuclein deposits or Lewy bodies. In concentric Lewy bodies, alpha-synuclein staining was peripheral whereas NSGP staining was confined to the central core. Immunoprecipitation indicated there was direct interaction between alpha-synuclein and NSGP. These results suggest oxidative stress conditions exist in PD and DLB and that certain cells have responded by up-regulating this novel antioxidant enzyme.

  10. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

    2007-06-15

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  11. In vivo studies of low level laser (light) therapy for traumatic brain injury

    Science.gov (United States)

    Xuan, Weijun; Wu, Qiuhe; Huang, Ying-Ying; Ando, Takahiro; Huang, Liyi; Hamblin, Michael R.

    2012-03-01

    Low-level laser (or light) therapy (LLLT) is attracting growing interest to treat both stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain allows non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. It is proposed that red and NIR light is absorbed by chromophores in the mitochondria of cells leading to changes in gene transcription and upregulation of proteins involved in cell survival, antioxidant production, collagen synthesis, reduction of chronic inflammation and cell migration and proliferation. We developed a mouse model of controlled cortical impact (CCI) TBI and examined the effect of 0, 1, 3, and 14 daily 810-nm CW laser treatments in the CCI model as measured by neurological severity score and wire grip and motion test. 1 laser Tx gave a significant improvement while 3 laser Tx was even better. Surprisingly 14 laser Tx was no better than no treatment. Histological studies at necropsy suggested that the neurodegeneration was reduced at 14 days and that the cortical lesion was repaired by BrdU+ve neural progenitor (stem) cells at 28 days. Transcranial laser therapy is a promising treatment for acute (and chronic TBI) and the lack of side-effects and paucity of alternative treatments encourages early clinical trials.

  12. Alcohol-Binding Sites in Distinct Brain Proteins: The Quest for Atomic Level Resolution

    Science.gov (United States)

    Howard, Rebecca J.; Slesinger, Paul A.; Davies, Daryl L.; Das, Joydip; Trudell, James R.; Harris, R. Adron

    2011-01-01

    Defining the sites of action of ethanol on brain proteins is a major prerequisite to understanding the molecular pharmacology of this drug. The main barrier to reaching an atomic-level understanding of alcohol action is the low potency of alcohols, ethanol in particular, which is a reflection of transient, low-affinity interactions with their targets. These mechanisms are difficult or impossible to study with traditional techniques such as radioligand binding or spectroscopy. However, there has been considerable recent progress in combining X-ray crystallography, structural modeling, and site-directed mutagenesis to define the sites and mechanisms of action of ethanol and related alcohols on key brain proteins. We review such insights for several diverse classes of proteins including inwardly rectifying potassium, transient receptor potential, and neurotransmit-ter-gated ion channels, as well as protein kinase C epsilon. Some common themes are beginning to emerge from these proteins, including hydrogen bonding of the hydroxyl group and van der Waals interactions of the methylene groups of ethanol with specific amino acid residues. The resulting binding energy is proposed to facilitate or stabilize low-energy state transitions in the bound proteins, allowing ethanol to act as a “molecular lubricant” for protein function. We discuss evidence for characteristic, discrete alcohol-binding sites on protein targets, as well as evidence that binding to some proteins is better characterized by an interaction region that can accommodate multiple molecules of ethanol. PMID:21676006

  13. How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1

    Science.gov (United States)

    Serra, Laura; Petrucci, Antonio; Spanò, Barbara; Torso, Mario; Olivito, Giusy; Lispi, Ludovico; Costanzi-Porrini, Sandro; Giulietti, Giovanni; Koch, Giacomo; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2015-01-01

    Summary Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular impairment and brain dysfunctions. Although brain damage has previously been demonstrated in DM1, its associations with the genetics and clinical/neuropsychological features of the disease are controversial. This study assessed the differential role of gray matter (GM) and white matter (WM) damage in determining higher-level dysfunctions in DM1. Ten patients with genetically confirmed DM1 and 16 healthy matched controls entered the study. The patients underwent a neuropsychological assessment and quantification of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with studies including T1-weighted volumes and diffusion-weighted images. Voxel-based morphometry and tract-based spatial statistics were used for unbiased quantification of regional GM atrophy and WM integrity. The DM1 patients showed widespread involvement of both tissues. The extent of the damage correlated with CTG triplet expansion and cognition. This study supports the idea that genetic abnormalities in DM1 mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1. PMID:26214024

  14. Subclinical effects of groundwater contaminants. Pt. 4. Effects of repeated oral exposure to combinations of benzene and toluene on regional brain monoamine metabolism in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, G.C.; Parker, R.D.R. (Utah State Univ., Logan, UT (USA). Dept. of Biology); Sharma, R.P. (Utah State Univ., Logan, UT (USA). Dept. of Animal, Dairy and Veterinary Sciences)

    1990-11-01

    The effect of combined treatment with benzene and toluene on the endogenous concentrations of the catecholamines norepinephrine (NE) and dopamine (DA), the catecholamine metabolites vanillylmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the indoleamine serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), were investigated in six discrete brain regions of CD-1 mice. Groups of male, adult mice were continuously exposed to benzene (166 mg/l), toluene (80 and 325 mg/l), and combinations of benzene + toluene (80 or 325 mg/l) in drinking water for 4 weeks. Benzene produced increases of NE in the hypothalamus, cortex, midbrain and medulla oblongata, DA in the hypothalamus and corpus striatum, and 5-HT in all dissected brain regions except cerebellum. Elevated levels of various monoamine metabolites were also observed in these brain areas. Toluene ingestion alone also significantly increased the concentrations of NE, DA, 5-HT, and their metabolites in several brain regions. Mice given the combined treatments exhibited raised regional neurochemical levels when compared to the untreated controls. Increased concentrations of biogenic amine metabolites in several brain regions were greater in the combined exposures of benzene and toluene than when either chemical was used alone. The findings were different from those observed on immune parameters using similar treatment protocols, where simultaneous exposure to toluene prevented the immunotoxic effects of benzene. (orig./MG).

  15. Global brain blood-oxygen level responses to autonomic challenges in obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    Full Text Available Obstructive sleep apnea (OSA is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr, and 20 female (age 50.5±8.1 yrs and 37 male (age 45.6±9.2 yrs healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip, but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05. OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex

  16. Fasting levels of ghrelin covary with the brain response to food pictures.

    Science.gov (United States)

    Kroemer, Nils B; Krebs, Lena; Kobiella, Andrea; Grimm, Oliver; Pilhatsch, Maximilian; Bidlingmaier, Martin; Zimmermann, Ulrich S; Smolka, Michael N

    2013-09-01

    Ghrelin figures prominently in the regulation of appetite in normal-weighed individuals. The apparent failure of this mechanism in eating disorders and the connection to addictive behavior in general demand a deeper understanding of the endogenous central-nervous processes related to ghrelin. Thus, we investigated processing of pictures showing palatable food after overnight fasting and following a standardized caloric intake (i.e. a 75-g oral glucose tolerance test) using functional magnetic resonance imaging and correlated it with blood plasma levels of ghrelin. Twenty-six healthy female and male volunteers viewed food and control pictures in a block design and rated their appetite after each block. Fasting levels of ghrelin correlated positively with food-cue reactivity in a bilateral network of visual processing-, reward- and taste-related regions, including limbic and paralimbic regions. Notably, among those regions were the hypothalamus and the midbrain where ghrelin receptors are densely concentrated. In addition, high fasting ghrelin levels were associated with stronger increases of subjective appetite during the food-cue-reactivity task. In conclusion, brain activation and subjective appetite ratings suggest that ghrelin elevates the hedonic effects of food pictures. Thereby, fasting ghrelin levels may generally enhance subjective craving when confronted with reward cues.

  17. Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice.

    Science.gov (United States)

    Arendash, Gary W; Mori, Takashi; Cao, Chuanhai; Mamcarz, Malgorzata; Runfeldt, Melissa; Dickson, Alexander; Rezai-Zadeh, Kavon; Tane, Jun; Citron, Bruce A; Lin, Xiaoyang; Echeverria, Valentina; Potter, Huntington

    2009-01-01

    We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To determine if caffeine intake can have beneficial effects in "aged" APPsw mice already demonstrating cognitive impairment, we administered caffeine in the drinking water of 18-19 month old APPsw mice that were impaired in working memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the continuing impairment of control transgenic mice. In addition, Tg/Caff mice had substantially reduced Abeta deposition in hippocampus (decrease 40%) and entorhinal cortex (decrease 46%), as well as correlated decreases in brain soluble Abeta levels. Mechanistically, evidence is provided that caffeine suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined that caffeine concentrations within human physiological range effectively reduce active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory restoration and reversal of AD pathology, suggesting a treatment potential of caffeine in cases of established AD.

  18. Age influence on renalase and catecholamines concentration in hypertensive patients, including maintained dialysis

    Directory of Open Access Journals (Sweden)

    Zbroch E

    2016-10-01

    norepinephrine concentration (1.21 vs 0.87 ng/mL; P=0.008 in older patients of that population. In the dialysis subgroup, there were no differences between renalase and catecholamine level but older participants had lower diastolic blood pressure (69 vs 78 mmHg, P=0.001 and ejection fraction (51% vs 56.8%, P=0.03.Conclusion: The elevated renalase level in older hypertensive patients is related rather to kidney function and cardiovascular diseases than to age itself. Thus, renalase appears to be the possible new marker of these indications in this special population. Keywords: renalase, catecholamines, older age, hypertension, cardiovascular complications, chronic kidney disease

  19. Modeling the effects of noninvasive transcranial brain stimulation at the biophysical, network, and cognitive Level

    DEFF Research Database (Denmark)

    Hartwigsen, Gesa; Bergmann, Til Ole; Herz, Damian Marc

    2015-01-01

    Noninvasive transcranial brain stimulation (NTBS) is widely used to elucidate the contribution of different brain regions to various cognitive functions. Here we present three modeling approaches that are informed by functional or structural brain mapping or behavior profiling and discuss how...... predictions regarding the impact of interindividual variations in cortical anatomy on the injected electric fields or the influence of the orientation of current flow on the physiological stimulation effects. (ii) Functional brain mapping of the spatiotemporal neural dynamics during cognitive tasks can...

  20. Serum brain-derived neurotrophic factor levels in different neurological diseases.

    Science.gov (United States)

    Ventriglia, Mariacarla; Zanardini, Roberta; Bonomini, Cristina; Zanetti, Orazio; Volpe, Daniele; Pasqualetti, Patrizio; Gennarelli, Massimo; Bocchio-Chiavetto, Luisella

    2013-01-01

    Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF) in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD), 40 by Lewy body dementia (LBD), 91 by vascular dementia (VAD), 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients (P benzodiazepines (P = 0.020). In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects.

  1. Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    í Dali, Christine; Hanson, Lars G.; Barton, N. W.

    2010-01-01

    in oligodendrocytes and is known as a marker for neuronal and axonal loss. NAA and other metabolite levels measured by proton magnetic resonance spectroscopy (MRS) correlate with performance of the brain in normal children. There is a need for sensitive measures of disease progression in patients with MLD to enable...... development of future reatments. Methods: A cross-section of 13 children with late infantile MLD were examined by proton MRS. Signals from NAA, total choline, and total creatine in the deep white matter were measured and correlated with the results of cognitive and motor function tests. Results: The NAA...... signal decreased as the disease process advanced. Motor function, measured by the Gross Motor Function Measure–88, varied from 13 (only head movement in the supine position) to 180 (able to walk) across the study cohort, demonstrating a wide range in functional status. Similarly, varied decreases were...

  2. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Directory of Open Access Journals (Sweden)

    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  3. Brain docosahexaenoic acid (DHA levels of young rats are related to alpha-linolenic acid (ALA levels and fat matrix of the diet: impact of dairy fat*

    Directory of Open Access Journals (Sweden)

    Delplanque Bernadette

    2011-11-01

    Full Text Available Dososahexaenoate (DHA is highly concentrated in mammalian nervous and visual systems and its deficiency during gestation, lactation and early life, could have dramatic impacts on brain functions and mental health. Achieving an appropriate DHA status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how a-linolenic acid (ALA provided by different dietary fat matrices improved DHA content in the brains of both young male and female rats. Young rats born from dams fed during gestation and lactation with a low ALA diet (0.4% of fatty acids were subjected for 6 weeks after weaning to an anhydrous dairy fat blend-based diet that provided 1.5% ALA or to a palm oil blend-based diet that provided the same ALA level: either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid (ARA. With each diet the n-6/ n-3 ratio was similar (10 to follow the values generally recommended for infant formula. Fatty acids analysis in whole brain showed that 1.5% ALA dairy fat blend was superior to both 1.5% ALA palm-oil blends, supplemented or not with dietary DHA, for increasing brain DHA. Females compared to males had significantly higher brain DHA with the 1.5% ALA palm-blend diet, but the dietary supplementation with DHA smoothed the differences by a specific increase of males DHA brain. In conclusion, dairy fat blend enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of post-weaning rats. Inclusion of dairy fat in infant formulas should be reconsidered.

  4. Blast-Associated Shock Waves Result in Increased Brain Vascular Leakage and Elevated ROS Levels in a Rat Model of Traumatic Brain Injury.

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    Shushi Kabu

    Full Text Available Blast-associated shock wave-induced traumatic brain injury (bTBI remains a persistent risk for armed forces worldwide, yet its detailed pathophysiology remains to be fully investigated. In this study, we have designed and characterized a laboratory-scale shock tube to develop a rodent model of bTBI. Our blast tube, driven by a mixture of oxygen and acetylene, effectively generates blast overpressures of 20-130 psi, with pressure-time profiles similar to those of free-field blast waves. We tested our shock tube for brain injury response to various blast wave conditions in rats. The results show that blast waves cause diffuse vascular brain damage, as determined using a sensitive optical imaging method based on the fluorescence signal of Evans Blue dye extravasation developed in our laboratory. Vascular leakage increased with increasing blast overpressures and mapping of the brain slices for optical signal intensity indicated nonhomogeneous damage to the cerebral vasculature. We confirmed vascular leakage due to disruption in the blood-brain barrier (BBB integrity following blast exposure. Reactive oxygen species (ROS levels in the brain also increased with increasing blast pressures and with time post-blast wave exposure. Immunohistochemical analysis of the brain sections analyzed at different time points post blast exposure demonstrated astrocytosis and cell apoptosis, confirming sustained neuronal injury response. The main advantages of our shock-tube design are minimal jet effect and no requirement for specialized equipment or facilities, and effectively generate blast-associated shock waves that are relevant to battle-field conditions. Overall data suggest that increased oxidative stress and BBB disruption could be the crucial factors in the propagation and spread of neuronal degeneration following blast injury. Further studies are required to determine the interplay between increased ROS activity and BBB disruption to develop effective

  5. Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis

    DEFF Research Database (Denmark)

    Kaemmerer, Elke; Schneider, Ursula; Klaus, Christina

    2012-01-01

    Kaemmerer E, Schneider U, Klaus C, Plum P, Reinartz A, Adolf M, Renner M, Wolfs T G A M, Kramer B W, Wagner N, Mollenhauer J & Gassler N (2012) Histopathology Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis Aims:  Deleted in malignant brain...... in bacteria-related active intestinal inflammation such as appendicitis. Methods and results:  mRNA and protein levels of DMBT1 were analysed in surgical resections of 50 appendices (active inflammation: n = 25). In non-actively inflamed appendices, inter-individual differences in basal DMBT1 levels...

  6. Alteration of Plasma Brain Natriuretic Peptide Level After Acute Moderate Exercise in Professional Athletes

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    Homa Sheikhani

    2011-12-01

    Full Text Available Background: Cardiac fatigue or myocardial damage following exercise until complete exhaustion can increase blood levels of brain natriuretic peptide (BNP in athletes. Objectives: The aim of the present study was to investigate the effect of resistance and acute moderate aerobic exercise on alterations in BNP levels in professional athletes. Materials and Methods: Forty professional athletes who had at least 3 years of a championship background in track and field (aerobic group or body building (resistance group volunteered to participate in the present study. Track and field athletes (n = 20 were requested to run 8 km at 60% to 70% of maximum heart rate. Body building athletes (n = 20 performed a resistance training session of 5 exercises in 3 sets of 10 repetitions at 75% of 1 RM (bench press, seated row, leg extension, leg curl, and leg press. Before and immediately after the exercise, plasma BNP levels of both groups of athletes were measured by PATHFASTTM NT-proBNP assay, an immunochemiluminescent assay using two polyclonal antibodies in sandwich test format, on a PATHFASTTM automated analyzer. Results: Plasma BNP levels immediately following exercise increased significantly as compared with baseline values. Plasma BNP concentrations in the aerobic group were significantly higher than in the resistance group before and after exercise. Moreover, the increase in mean BNP concentrations in aerobic athletes was 7 times more than in resistance athletes. Conclusions: BNP levels in athlete who performed distance exercises increased significantly compared with resistance training. Possibly exercise program type, intensity of exercise, volume of exercise program, and field sport can be factors of changes in BNP levels

  7. Vascular Endothelial Growth Factor and Brain-Derived Neurotropic Factor Levels in Ischemic Stroke Subject

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    Andri Hidayat

    2016-08-01

    Full Text Available BACKGROUND: Vascular endothelial growth factor (VEGF and brain-derived neurotropic factor (BDNF present during early neuronal development and play important roles in the process of neurorepairing includes angiogenesis, neurogenesis and neuronal plasticity after ischemic stroke. In this study, we observed VEGF and BDNF levels of subjects with ischemic stroke in different onset time. METHODS: A cross sectional study was designed. Study subjects were 51 ischemic stroke subjects, aged 30-80 years old, recruited from Gatot Subroto Army Central Hospital, Jakarta, Indonesia. Ischemic stroke was diagnosed by neurologist, based on clinical examination and magnetic resonance imaging (MRI result. Subjects were divided into 3 groups based on onset time of stroke: 30 days (Group C. VEGF and BDNF levels from serum were measured using lumine Magpix. The data was analyzed for comparison and correlation. RESULTS: VEGF and BDNF levels of group B and C were significantly different with p=0.034 and p=0.007, respectively. Group B had the highest VEGF levels, whereas Group C had the highest BDNF level. VEGF and BDNF levels in each group were not significantly correlated. CONCLUSION: Each stage of time after ischemic stroke has different recovery activities like angiogenesis, neurogenesis and plasticity. Angiogenesis process was optimum in 7-30 days after onset. in more than 30 days onset, Low VEGF with high BDNF have important role in a long period of time after the onset of stroke in the regeneration and repair, such as maintaining neuronal survival and plasticity. KEYWORDS: ischemic stroke, VEGF, BDNF

  8. Biomarkers, mechanisms, and potential prevention of catecholamine neuron loss in Parkinson disease.

    Science.gov (United States)

    Goldstein, David S

    2013-01-01

    This chapter is on biomarkers, mechanisms, and potential treatment of catecholamine neuron loss in Parkinson disease (PD). PD is characterized by a movement disorder from loss of nigrostriatal dopamine neurons. An intense search is going on for biomarkers of the disease process. Theoretically, cerebrospinal fluid (CSF) levels of the deaminated DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), should be superior to other neurochemical indices of loss of central dopamine. CSF DOPAC is low in PD-even in patients with recent onset of Parkinsonism. Cardiac norepinephrine depletion is as severe as the loss of putamen dopamine. PD importantly involves nonmotor manifestations, including anosmia, dementia, REM behavior disorder, and orthostatic hypotension, and all of these nonmotor features are associated with neuroimaging evidence for cardiac sympathetic denervation, which seems to occur independently of the movement disorder and striatal dopaminergic lesion. Analogy to a bank robber's getaway car conveys the catecholaldehyde hypothesis, according to which buildup of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the immediate product of the action of monoamine oxidase on cytosolic dopamine, causes or contributes to the death of dopamine neurons. Decreased vesicular uptake of dopamine and decreased DOPAL detoxification by aldehyde dehydrogenase (ALDH) determine this buildup. Vesicular uptake is also markedly decreased in the heart in PD. Multiple factors influence vesicular uptake and ALDH activity. Evidence is accruing for aging-related induction of positive feedback loops and an autotoxic final common pathway in the death of catecholamine neurons, mediated by metabolites produced continuously in neuronal life. The catecholaldehyde hypothesis also leads to testable experimental therapeutic ideas.

  9. High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats.

    Science.gov (United States)

    Wu, Yingjen Jeffrey; Pagel, Michael A; Muldoon, Leslie L; Fu, Rongwei; Neuwelt, Edward A

    2017-08-01

    Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit-hyperactivity disorder (ADHD).

    Science.gov (United States)

    Scassellati, Catia; Zanardini, Roberta; Tiberti, Alessandra; Pezzani, Marco; Valenti, Vera; Effedri, Paola; Filippini, Elena; Conte, Stefano; Ottolini, Alberto; Gennarelli, Massimo; Bocchio-Chiavetto, Luisella

    2014-03-01

    It has been proposed that the neurotrophin brain-derived neurotrophic factor (BDNF) may be involved in attention deficit-hyperactivity disorder (ADHD) etiopathogenesis. Alterations in BDNF serum levels have been observed in childhood/adulthood neurodevelopmental pathologies, but no evidence is available for BDNF serum concentrations in ADHD. The study includes 45 drug-naïve ADHD children and 45 age-sex matched healthy subjects. Concentration of serum BDNF was determined by the ELISA method. BDNF serum levels in patients with ADHD were not different from those of controls (mean ± SD; ADHD: 39.33 ± 10.41 ng/ml; controls: 38.82 ± 8.29 ng/ml, t = -0.26, p = 0.80). Our findings indicate no alteration of serum BDNF levels in untreated patients with ADHD. A further stratification for cognitive, neuropsychological and psychopathological assessment in a larger sample could be useful to clarify the role of BDNF in the endophenotype characterization of ADHD.

  11. Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.

    Science.gov (United States)

    Bang, Shraddha R; Ambavade, Shirishkumar D; Jagdale, Priti G; Adkar, Prafulla P; Waghmare, Arun B; Ambavade, Prashant D

    2015-07-01

    Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease.

  12. Changes of Plasma Levels of Brain Natriuretic Peptide in Patients with Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    Pei Xiaoyang; Pan Ying; Hu Xuesong; Li Song; Xu Yawei; Yu Xuejing

    2006-01-01

    Objectives To investigate the changes of plasma brain natriuretic peptide (BNP) levels in patients with chronic heart failure (CHF).Methods Plasma BNP concentrations in patients with CHF (n=56) and in normal controls (n=60) were measured with specific radioimmunoassay. Left ventricular ejection fraction in patients with chronic heart failure was measured with 99mTc gated cardiac blood pool scintigraphy. Results The results showed that Plasma BNP concentrations in patients with CHF were significantly higher than normal controls (223±79 ng/L vs 40±15 ng/L, P < 0.01). Plasma BNP concentrations had a significant negative correlation with left ventricular ejection fractions(r=-0.68, P <0.01 ). Conclusions These results indicates that Plasma BNP levels are increased in patients with CHF, and they markedly increased according to the severity of heart failure classified by NYHA classification. The plasma BNP levels may be a biochemical parameter for evaluating the left ventricular function.

  13. Altered α-synuclein, parkin, and synphilin isoform levels in multiple system atrophy brains

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Winge, Kristian; Rasmussen, Nadja Bredo

    2016-01-01

    Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease-specific transcript......Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease......-specific transcription patterns in frontal cortex in PD, dementia with Lewy bodies, and MSA, and thus may mediate the development of α-synucleinopathies. In this study, the differential expression of α-synuclein isoforms on transcriptional and translational levels was ascertained in MSA patients in comparison with PD...... for parkin and synphilin-1 isoforms. In MSA brains, α-synuclein140 and α-synuclein 112 isoform levels were significantly increased, whereas levels of the α-synuclein 126 isoform were decreased in the substantia nigra, striatum, cerebellar cortex, and nucleus dentatus versus controls. Moreover, in MSA cases...

  14. Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats.

    Science.gov (United States)

    Wisniewski, Miriam S W; Carvalho-Silva, Milena; Gomes, Lara M; Zapelini, Hugo G; Schuck, Patrícia F; Ferreira, Gustavo C; Scaini, Giselli; Streck, Emilio L

    2016-04-01

    Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-chain α-ketoacids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. However, the effect of accumulating α-ketoacids in MSUD on neurotrophic factors has not been investigated. Thus, the objective of the present study was to evaluate the effects of acute intracerebroventricular administration of α-ketoisocaproic acid (KIC) on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brains of young male rats. Ours results showed that intracerebroventricular administration of KIC decreased BDNF levels in hippocampus, striatum and cerebral cortex, without induce a detectable change in pro-BDNF levels. Moreover, NGF levels in the hippocampus were reduced after intracerebroventricular administration of KIC. In conclusion, these data suggest that the effects of KIC on demyelination and memory processes may be mediated by reduced trophic support of BDNF and NGF. Moreover, lower levels of BDNF and NGF are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying the psychopathology of MSUD, supporting the hypothesis of a neurodegenerative process in MSUD.

  15. Spectrophotometric determination of catecholamine using vanadium and eriochrome cyanine r

    Energy Technology Data Exchange (ETDEWEB)

    Nagaraja, Padmarajaiah; Shrestha, Ashwinee Kumar; Shivakumar, Anantharaman; Al-Tayar, Naef Ghallab Saeed; Gowda, Avinask K., E-mail: profpn58@yahoo.co [University of Mysore, Manasagangotri (India). Dept. of Studies in Chemistry

    2011-07-01

    highly sensitive spectrophotometric method for the analysis of catecholamine drugs; L-dopa and methyldopa, is described. The analysis is based on the reaction of drug molecules with vanadium (V) which is reduced to vanadium (IV) and form complex with eriochrome cyanine R to give products having maximum absorbance ({lambda}{sub max}) at 565 nm. Beer's law is obeyed in the range 0.028-0.84 and 0.099-0.996 {mu}g mL{sup -1} for L-dopa and methyldopa, respectively. The statistical analysis as well as comparison with reported methods demonstrated high precision and accuracy of the proposed method. The method was successfully applied in the analysis of pharmaceutical preparations. (author)

  16. Possible modulatory effect of endogenous islet catecholamines on insulin secretion

    Directory of Open Access Journals (Sweden)

    Gagliardino Juan J

    2001-10-01

    Full Text Available Abstract Background The possible participation of endogenous islet catecholamines (CAs in the control of insulin secretion was tested. Methods Glucose-induced insulin secretion was measured in the presence of 3-Iodo-L-Tyrosine (MIT, a specific inhibitor of tyrosine-hydroxylase activity, in fresh and precultured islets isolated from normal rats. Incubated islets were also used to measure CAs release in the presence of low and high glucose, and the effect of α2-(yohimbine [Y] and idazoxan [I] and α1-adrenergic antagonists (prazosin [P] and terazosin [T] upon insulin secretion elicited by high glucose. Results Fresh islets incubated with 16.7 mM glucose released significantly more insulin in the presence of 1 μM MIT (6.66 ± 0.39 vs 5.01 ± 0.43 ng/islet/h, p Conclusion Our results suggest that islet-originated CAs directly modulate insulin release in a paracrine manner.

  17. Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

    Science.gov (United States)

    Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Chen-Chen; Sun, Hao; Sun, Shu-Qiang; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

    2017-08-01

    To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

  18. In vitro discrimination of the role of LRP1 at the BBB cellular level: focus on brain capillary endothelial cells and brain pericytes.

    Science.gov (United States)

    Candela, Pietra; Saint-Pol, Julien; Kuntz, Mélanie; Boucau, Marie-Christine; Lamartiniere, Yordenca; Gosselet, Fabien; Fenart, Laurence

    2015-01-12

    Several studies have demonstrated that the blood-brain barrier (BBB) (dynamic cellular complex composed by brain capillary endothelial cells (BCECs) and surrounded by astrocytic end feet and pericytes) regulates the exchanges of amyloid β (Aβ) peptide between the blood and the brain. Deregulation of these exchanges seems to be a key trigger for the brain accumulation of Aβ peptide observed in Alzheimer's disease (AD). Whereas the involvement of receptor for advanced glycation end-products in Aβ peptide transcytosis has been demonstrated in our laboratory, low-density lipoprotein receptor's role at the cellular level needs to be clarified. For this, we used an in vitro BBB model that consists of a co-culture of bovine BCECs and rat glial cells. This model has already been used to characterize low-density lipoprotein receptor-related peptide (LRP)'s involvement in the transcytosis of molecules such as tPA and angiopep-2. Our results suggest that Aβ peptide efflux across the BCEC monolayer involves a transcellular transport. However, the experiments with RAP discard an involvement of LRP family members at BCECs level. In contrast, our results show a strong transcriptional expression of LRP1 in pericytes and suggest its implication in Aβ endocytosis. Moreover, the observations of pericytes contraction and local downregulation of LRP1 in response to Aβ treatment opens up perspectives for studying this cell type with respect to Aβ peptide metabolism and AD. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats.

    Science.gov (United States)

    Conde, Silvia V; Nunes da Silva, Tiago; Gonzalez, Constancio; Mota Carmo, Miguel; Monteiro, Emilia C; Guarino, Maria P

    2012-01-01

    We tested the hypothesis that long-term caffeine intake prevents the development of insulin resistance and hypertension in two pathological animal models: the high-fat (HF) and the high-sucrose (HSu) diet rat. We used six groups of animals: control; caffeine-treated (Caff; 1 g/l in drinking water during 15 d); HF; caffeine-treated HF (HFCaff); HSu; caffeine-treated HSu (HSuCaff). Insulin sensitivity was assessed using the insulin tolerance test. Blood pressure, weight gain, visceral fat, hepatic glutathione, plasma caffeine, insulin and NO, and serum NEFA and catecholamines were measured. Caffeine reversed insulin resistance and hypertension induced by both the HF and HSu diets. In the HF-fed animals caffeine treatment restored fasting insulin levels to control values and reversed increased weight gain and visceral fat mass. In the HSu group, caffeine reversed fasting hyperglycaemia and restored NEFA to control values. There were no changes either in plasma NO or in hepatic glutathione levels. In contrast, caffeine totally prevented the increase in serum catecholamines induced by HF and HSu diets. To test the hypothesis that inhibition of the sympathetic nervous system prevents the development of diet-induced insulin resistance we administered carvedilol, an antagonist of β1, β2 and also α1 adrenoceptors, to HF and HSu rats. Carvedilol treatment fully prevented diet-induced insulin resistance and hypertension, mimicking the effect of caffeine. We concluded that long-term caffeine intake prevented the development of insulin resistance and hypertension in HF and HSu models and that this effect was related to a decrease in circulating catecholamines.

  20. Rats given linseed oil in microemulsion forms enriches the brain synaptic membrane with docosahexaenoic acid and enhances the neurotransmitter levels in the brain.

    Science.gov (United States)

    Sugasini, Dhavamani; Lokesh, Belur R

    2015-02-01

    Long chain n-3 fatty acids such as docosahexaenoic acid (DHA) are essential for the normal functioning of the brain. The vegetarian sections of the population get only alpha-linolenic acid (ALA) through their diet as a source of n-3 fatty acids. Hence, in this group of the population, the ALAs need to be converted to DHA through the action of the desaturase and the elongase enzymes. However, the conversion of the ALA to the DHA is very minimal (linseed oil (LSO) containing ALA. The rats were fed LSO as microemulsions in whey protein or in lipoid for 60 days through gavage. The rats given LSO microemulsions in lipoid showed higher levels of the DHA in the brain synaptic membrane when compared to rats given LSO without emulsion formation. This decreased the n-6/n-3 fatty acid ratio of the brain synaptic membrane. This also increased the membrane fluidity, Na⁺-K⁺ ATPase activity, and acetylcholine esterase activity in the synaptic membranes. Furthermore, Ca²⁺-Mg²⁺ ATPase activity, monoamine oxidase A and monoamine oxidase B activity was lowered in the rats given LSO in the microemulsion form. The dopamine and the serotonin levels in the brain were increased in the rats given LSO in the microemulsion form with lipoid as compared to those given LSO without the preemulsion formation. This study indicates that the LSO microemulsions in the lipoid can enhance the synaptic membrane DHA levels and influence the functions associated with the brain in a beneficial manner.

  1. Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ

    Directory of Open Access Journals (Sweden)

    Bogdan Lewczuk

    2014-07-01

    Full Text Available This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime.

  2. Soy peptide ingestion augments the synthesis and metabolism of noradrenaline in the mouse brain.

    Science.gov (United States)

    Imai, Haruka; Moriyasu, Kazuki; Nakahata, Akane; Maebuchi, Motohiro; Ichinose, Takashi; Furuya, Shigeki

    2017-05-01

    To examine whether edible peptide intake affects neurotransmitter metabolism in the brain, we evaluated the effect of peptides derived from soy proteins or fish collagen on free amino acids and monoamines in the mouse brain. Ingestion of soy peptides led to markedly higher levels of tyrosine, a catecholamine precursor, in the serum, and cerebral cortex compared to those following ingestion of vehicle alone or collagen peptides. Soy peptide ingestion also effectively increased 3-methoxy-4-hydroxyphenylethyleneglycol and normetanephrine, the principal metabolites of noradrenaline, in the cerebral cortex, hippocampus, and brainstem, whereas collagen peptides did not exert such effects. Further, soy peptide ingestion led to a significant increase in noradrenaline itself in the brainstem, where noradrenergic neurons are present. Noradrenergic turnover was also markedly stimulated in these regions after soy peptide ingestion. These in vivo observations suggest that soy peptide ingestion can maintain and promote the synthesis and metabolism of noradrenaline in the brain.

  3. Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages

    Science.gov (United States)

    Busanello, Anna; Bonini, Stefano; Quaranta, Luciano; Agnifili, Luca; Manni, Gianluca

    2017-01-01

    Purpose To investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters. Materials and Methods 45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated. Results Serum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03). Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019) and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04) but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06) compared to healthy controls. Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01). Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008) and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001) but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32) compared to healthy controls. BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004). Conclusions BDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that

  4. Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome

    Directory of Open Access Journals (Sweden)

    Akyol ES

    2015-03-01

    Full Text Available Esra Soydas Akyol,1 Yakup Albayrak,2 Murat Beyazyüz,3 Nurkan Aksoy,4 Murat Kuloglu,5 Kenji Hashimoto6 1Deparment of Psychiatry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 2Department of Psychiatry, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey; 3Department of Psychiatry, Biga State Hospital, Çanakkale, Turkey; 4Department of Biochemistry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 5Department of Psychiatry, Faculty of Medicine, Akdeniz University, Antalya, Turkey; 6Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Background: Brain-derived neurotrophic factor (BDNF is a well-established neurotrophin that plays a role in the pathophysiology of numerous psychiatric disorders. Many studies have investigated the serum BDNF levels in patients with schizophrenia. However, there are restricted data in the literature that compare the serum BDNF levels in patients with deficit and nondeficit syndromes. In this study, we aimed to compare the serum BDNF levels between schizophrenic patients with deficit or nondeficit syndrome and healthy controls.Methods: After fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia and 36 healthy controls were included in the study. The patients were grouped as deficit syndrome (N=23 and nondeficit syndrome (N=35 according to the Schedule for the Deficit Syndrome. Three groups were compared in terms of the sociodemographic and clinical variants and serum BDNF levels.Results: The groups were similar in terms of age, sex, body mass index, and smoking status. The serum BDNF levels in patients with deficit syndrome were significantly lower than those in healthy controls. In contrast, the serum BDNF levels in patients with nondeficit syndrome were similar to those in healthy controls.Conclusion: This study suggests that decreased BDNF levels may play a role in the pathophysio­logy of schizophrenic

  5. Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia.

    Science.gov (United States)

    Lo, Chun-Yi Zac; Su, Tsung-Wei; Huang, Chu-Chung; Hung, Chia-Chun; Chen, Wei-Ling; Lan, Tsuo-Hung; Lin, Ching-Po; Bullmore, Edward T

    2015-07-21

    Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.

  6. Electroencephalographic neurofeedback: Level of evidence in mental and brain disorders and suggestions for good clinical practice.

    Science.gov (United States)

    Micoulaud-Franchi, J-A; McGonigal, A; Lopez, R; Daudet, C; Kotwas, I; Bartolomei, F

    2015-12-01

    The technique of electroencephalographic neurofeedback (EEG NF) emerged in the 1970s and is a technique that measures a subject's EEG signal, processes it in real time, extracts a parameter of interest and presents this information in visual or auditory form. The goal is to effectuate a behavioural modification by modulating brain activity. The EEG NF opens new therapeutic possibilities in the fields of psychiatry and neurology. However, the development of EEG NF in clinical practice requires (i) a good level of evidence of therapeutic efficacy of this technique, (ii) a good practice guide for this technique. Firstly, this article investigates selected trials with the following criteria: study design with controlled, randomized, and open or blind protocol, primary endpoint related to the mental and brain disorders treated and assessed with standardized measurement tools, identifiable EEG neurophysiological targets, underpinned by pathophysiological relevance. Trials were found for: epilepsies, migraine, stroke, chronic insomnia, attentional-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, major depressive disorder, anxiety disorders, addictive disorders, psychotic disorders. Secondly, this article investigates the principles of neurofeedback therapy in line with learning theory. Different underlying therapeutic models are presented didactically between two continua: a continuum between implicit and explicit learning and a continuum between the biomedical model (centred on "the disease") and integrative biopsychosocial model of health (centred on "the illness"). The main relevant learning model is to link neurofeedback therapy with the field of cognitive remediation techniques. The methodological specificity of neurofeedback is to be guided by biologically relevant neurophysiological parameters. Guidelines for good clinical practice of EEG NF concerning technical issues of electrophysiology and of learning are suggested. These require validation by

  7. PCA and level set based non-rigid image registration for MRI and Paxinos-Watson atlas of rat brain

    Science.gov (United States)

    Cai, Chao; Liu, Ailing; Ding, Mingyue; Zhou, Chengping

    2007-12-01

    Image registration provides the ability to geometrically align one dataset with another. It is a basic task in a great variety of biomedical imaging applications. This paper introduced a novel three-dimensional registration method for Magnetic Resonance Image (MRI) and Paxinos-Watson Atlas of rat brain. For the purpose of adapting to a large range and non-linear deformation between MRI and atlas in higher registration accuracy, based on the segmentation of rat brain, we chose the principle components analysis (PCA) automatically performing the linear registration, and then, a level set based nonlinear registration correcting some small distortions. We implemented this registration method in a rat brain 3D reconstruction and analysis system. Experiments have demonstrated that this method can be successfully applied to registering the low resolution and noise affection MRI with Paxinos-Watson Atlas of rat brain.

  8. Decreased plasma brain-derived neurotrophic factor levels in institutionalized elderly with depressive disorder.

    Science.gov (United States)

    Chu, Chin-Liang; Liang, Chih-Kuang; Chou, Ming-Yueh; Lin, Yu-Te; Pan, Chih-Chuan; Lu, Ti; Chen, Liang-Kung; Chow, Philip C

    2012-06-01

    To compare the differences in plasma brain-derived neurotrophic factor (BDNF) levels among institutionalized ethnic Chinese elderly participants with major depression, those with subclinical depression, and a nondepressed control group. A cross-sectional study. The veterans' home in southern Taiwan. One hundred sixty-seven residents. Questionnaires including the Minimum Data Set Nursing Home 2.1, Chinese-language version, and the short-form Geriatric Depression Scale, Chinese-language version. Depressive disorder was diagnosed by a well-trained psychiatrist using DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria. We measured plasma BDNF levels in the following 3 groups: nondepressive subjects (n = 122), subclinically depressive subjects (n = 33), and subjects with major depression (n = 12). Plasma BDNF was assayed using the sandwich ELISA method. We noted a significantly negative association between age and plasma BDNF in the regression model. There was no significant correlation between BDNF plasma levels and body weight or platelet counts. We found that plasma BDNF was significantly lower in the major depressive group (mean, 115.1 pg/mL; SD, 57.2) than in the nondepressive group (mean, 548.8 pg/mL; SD, 370.6; P depressive group (mean, 231.8 pg/mL; SD, 92.4; P depressive disorder but also in those with subclinical depression. This makes the plasma BDNF level a potential biological marker for clinical or subclinical depression. Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  9. Serum Brain-Derived Neurotrophic Factor Levels in Different Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Mariacarla Ventriglia

    2013-01-01

    Full Text Available Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF in neurodegenerative disorders such as Alzheimer's disease (AD and Parkinson’s disease (PD. In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD, 40 by Lewy body dementia (LBD, 91 by vascular dementia (VAD, 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients (P<0.001 and a higher BDNF concentration in patients affected by PD (P=0.045. Analyses of effects of pharmacological treatments suggested significantly higher BDNF serum levels in patients taking mood stabilizers/antiepileptics (P=0.009 and L-DOPA (P<0.001 and significant reductions in patients taking benzodiazepines (P=0.020. In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects.

  10. Enhanced zinc consumption causes memory deficits and increased brain levels of zinc

    Science.gov (United States)

    Flinn, J.M.; Hunter, D.; Linkous, D.H.; Lanzirotti, A.; Smith, L.N.; Brightwell, J.; Jones, B.F.

    2005-01-01

    Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (??SXRF) confirmed that brain zinc levels were increased by adding ZnCO 3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function. ?? 2004 Elsevier Inc. All rights reserved.

  11. DNA methylation levels of α-synuclein intron 1 in the aging brain.

    Science.gov (United States)

    de Boni, Laura; Riedel, Linda; Schmitt, Ina; Kraus, Theo F J; Kaut, Oliver; Piston, Dominik; Akbarian, Schahram; Wüllner, Ullrich

    2015-12-01

    DNA methylation patterns change with age, and aging itself is a major confounding risk factor for Parkinson's disease (PD). Duplication and triplication, that is, increased expression of the α-synuclein (SNCA) gene, cause familial PD, and demethylation of SNCA intron 1 has been shown to result in increased expression of SNCA. We thus hypothesized that age-related alterations of SNCA methylation might underly the increased susceptibility toward PD in later life. The present study sought to determine (1) whether alterations of SNCA intron 1 methylation occurred during aging, (2) whether the methylation pattern differed between men and women, and (3) whether purified neurons compared with non-neuronal cells exhibited different methylation patterns. The analysis of DNA from brain tissue and fluorescence activated cell sorting-sorted purified neurons of 41 individuals revealed only a minor increase of SNCA intron 1 DNA methylation levels in presumably healthy individuals during aging but no significant difference between men and women. Interestingly enough, methylation of SNCA intron 1 was higher in neurons compared with non-neuronal cells, although non-neuronal cells express lower levels of SNCA. Therefore, the normal pattern of SNCA methylation during aging should not result in increased expression of α-synuclein protein. It is thus likely that additional, yet not identified, mechanisms contribute to the tissue specificity of SNCA expression and the presumed dysregulation in PD.

  12. Theoretical model for mesoscopic-level scale-free self-organization of functional brain networks.

    Science.gov (United States)

    Piersa, Jaroslaw; Piekniewski, Filip; Schreiber, Tomasz

    2010-11-01

    In this paper, we provide theoretical and numerical analysis of a geometric activity flow network model which is aimed at explaining mathematically the scale-free functional graph self-organization phenomena emerging in complex nervous systems at a mesoscale level. In our model, each unit corresponds to a large number of neurons and may be roughly seen as abstracting the functional behavior exhibited by a single voxel under functional magnetic resonance imaging (fMRI). In the course of the dynamics, the units exchange portions of formal charge, which correspond to waves of activity in the underlying microscale neuronal circuit. The geometric model abstracts away the neuronal complexity and is mathematically tractable, which allows us to establish explicit results on its ground states and the resulting charge transfer graph modeling functional graph of the network. We show that, for a wide choice of parameters and geometrical setups, our model yields a scale-free functional connectivity with the exponent approaching 2, which is in agreement with previous empirical studies based on fMRI. The level of universality of the presented theory allows us to claim that the model does shed light on mesoscale functional self-organization phenomena of the nervous system, even without resorting to closer details of brain connectivity geometry which often remain unknown. The material presented here significantly extends our previous work where a simplified mean-field model in a similar spirit was constructed, ignoring the underlying network geometry.

  13. Pentoxifylline attenuates TNF-α protein levels and brain edema following temporary focal cerebral ischemia in rats.

    Science.gov (United States)

    Vakili, Abedin; Mojarrad, Somye; Akhavan, Maziar Mohammad; Rashidy-Pour, Ali

    2011-03-04

    Cerebral edema is the most common cause of neurological deterioration and mortality during acute ischemic stroke. Despite the clinical importance of cerebral ischemia, the underlying mechanisms remain poorly understood. Recent studies suggest a role for TNF-α in the brain edema formation. To further investigate whether TNF-α would play a role in brain edema formation, we examined the effects of pentoxifylline (PTX, an inhibitor of TNF-α synthesis) on the brain edema and TNF-α levels in a model of transient focal cerebral ischemia. The right middle cerebral artery (MCA) of rats was occluded for 60 min using the intraluminal filament method. The animals received PTX (60 mg/kg) immediately, 1, 3, or 6h post-ischemic induction. Twenty-four hours after induction of ischemic injury, permeability of the blood-brain barrier (BBB) and brain edema were determined by in situ brain perfusion of Evans Blue (EB) and wet-to-dry weight ratio, respectively. TNF-α protein levels in ischemic cortex were also measured at 1, 4, and 24h after the beginning of an ischemic stroke by using an enzyme-linked immunosorbent assay method. The administration of PTX up to 6h after occlusion of the MCA significantly reduced the brain edema. Moreover, PTX significantly reduced the concentration of TNF-α in ischemic brain cortex up to 4h post-transient focal stroke (Pedema in a model of transient focal cerebral ischemia. The beneficial effects of PTX may be mediated, at least in part, through a decline in TNF-α production and BBB breakdown.

  14. N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

    Science.gov (United States)

    Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

    2017-09-01

    The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

  15. The brain responses to different frequencies of binaural beat sounds on QEEG at cortical level.

    Science.gov (United States)

    Jirakittayakorn, Nantawachara; Wongsawat, Yodchanan

    2015-01-01

    Beat phenomenon is occurred when two slightly different frequency waves interfere each other. The beat can also occur in the brain by providing two slightly different frequency waves separately each ear. This is called binaural beat. The brain responses to binaural beat are in discussion process whether the brain side and the brain area. Therefore, this study aims to figure out the brain responses to binaural beat by providing different binaural beat frequencies on 250 carrier tone continuously for 30 minutes to participants and using quantitative electroencephalography (QEEG) to interpret the data. The result shows that different responses appear in different beat frequency. Left hemisphere dominance occur in 3 Hz beat within 15 minutes and 15 Hz beat within 5 minutes. Right hemisphere dominance occurs in 10 Hz beat within 25 minute. 6 Hz beat enhances all area of the brain within 10 minutes. 8 Hz and 25 Hz beats have no clearly responses while 40 Hz beat enhances the responses in frontal lobe. These brain responses can be used for brain modulation application to induce the brain activity in further studies.

  16. EFFECT OF ACUPUNCTURE COMBINED WITH EPIDURAL ANESTHESIA ON PLASMA CATECHOLAMINE CONTENT IN CHOLECYSTECTOMY PATIENTS

    Institute of Scientific and Technical Information of China (English)

    Li Changgen; Peng Xiaoyun; Xu Mingyu; Wang Zhongcheng

    2001-01-01

    Objective: To observe changes of plasma catecholamine (CA) level in patients experiencing cholecystectomy under acupuncture anesthesia combined with epidural administration of small dose of anesthetics. Methods:33 cholecystectomy patients were randomly divided into acupuncture combined with epidural anesthesia (A) group (n = 11), acupoint-skin electrical stimulation combined with epidural anesthesia (B) group (n= 11 ) and simple epidural anesthesia (C) group (n= 11). Acupoints used were bilateral Zusanli (ST 36) and Neiguan (PC 6) and stimulated with parameters of frequency 2/15 Hz, intermittent waves, electric current 2~3 mA for group A and 13mA for group B. Extradural anesthetic administered was 1.5% Lidocaine 5 mL. Venous blood samples were collected one day before,NE of group A and B lowered in comparison with pre-operation, particularly group A (P <0.01), while in group C,plasma NE level increased slightly; plasma E of group A and B increased significantly compared with pre-operation (P levels recovered basically in comparison with those of one day before operation. It indicates that acupuncture or acupoint-skin electrical stimulation is capable of regulating sympathetic activity during epidural anesthesia. The anesthetic effec t has a closer relation with changes of plasma NE level rather than changes of plasma E or DA levels. C_onclusion:Acupuncture or acupoint-surface electrical stimulation combined with epidural anesthesia may be of reducing or releasing surgical operation generated stress response during cholecystectomy.

  17. EFFECTS OF CHRONIC STRESS ON THE ACTIVITIES OF SOD, GSH-Px AND MDA LEVEL IN FEMALE RATS' BRAIN

    Institute of Scientific and Technical Information of China (English)

    王莹; 杨东伟; 谢雯; 庞炜; 蒋马莉; 韩太真

    2002-01-01

    Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats' brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased (P<0.05 and P<0.01, respectively) while the MDA level increased (P<0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased (P<0.05) while the activity in E increased (P<0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats' brain.

  18. Physiological mouse brain Abeta levels are not related to the phosphorylation state of threonine-668 of Alzheimer's APP.

    Directory of Open Access Journals (Sweden)

    Yoshitake Sano

    Full Text Available BACKGROUND: Amyloid-beta peptide species ending at positions 40 and 42 (Abeta40, Abeta42 are generated by the proteolytic processing of the Alzheimer's amyloid precursor protein (APP. Abeta peptides accumulate in the brain early in the course of Alzheimer's disease (AD, especially Abeta42. The cytoplasmic domain of APP regulates intracellular trafficking and metabolism of APP and its carboxyl-terminal fragments (CTFalpha, CTFbeta. The role of protein phosphorylation in general, and that of the phosphorylation state of APP at threonine-668 (Thr668 in particular, has been investigated in detail by several laboratories (including our own. Some investigators have recently proposed that the phosphorylation state of Thr668 plays a pivotal role in governing brain Abeta levels, prompting the current study. METHODOLOGY: In order to evaluate whether the phosphorylation state of Thr668 controlled brain Abeta levels, we studied the levels and subcellular distributions of holoAPP, sAPPalpha, sAPPbeta, CTFalpha, CTFbeta, Abeta40 and Abeta42 in brains from "knock-in" mice in which a non-phosphorylatable alanyl residue had been substituted at position 668, replacing the threonyl residue present in the wild-type protein. CONCLUSIONS: The levels and subcellular distributions of holoAPP, sAPPalpha, sAPPbeta, CTFalpha, CTFbeta, Abeta40 and Abeta42 in the brains of Thr668Ala mutant mice were identical to those observed in wild-type mice. These results indicate that, despite speculation to the contrary, the phosphorylation state of APP at Thr668 does not play an obvious role in governing the physiological levels of brain Abeta40 or Abeta42 in vivo.

  19. Comparison of blood-oxygen-level-dependent functional magnetic resonance imaging and near-infrared spectroscopy recording during functional brain activation in patients with stroke and brain tumors.

    Science.gov (United States)

    Sakatani, Kaoru; Murata, Yoshihiro; Fujiwara, Norio; Hoshino, Tatsuya; Nakamura, Shin; Kano, Tsuneo; Katayama, Yoichi

    2007-01-01

    Blood-oxygen-level-dependent contrast functional magnetic resonance imaging (BOLD-fMRI) has been used to perform functional imaging in brain disorders such as stroke and brain tumors. However, recent studies have revealed that BOLD-fMRI does not image activation areas correctly in such patients. To clarify the characteristics of the evoked cerebral blood oxygenation (CBO) changes occurring in stroke and brain tumors, we have been comparing near-infrared spectroscopy (NIRS) and BOLD-fMRI recording during functional brain activation in these patients. We review our recent studies and related functional imaging studies on the brain disorders. In the primary sensorimotor cortex (PSMC) on the nonlesion side, the motor task consistently caused a decrease of deoxyhemoglobin (deoxy-Hb) with increases of oxyhemoglobin (oxy-Hb) and total hemoglobin (t-Hb), which is consistent with the evoked CBO response observed in normal adults. BOLD-fMRI demonstrated robust activation areas on the nonlesion side. In stroke patients, severe cerebral ischemia (i.e., misery perfusion) caused an increase of deoxy-Hb during the task, associated with increases of oxy-Hb and t-Hb, in the PSMC on the lesion side. In addition, the activation volume of BOLD-fMRI was significantly reduced on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side, but it tended to decrease in other areas during the tasks. In brain tumors, BOLD-fMRI clearly demonstrated activation areas in the PSMC on the lesion side in patients who displayed a normal evoked CBO response. However, the activation volume on the lesion side was significantly reduced in patients who exhibited an increase of deoxy-Hb during the task. In both stroke and brain tumors, false-negative activations (i.e., marked reductions of activation volumes) in BOLD imaging were associated with increases of deoxy-Hb, which could cause a reduction in BOLD signal. BOLD-fMRI investigations of patients with brain disorders

  20. Transcranial low-level laser therapy increases memory, learning, neuroprogenitor cells, BDNF and synaptogenesis in mice with traumatic brain injury

    Science.gov (United States)

    Xuan, Weijun; Huang, Liyi; Vatansever, Fatma; Agrawal, Tanupriya; Hamblin, Michael R.

    2015-03-01

    Increasing concern is evident over the epidemic of traumatic brain injury in both civilian and military medicine, and the lack of approved treatments. Transcranial low level laser therapy tLLLT) is a new approach in which near infrared laser is delivered to the head, penetrates the scalp and skull to reach the brain. We asked whether tLLLT at 810-nm could improve memory and learning in mice with controlled cortical impact traumatic brain injury. We investigated the mechanism of action by immunofluorescence studies in sections from brains of mice sacrificed at different times. Mice with TBI treated with 1 or 3 daily laser applications performed better on Morris Water Maze test at 28 days. Laser treated mice had increased BrdU incorporation into NeuN positive cells in the dentate gyrus and subventricular zone indicating formation of neuroprogenitor cells at 7 days and less at 28 days. Markers of neuron migration (DCX and Tuj1) were also increased, as was the neurotrophin, brain derived neurotrophic factor (BDNF) at 7 days. Markers of synaptogenesis (formation of new connections between existing neurons) were increased in the perilesional cortex at 28 days. tLLLT is proposed to be able to induce the brain to repair itself after injury. However its ability to induce neurogenesis and synaptogenesis suggests that tLLLT may have much wider applications to neurodegenerative and psychiatric disorders.

  1. Association between plasma brain natriuretic peptide/N-terminal pro-brain natriuretic peptide levels and atrial fibrillation:evidence from a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Liu Yaowu; Xiao Yunyun; Chen Xinguang; Zhang Fengxiang

    2014-01-01

    Background Several small sample-size observational studies evaluated the association of plasma brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) with atrial fibrillation (AF),but the results were contradictory.We aimed to perform a meta-analysis of relevant studies to evaluate the availability of this association.Methods We performed an extensive literature search on PubMed,Web of Science (WOS) and the Cochrane Library databases.Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to assess the strength of association using random effects models.We performed sensitivity and subgroup analyses to explore the potential sources of heterogeneity.We also estimated publication biases.Statistical analyses were performed using the STATA 12.0 software.Results A total of 11 studies including 777 cases and 870 controls were finally analyzed.Overall,the brain natriuretic peptide/N-terminal pro-brain natriuretic peptide levels were higher in atrial fibrillation patients than controls without atrial fibrillation.Results showed that the SMD in the natriuretic peptide levels between cases and controls was 2.68 units (95%CI 1.76 to 3.60); test for overall effect z-score=5.7 (P <0.001).There was significant heterogeneity between individual studies (I2=97.8%; P <0.001).Further analysis revealed that differences in the assay of natriuretic peptide possibly account for this heterogeneity.Conclusions Increased BNP/NT-proBNP levels were associated with the presence of atrial fibrillation.This finding indicates that BNP/NT-proBNP may prove to be a biomarker of an underlying predisposition to AF.

  2. Methodological considerations to determine the effect of exercise on brain-derived neurotrophic factor levels

    OpenAIRE

    Pareja Galeano, Helios; Alis, Rafael; Sanchís-Gomar, Fabián; Cabo, Helena; Cortell-Ballester, José; Gómez Cabrera, María del Carmen; Lucía Mulas, Alejandro; Viña, José

    2015-01-01

    Physical exercise up-regulates brain-derived neurotrophic factor (BDNF) in the brain and blood. However, there is yet no consensus about the adequate blood processing conditions to standardize its assessment. We aimed to find a reliable blood sample processing method to determine changes in BDNF due to exercise. 2.382 JCR (2015) Q2, 9/30 Medical laboratory technology UEM

  3. The study of low level laser irradiation therapy on brain infarction with SPECT

    Institute of Scientific and Technical Information of China (English)

    Xiao Xuechang; Jia Shaowei; Zleng Xiyuan

    2000-01-01

    Objective: Effect of rCBF and brain function on ILIB treating brain infarction will be investigated by SPECT brain perfusion imaging. Method: 3 1 patients with brain infarction, 17 patients were treated by ILIB on standard pharmaceutial treatment. SPECT brain perfusion imaging was performed before and after ILIB therapy with comparison of oneself. They were quantified with BFCR% model effect during ILIB in 14 patients were observed. Result: ILIB 30 rnme SPECT showed the improvement of rCBF and cerebral function in 14 patients with brain infarction, and in 17 patients locus were prominence than mirror regions att er ILIB therapy, both are higher singnitficant difference ( t=4.4052, P<0.0001 ), but mirror regions were not singnificant difference before and after ILIB (t=1.6995, P>0.05). BFCR% quantitative results of locus were higher mirror regions, and higher singnificant difference (t=4.5278 p<0.0001 )。 Conclusion: ILIB can improve the rCBF and cerebral function of patients with brain infarction, and provoke function of brain cells. Some new evidence was provided for ILIB treatment of cerebral ischemia

  4. DIFFERENTIAL MODULATION OF CATECHOLAMINES BY CHLOROTRIAZINE HERBICIDES IN PHEOCHROMOCYTOMA (PC12) CELLS IN VITRO

    Science.gov (United States)

    Differential modulation of catecholamines by chlorotriazine herbicides in pheochromocytoma (PC12) cells in vitro.Das PC, McElroy WK, Cooper RL.Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599, USA.Epidemiological, wildlife, and lab...

  5. Age at diagnosis of pheochromocytoma differs according to catecholamine phenotype and tumor location

    NARCIS (Netherlands)

    Eisenhofer, G.; Timmers, H.J.L.M.; Lenders, J.W.M.; Bornstein, S.R.; Tiebel, O.; Mannelli, M.; King, K.S.; Vocke, C.D.; Linehan, W.M.; Bratslavsky, G.; Pacak, K.

    2011-01-01

    CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are diagnosed earlier in patients with hereditary than sporadic disease. Whether other factors influence age at diagnosis is unclear. OBJECTIVE: We examined ages at which PPGLs were diagnosed according to different catecholamine phenotypes and

  6. Stability of urinary fractionated metanephrines and catecholamines during collection, shipment, and storage of samples.

    NARCIS (Netherlands)

    Willemsen, J.J.; Ross, H.A.; Lenders, J.W.M.; Sweep, C.G.J.

    2007-01-01

    BACKGROUND: Measurements of 24-h fractionated urinary metanephrines and catecholamines are used for the diagnosis of pheochromocytoma, but adequate information is needed regarding collection, storage, and shipment conditions. METHODS: Spot urine samples were collected from 8 healthy volunteers. Aliq

  7. Effects of morphine dependence and withdrawal on levels of neurosteroids in rat brain

    Institute of Scientific and Technical Information of China (English)

    Cai-zhen YAN; Yan-ning HOU

    2004-01-01

    AIM: To investigate the effects of morphine dependence and withdrawal on the concentrations of neurosteroids in rat brain. METHODS: A method of simultaneous quantification of neurosteroids by gas chromatography-mass spectrometry (GC-MS) had been established. RESULTS: The chronic morphine administration (ip) resulted in a marked decrease in the brain concentrations of pregnenolone (PREG), progesterone (PROG), and pregenenolone sulfate (PREGS) in rats killed 6 h after the last treatment. In contrast, there were no significant effects of morphine dependence on the brain concentrations of allopregnanolone (AP), dihydroepiandrosterone (DHEA), and dihydroepiandrosterone sulfate (DHEAS). Naloxone-induced withdrawal produced a significant increase in the concentrations of PREG, PROG, AP, DHEA, PREGS, and DHEAS as compared with the control group.CONCLUSION: Morphine dependence and withdrawal affected the concentrations of neurosteroids in rat brain,which suggests that endogenous neurosteroids in brain might be related to the development of morphine dependence and withdrawal.

  8. VERP and brain imaging for identifying levels of visual dorsal and ventral stream function in typical and preterm infants.

    Science.gov (United States)

    Braddick, Oliver; Atkinson, Janette; Wattam-Bell, John

    2011-01-01

    Visual development is a key area for understanding and assessing early brain development. Different levels in the hierarchy of visual processing, from the initial response to flashes of light, through selective responses to contour orientation and motion in primary visual cortex (V1), to global processing in extrastriate of large-scale patterns of form and motion, can each be assessed using stimuli designed to isolate specific neural activity in visual event-related potentials (VERPs). This approach has been used to reveal the sequence of emergence of different visual cortical functions in the first 6 months of typical human development, and to provide early indicators of anomalies in brain development. Delayed or absent onset of orientation-reversal (OR-)VERPs, as a measure of cortical development, has been shown to be a sensitive indicator of perinatal brain damage in both term-born and prematurely born infants. Direction-reversal (DR-)VERPs appear a few weeks later than OR-VERPs in typical development, and are further delayed in even healthy children born preterm, reflecting possible early vulnerability of the motion (dorsal stream) system. High-density recordings of responses to global motion and global form patterns show that these extrastriate systems are typically functional by 5 months of age, but the topography of the activity distributions shows that the brain systems underlying these responses are radically reorganized between infancy and adulthood. In prematurely born infants whose structural brain MRI was evaluated at birth, the onset of the response is absent or delayed in those with severe brain injury, while in those with mild/moderate brain injury the response is present but its spatial organization is further from the adult pattern than those in controls. These findings are related to the development of distinct networks of brain areas in the dorsal and ventral cortical streams, and the apparent vulnerability of the dorsal-stream network in a wide

  9. Retinoic acid reverses the PTU related decrease in neurogranin level in mice brain.

    Science.gov (United States)

    Enderlin, V; Vallortigara, J; Alfos, S; Féart, C; Pallet, V; Higueret, P

    2004-09-01

    Recent data have shown that fine regulation of retinoid mediated gene expression is fundamentally important for optimal brain functioning in aged mice. Nevertheless, alteration of the thyroid hormone signalling pathway may be a limiting factor, which impedes retinoic acid (RA) from exerting its modulating effect. Mild hypothyroidism is often described in the elderly. Thus, in the present study, it was of interest to determine if RA exerts its neurological modulating effect in mild hypothyroidism. To obtain further insight into this question, mice were submitted to a low propylthiouracyl (PTU) drink (0.05%) in order to slightly reduce the serum level of triiodothyronine (T3). A quantitative evaluation of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and of neurogranin (RC3, a RA target gene which codes for a protein considered as a good marker of synaptic plasticity) in PTU treated mice injected with vehicle or RA or T3 was carried out. The PTU-related decrease in expression of RAR, RXR and RC3 was restored following RA or T3 administration, as observed in aged mice. The amount of TR mRNA, which was not affected in PTU treated mice, was increased only after T3 treatment as observed in overt hypothyroidism. These results suggest that neurobiological alterations observed in aged mice are probably related to RA and T3 signalling pathway modifications associated, in part, with mild changes in thyroid function.

  10. Low-level laser therapy promotes dendrite growth via upregulating brain-derived neurotrophic factor expression

    Science.gov (United States)

    Meng, Chengbo; He, Zhiyong; Xing, Da

    2014-09-01

    Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via the increase of both BDNF mRNA and protein expression. In addition, dendrite growth was improved after LLLT, characterized by upregulation of PSD95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT can ameliorate Aβ-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Aβ-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of Alzheimer's disease.

  11. Hippocampal neurogenesis levels predict WATERMAZE search strategies in the aging brain.

    Directory of Open Access Journals (Sweden)

    Joana Gil-Mohapel

    Full Text Available The hippocampus plays a crucial role in the formation of spatial memories, and it is thought that adult hippocampal neurogenesis may participate in this form of learning. To better elucidate the relationship between neurogenesis and spatial learning, we examined both across the entire life span of mice. We found that cell proliferation, neuronal differentiation, and neurogenesis significantly decrease with age, and that there is an abrupt reduction in these processes early on, between 1.5-3 months of age. After this, the neurogenic capacity continues to decline steadily. The initial abrupt decline in adult neurogenesis was paralleled by a significant reduction in Morris Water Maze performance, however overall learning and memory remained constant thereafter. Further analysis of the search strategies employed revealed that reductions in neurogenesis in the aging brain were strongly correlated with the adoption of spatially imprecise search strategies. Overall, performance measures of learning and memory in the Morris Water Maze were maintained at relatively constant levels in aging animals due to an increase in the use of spatially imprecise search strategies.

  12. (-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

    Science.gov (United States)

    Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

    2016-09-01

    A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

  13. Synthesis of Se-75 labeled catecholamine derivatives: adrenal medulla tumor specific radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Basmadjian, G.P.; Sadek, S.; Ice, R.D. (Oklahoma Univ., Oklahoma City (USA). Health Sciences Center)

    Three classes of /sup 75/Se-labelled catecholamines have been synthesised. In class I the /sup 75/Se replaces the amine function of dopamine, using Na/sup 75/SeH. In class II the selenomethyl group replaces the -OH function in epinephrine. In class III /sup 75/Se replaces the ..beta..-carbon in catecholamine. NMR and mass spectroscopy were used to characterise the compounds.

  14. Arecoline inhibits catecholamine release from perfused rat adrenal gland

    Institute of Scientific and Technical Information of China (English)

    Dong-yoon LIM; Il-sik KIM

    2006-01-01

    Aim: To study the effect of arecoline, an alkaloid isolated from Areca catechu, on the secretion of catecholamines (CA) evoked by cholinergic agonists and the membrane depolarizer from isolated perfused rat adrenal gland. Methods: Adrenal glands were isolated from male Sprague-Dawley rats. The adrenal glands were perfused with Krebs bicarbonate solution by means of a peristaltic pump. The CA content of the perfusate was measured directly using the fluorometric method.Results: Arecoline (0.1-1.0 mmol/L) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by acetylcholine (ACh) (5.32 mmol/L), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP) (100 μmol/L for 2 min) and 3-(m-choloro-phenyl-carbamoyl-oxy)-2-butynyl trimethyl ammonium chloride (McN-A-343) (100 μmol/L for 2 min). However, lower doses of arecoline did not affect CA secretion of high K+ (56 mmol/L); higher doses greatly reduced CA secretion of high K+. Arecoline also failed to affect basal catecholamine output. Furthermore, in adrenal glands loaded with arecoline (0.3 mmol/L), CA secretory response evoked by Bay-K-8644 (10 μmol/L), an activator of L-type Ca2+ channels, was markedly inhibited, whereas CA secretion by cyclopiazonic acid (10 μmol/L), an inhibitor of cytoplasmic Ca2+-ATPase, was not affected. Nicotine (30 μmol/L), which was peffused into the adrenal gland for 60min, however, initially enhanced ACh-evoked CA secretory responses. As time elapsed, these responses became more inhibited, whereas the initially enhanced high K+-evoked CA release diminished. CA secretion evoked by DMPP and McNA-343 was significantly depressed in the presence of nicotine. Conclusion:Arecoline dose-dependently inhibits CA secretion from isolated perfused rat adrenal gland evoked by activation of cholinergic receptors. At lower doses arecoline does not inhibit CA secretion through membrane depolarization, but at larger doses it does. This inhibitory

  15. Level of serum neuron-specific enolase and brain damage in children with febrile seizures

    Institute of Scientific and Technical Information of China (English)

    Lang Chen; Qiaobin Chen; Fang Yang; Zhi Lin; Xinfu Lin; Ying Huang; Xin Zheng; Yu Lin

    2006-01-01

    final analysis without any loss. Levels of S-NSE were (5.17±1.31) μg/L in SFS group, (5.84±1.62) μg/L in CFS group and (4.98±1.51) μg/L in control group, respectively. There were no significant differences among groups (t =0.498- 1.727, P> 0.05).CONCLUSION: FS may be not able to cause a severe brain damage.

  16. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  17. Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

    Science.gov (United States)

    Arbour, Richard B

    2013-01-01

    Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological

  18. Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin.

    Science.gov (United States)

    Al-Asmari, Abdulrahman K; Ullah, Zabih; Al Masoudi, Aqeel Salman; Ahmad, Ishtiaque

    2017-01-01

    Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first-choice drug for the treatment of depression and anxiety. A recent report suggests that selective serotonin reuptake inhibitors can interact with the cytochrome P450 3A4 substrate, and another one suggests that STT enhances the antidepressant activity of FLX. However, the data are inconclusive. The present study was designed to explore the pharmacokinetic and pharmacodynamic consequences of coadministration of STT and FLX in experimental animals. For this, Wistar rats weighing 250±10 g were divided into four groups, including control, STT (40 mg/kg/day), FLX (20 mg/kg/day), and STT+FLX group, respectively. After the dosing period of 4 weeks, the animals were sacrificed, and the blood and brain samples were collected for the analysis of STT, simvastatin acid (STA), FLX, total cholesterol, triglyceride, high-density lipoprotein (HDL), 5-hydroxytryptamine, dopamine, and hydroxy indole acetic acid. It was found that the coadministration resulted in a significant increase in the bioavailability of STT in the plasma (41.8%) and brain (68.7%) compared to administration of STT alone (pSTT was also found to be increased significantly in the plasma and brain compared to that achieved after monotherapy (pSTT failed to improve the pharmacokinetics of FLX up to a significant level. The results of this study showed that the combined regimen significantly reduced the level of cholesterol and triglyceride and increased the level of HDL when compared to STT monotherapy. Furthermore, the coadministration of STT with FLX led to an elevated level of neurotransmitters in the brain (pSTT in the plasma and brain. The coadministration of these drugs also led to an improved lipid profile. However, in the long-term, this interaction may have a vital clinical importance because the increase in STT level may lead to life-threatening side

  19. Brain glucose metabolism is associated with hormone level in Cushing's disease: A voxel-based study using FDG-PET

    OpenAIRE

    Shuai Liu; Yinyan Wang; Kaibin Xu; Fan Ping; Renzhi Wang; Fang Li; Xin Cheng

    2016-01-01

    Chronic exposure to elevated levels of glucocorticoids can exert a neurotoxic effect in patients, possibly manifesting as molecular imaging alterations in patients. The aim of this study was to investigate the potential association between brain metabolism and elevated hormone level using 18F-fluorodeoxyglucose positron emission tomography. We retrospectively enrolled 92 consecutive patients with confirmed diagnosis of Cushing's disease. A voxel-based analysis was performed to investigate the...

  20. The alteration of plasma TGF-β1 levels in patients with brain tumors after tumor removal

    Directory of Open Access Journals (Sweden)

    Joon-Khim Loh

    2012-06-01

    Full Text Available Transforming growth factor (TGF β1 may be a candidate for a serologic tumor marker. In this study, the plasma levels of TGF-β1 in patients with brain tumors were measured using enzyme-linked immunosorbent assay before and after tumor removal. Patients were divided into four groups, the control group and the benign, malignant, and metastatic brain tumor groups. All brain tumor groups showed significant increases in the levels of TGF-β1 before tumor removal (6.36 ± 3.94, 17.0 ± 9.7, and 12.2 ± 10.3 ng/ml for the benign, malignant, and metastatic groups, respectively. When compared with the results obtained in the control group (1.12 ± 0.74 ng/ml, significant decreases in TGF-β1 concentrations after total tumor removal were found in both the benign and malignant brain tumor groups (2.55 ± 2.00 and 8.93 ± 5.73 ng/ml, respectively; p = 0.0001 and p = 0.003, respectively. On the other hand, plasma TGF-β1 levels in the metastatic brain tumor group showed a slight but significant increase (14.7 ± 9.3 ng/ml, p = 0.035 after tumor removal. In a case of low-grade astrocytoma, plasma levels of TGF-β1 were found to be 3.6 and 1.1 ng/ml before and after tumor removal, respectively. However, recurrent tumor was noted in this patient 7 months later, and the levels of TGF-β1 were 26.2 and 8.4 ng/ml before and after the second operation, respectively. The data show that plasma TGF-β1 was elevated in the circulation of patients with brain tumors and that significant decreases in TGF-β1 levels were observed after the removal of benign and malignant tumors. The results also suggest that TGF-β1 may be a useful serologic marker for brain tumors.

  1. Effects of aerobic exercise training on peripheral brain-derived neurotrophic factor and eotaxin-1 levels in obese young men.

    Science.gov (United States)

    Cho, Su Youn; Roh, Hee Tae

    2016-04-01

    [Purpose] The aim of the present study was to investigate the effects of aerobic exercise training on the levels of peripheral brain-derived neurotrophic factor and eotaxin-1 in obese young men. [Subjects and Methods] The subjects included sixteen obese young men with a body mass index greater than 25 kg/m(2). They were randomly divided between control and exercise groups (n = 8 in each group). The exercise group performed treadmill exercise for 40 min, 3 times a week for 8 weeks at the intensity of 70% heart rate reserve. Blood collection was performed to examine the levels of serum glucose, plasma malonaldehyde, serum brain-derived neurotrophic factor, and plasma eotaxin-1 before and after the intervention (aerobic exercise training). [Results] Following the intervention, serum BDNF levels were significantly higher, while serum glucose, plasma MDA, and plasma eotaxin-1 levels were significantly lower than those prior to the intervention in the exercise group. [Conclusion] Aerobic exercise training can induce neurogenesis in obese individuals by increasing the levels of brain-derived neurotrophic factor and reducing the levels of eotaxin-1. Alleviation of oxidative stress is possibly responsible for such changes.

  2. Interaction between different sports branches such as taekwondo, box, athletes and serum brain derived neurotrophic factor levels.

    Science.gov (United States)

    Oztasyonar, Yunus

    2017-04-01

    This study aimed to compare serum brain-derived neurotrophic factor (BDNF) levels "which contributes in both neuron development/regeneration" between combat sport braches, which requires high attention and concentration and can lead micro and macro brain trauma, and athleticism, which requires durability in competition. The study design included 4 groups. Group 1 had sedentary participants, and group 2 athletes (middle and long runners) who exercised for two 2-hour daily training sessions 6 days a week. group 3 included boxers, and group 4 taekwondo fighters. We investigated changes in the blood BDNF levels of taekwondo fighters, boxers, and athletes before and after training and compared them among each other and with measurements of sedentary controls. All athletes had higher basal BDNF levels than sedentary participants. Boxers and taekwondo athletes had especially high basal BDNF levels. When we compared different sports branch each other Pre- and post- training BDNF values are ranked as follows: taekwondo > boxing > athletes > sedentary. In sport branches such as combat sports and athletes, serum BDNF levels have been demonstrated to be higher after training than before. In addition, serum BDNF levels were higher in taekwondo fighters and boxers than athletes. BDNF might have a role in the protection mechanism against brain damage or contributes in occurrence and maintenance of high attention and concentration especially among combat sports.

  3. Effects of cell phone radiation on lipid peroxidation, glutathione and nitric oxide levels in mouse brain during epileptic seizure.

    Science.gov (United States)

    Esmekaya, Meric Arda; Tuysuz, Mehmet Zahid; Tomruk, Arın; Canseven, Ayse G; Yücel, Engin; Aktuna, Zuhal; Keskil, Semih; Seyhan, Nesrin

    2016-09-01

    The objective of the this study was to evaluate the effects of cellular phone radiation on oxidative stress parameters and oxide levels in mouse brain during pentylenetetrazole (PTZ) induced epileptic seizure. Eight weeks old mice were used in the study. Animals were distributed in the following groups: Group I: Control group treated with PTZ, Group II: 15min cellular phone radiation+PTZ treatment+30min cellular phone radiation, Group III: 30min cellular phone radiation+PTZ treatment+30min cellular phone radiation. The RF radiation was produced by a 900MHz cellular phone. Lipid peroxidation, which is the indicator of oxidative stress was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARS). The glutathione (GSH) levels were determined by the Ellman method. Tissue total nitric oxide (NOx) levels were obtained using the Griess assay. Lipid peroxidation and NOx levels of brain tissue increased significantly in group II and III compared to group I. On the contrary, GSH levels were significantly lower in group II and III than group I. However, no statistically significant alterations in any of the endpoints were noted between group II and Group III. Overall, the experimental findings demonstrated that cellular phone radiation may increase the oxidative damage and NOx level during epileptic activity in mouse brain.

  4. Predicting Successful Pulmonary Vein Isolation In Patients With Atrial Fibrillation By Brain Natriuretic Peptide Plasma Levels

    Directory of Open Access Journals (Sweden)

    Dong-In Shin

    2009-09-01

    Full Text Available Background: Catheter ablation for atrial fibrillation is a clinically established treatment by now while success rate varies between 60% and 85%. Interventional treatment of atrial fibrillation is still a challenging technique associated with a long procedure time and risk of major complications in up to 6 % of treated patients. The aim of this study was to investigate the predictive value of plasma brain natriuretic peptide (BNP in patients undergoing pulmonary vein isolation concerning stable sinus rhythm after ablation.Methods: In 68 consecutive patients with atrial fibrillation (AF and normal left ventricular ejection fraction, BNP was measured at baseline before pulmonary vein isolation (PVI. All patients received a 7-days-holter monitoring 3 months after radiofrequency (RF ablation in order to detect recurrent AF episodes. Results: 48 patients with paroxysmal and 20 patients with persistent AF were enrolled. Baseline BNP was significantly higher in patients with persistent AF compared to patients with paroxysmal AF (145,5 pg/ml vs. 84,4 pg/ml; p<0,05. 3 months after PVI 38 patients (79,1% with paroxysmal AF had a stable sinus rhythm documented on 7-days-holter monitoring, where as in 10 patients (20,9% AF episodes were detected. Patients with a successful PVI showed significantly lower BNP plasma levels at baseline compared to patients with AF recurrrence (68,7 pg/ml vs. 144,1 pg/ml; p<0,05. In patients with persistent AF 55% (11 cases had no recurrence of AF at 3 months 7-days holter and in 9 patients (45% AF recurred. BNP plasma levels at baseline were lower in patients with stable sinusrhythm after 3 months compared to the group of recurrent AF (105,8 pg/ml vs. 193,3 pg/ml; p=0,11. Conclusion: Patients with AF and low preprocedural BNP plasma levels showed a better outcome after PVI. Thus BNP may be helpful in patient selection for a successful treatment of AF by PVI.

  5. GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens.

    Science.gov (United States)

    Lymperopoulos, Anastasios; Brill, Ava; McCrink, Katie A

    2016-08-01

    The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which release NE on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release Epi (mainly) and NE. All of the Epi in the body and a significant amount of circulating NE derive from the adrenal medulla. The secretion of CAs from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors, the vast majority of which are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as "presynaptic autoreceptors" in this regard. There is a plethora of CA-secretagogue signals acting on these receptors but some of them, most notably the α2ARs, inhibit CA secretion. Over the past few years, however, a few new proteins present in chromaffin cells have been uncovered to participate in CA secretion regulation. Most prominent among these are GRK2 and β-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function. The present review will discuss the molecular and signaling mechanisms by which adrenal chromaffin cell-residing GPCRs and their regulatory proteins modulate CA synthesis and secretion. Particular emphasis will be given to the newly discovered roles of GRK2 and β-arrestins in these processes and particular points of focus for future research will be highlighted, as well.

  6. Catalytic domain surface residues mediating catecholamine inhibition in tyrosine hydroxylase.

    Science.gov (United States)

    Briggs, Gabrielle D; Bulley, Jesse; Dickson, Phillip W

    2014-03-01

    Tyrosine hydroxylase (TH) performs the rate-limiting step in catecholamine (CA) synthesis and is a tetramer composed of regulatory, catalytic and tetramerization domains. CAs inhibit TH by binding two sites in the active site; one with high affinity and one with low affinity. Only high affinity CA binding requires the regulatory domain, believed to interact with the catalytic domain in the presence of CA. Without a crystal structure of the regulatory domain, the specific areas involved in this process are largely undefined. It is not clear whether the regulatory domain-catalytic domain interaction is asymmetrical across the tetramer to produce the high and low affinity sites. To investigate this, pure dimeric TH was generated through double substitution of residues at the tetramerization interface and dimerization salt bridge (K170E/L480A). This was shown to be the core regulatory unit of TH for CA inhibition, possessing both high and low affinity CA binding sites, indicating that there is symmetry between dimers of the tetramer. We also examined possible regulatory domain-interacting regions on the catalytic domain that mediate high affinity CA binding. Using site-directed mutagenesis, A297, E362/E365 and S368 were shown to mediate high affinity dopamine inhibition through V(max) reduction and increasing the K(M) for the cofactor.

  7. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis

    Science.gov (United States)

    Nguyen, Khoa D.; Qiu, Yifu; Cui, Xiaojin; Goh, Y.P. Sharon; Mwangi, Julia; David, Tovo; Mukundan, Lata; Brombacher, Frank; Locksley, Richard M.; Chawla, Ajay

    2011-01-01

    All homeotherms utilize thermogenesis to maintain core body temperature, ensuring that cellular functions and physiologic processes can ensue in cold environments1-3. In the prevailing model, when the hypothalamus senses cold temperatures, it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue (BAT) and white adipose tissue (WAT)4,5. Acting via the β3-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes6, whereas it stimulates the expression of thermogenic genes, such as PPARγ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1), and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes7-9. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report an unexpected requirement for the interleukin 4 (IL4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Cold exposure rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in BAT and lipolysis in WAT. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL4 increased thermogenic gene expression, fatty acid mobilization, and energy expenditure, all in a macrophage-dependent manner. We have thus discovered a surprising role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold. PMID:22101429

  8. Altered catecholamine receptor affinity in rabbit aortic intimal hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    O' Malley, M.K.; Cotecchia, S.; Hagen, P.O. (Duke University Medical Center, Durham, NC (USA))

    1991-08-01

    Intimal thickening is a universal response to endothelial denudation and is also thought to be a precursor of atherosclerosis. The authors have demonstrated selective supersensitivity in arterial intimal hyperplasia to norepinephrine and they now report a possible mechanism for this. Binding studies in rabbit aorta with the selective alpha 1-adrenergic radioligand 125I-HEAT demonstrated that there was no change in receptor density (20 {plus minus} 4 fmole/10(6) cells) in intact vascular smooth muscle cells at either 5 or 14 days after denudation. However, competition studies showed a 2.6-fold increase in alpha 1-adrenergic receptor affinity for norepinephrine in intimal hyperplastic tissue (P less than 0.05). This increased affinity for norepinephrine was associated with a greater increase in 32P-labeled phosphatidylinositol (148% intimal thickening versus 76% control) and phosphatidic acid (151% intimal thickening versus 56% control) following norepinephrine stimulation of free floating rings of intimal hyperplastic aorta. These data suggest that the catecholamine supersensitivity in rabbit aortic intimal hyperplasia is receptor mediated and may be linked to the phosphatidylinositol cycle.

  9. Lack of beta-adrenergic role for catecholamines in the development of hyperglycemia and ketonaemia following acute insulin withdrawal in type I diabetic patients.

    Science.gov (United States)

    Beylot, M; Sautot, G; Dechaud, H; Cohen, R; Riou, J P; Serusclat, P; Mornex, R

    1985-04-01

    In order to evaluate the role of beta-receptor mediated effects of catecholamines in the metabolic deterioration following insulin withdrawal in insulin-dependent diabetic patients we have measured in 5 patients metabolic substrate and hormone concentrations during a 6 hours arrest of insulin infusion, without or with a simultaneous infusion of propranolol. During insulin deprivation plasma epinephrine and norepinephrine increased slightly (from 107 +/- 10 ng/L to 173 +/- 6 ng/L and from 307 +/- 37 ng/L to 518 +/- 77/ng/L respectively (p less than 0.05), cortisol decreased physiologically, but growth hormone and glucagon were not significantly modified. Free insulin decreased progressively from 12.2 +/- 2.5 mU/L to 5.4 +/- 1.1 mU/L (p less than 0.01). Blood glucose and ketone bodies rose sharply before any significant change in catecholamine levels. Plasma free fatty acids and blood glycerol increased progressively and their rise appeared somewhat temporally related to the variations of catecholamine levels. The addition of propranolol to insulin deprivation did not modify the changes in hormone concentrations in spite of a slightly greater rise of epinephrine (from 78 +/- 4 ng/L to 179 +/- 7 ng/L, p less than 0.05) and norepinephrine (from 395 +/- 80 ng/L to 679 +/- 153 ng/L, p less than 0.05). The rises of glucose and ketone bodies were unaffected whereas the increases of free fatty acids and glycerol were slightly blunted. In conclusion, we have no evidence for a beta-adrenergic mediated role for catecholamines in the development of hyperglycaemia and ketonaemia in non-stressed insulin deprived diabetic patients, and only small evidence for a permissive effect on lipolysis.

  10. Hierarchical random cellular neural networks for system-level brain-like signal processing.

    Science.gov (United States)

    Kozma, Robert; Puljic, Marko

    2013-09-01

    Sensory information processing and cognition in brains are modeled using dynamic systems theory. The brain's dynamic state is described by a trajectory evolving in a high-dimensional state space. We introduce a hierarchy of random cellular automata as the mathematical tools to describe the spatio-temporal dynamics of the cortex. The corresponding brain model is called neuropercolation which has distinct advantages compared to traditional models using differential equations, especially in describing spatio-temporal discontinuities in the form of phase transitions. Phase transitions demarcate singularities in brain operations at critical conditions, which are viewed as hallmarks of higher cognition and awareness experience. The introduced Monte-Carlo simulations obtained by parallel computing point to the importance of computer implementations using very large-scale integration (VLSI) and analog platforms.

  11. Effects of Wen Dan Tang on insomnia-related anxiety and levels of the brain-gut peptide Ghrelin

    Institute of Scientific and Technical Information of China (English)

    Liye Wang; Binghe Guan; Xiaolan Liu; Yuehan Song; Feng Li; Yan Liu; Jie Ma; Meng Mao; Fengzhi Wu; Ying Wu; Sinai Li

    2014-01-01

    Ghrelin, a brain-gut peptide that induces anxiety and other abnormal emotions, contributes to the effects of insomnia on emotional behavior. In contrast, the traditional Chinese Medi-cine remedy Wen Dan Tang reduces insomnia-related anxiety, which may perhaps correspond to changes in the brain-gut axis. This suggests a possible relationship between Wen Dan Tang’s pharmacological mechanism and the brain-gut axis. Based on this hypothesis, a sleep-deprived rat model was induced and Wen Dan Tang was administered using oral gavage during model es-tablishment. Wen Dan Tang signiifcantly reduced insomnia-related anxiety and prevented Ghrelin level decreases following sleep deprivation, especially in the hypothalamus. Increased expression of Ghrelin receptor mRNA in the hypothalamus was also observed, suggesting that reduced anxi-ety may be a result of Wen Dan Tang’s regulation of Ghrelin-Ghrelin receptors.

  12. Brain and gonadal aromatase activity and steroid hormone levels in female and polymorphic males of the peacock blenny Salaria pavo.

    Science.gov (United States)

    Gonçalves, David; Teles, Magda; Alpedrinha, João; Oliveira, Rui F

    2008-11-01

    In the peacock blenny Salaria pavo large males with well-developed secondary sexual characters establish nests and attract females while small "sneaker" males mimic female sexual displays in order to approach the nests of larger males and parasitically fertilize eggs. These alternative reproductive tactics are sequential, as sneakers irreversibly switch into nesting males. This transition involves major morphologic and behavioral changes and is likely to be mediated by hormones. This study focuses on the role of aromatase, an enzyme that catalyses the conversion of androgens into estrogens, in the regulation of male sexual polymorphism in S. pavo. For this, sex steroid plasma levels and aromatase activity (AA) in gonads, whole brain and brain macroareas were determined in sneakers, transitional males (i.e. sneakers undergoing the transition into nesting males), nesting males and females collected in the field. AA was much higher in ovarian tissue than in testicular tissue and accordingly circulating estradiol levels were highest in females. This supports the view that elevated AA and estradiol levels are associated with the development of a functional ovary. Transitional males are in a non-reproductive phase and had underdeveloped testes when compared with sneakers and nesting males. Testicular AA was approximately 10 times higher in transitional males when compared with sneakers and nesting males, suggesting high AA has a suppressive effect on testicular development. Nesting males had significantly higher plasma levels of both testosterone (T) and 11-ketotestosterone when compared with the other male morphs and previous studies demonstrated that these androgens suppress female-like displays in sneakers. In the brain, AA was highest in macroareas presumably containing hypothalamic nuclei traditionally associated with the regulation of reproductive behaviors. Overall, females presented the highest levels of brain AA. In male morphs AA increased from sneakers, to

  13. X-ray micro-tomography for investigations of brain tissues on cellular level

    Science.gov (United States)

    Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Zanette, Irene; Zdora, Marie-Christine; Bikis, Christos; Hipp, Alexander; Hieber, Simone E.; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

    2016-10-01

    X-ray imaging in absorption contrast mode is well established for hard tissue visualization. However, performance for lower density materials is limited due to a reduced contrast. Our aim is three-dimensional (3D) characterization of micro-morphology of human brain tissues down to (sub-)cellular resolution within a laboratory environment. Using the laboratory-based microtomography (μCT) system nanotom m (GE Sensing and Inspection Technologies GmbH, Wunstorf, Germany) and synchrotron radiation at the Diamond-Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK), we have acquired 3D data with a resolution down to 0.45 μm for visualization of a human cerebellum specimen down to cellular level. We have shown that all selected modalities, namely laboratory-based absorption contrast micro-tomography (LBμCT), synchrotron radiation based in-line single distance phase contrast tomography (SDPR) and synchrotron radiation based single-grating interferometry (GI), can reach cellular resolution for tissue samples with a size in the mm-range. The results are discussed qualitatively in comparison to optical microscopy of haematoxylin and eosin (HE) stained sections. As phase contrast yields to a better data quality for soft tissues and in order to overcome restrictions of limited beamline access for phase contrast measurements, we have equipped the μCT system nanotom m with a double-grating phase contrast set-up. Preliminary experimental results of a knee sample consisting of a bony part and a cartilage demonstrate that phase contrast data exhibits better quality compared to absorption contrast. Currently, the set-up is under adjustment. It is expected that cellular resolution would also be achieved. The questions arise (1) what would be the quality gain of laboratory-based phase contrast in comparison to laboratory-based absorption contrast tomography and (2) could laboratory-based phase contrast data provide comparable results to synchrotron radiation based

  14. Vanillylmandelic acid, homovanillic acid, and catecholamines in urine of infants with neuroblastoma 6- to 11-month-old.

    Science.gov (United States)

    Nishi, M; Miyake, H; Takeda, T; Takasugi, N; Sato, Y; Hanai, J

    1986-12-01

    The amounts of vanillylmandelic acid (VMA), homovanillic acid (HVA), and catecholamines (adrenaline, noradrenaline, and dopamine) in 24-hr urine specimens of 10 infants with neuroblastoma detected through mass screening in Sapporo City (patient group) were compared with those of 24 healthy infants (control group). The ages of the infants of both groups ranged from 6 to 11 months, which agrees with the age when mass screening is performed. For VMA and HVA, the mean value plus two or three times the standard deviation of the control group clearly separated the two groups in the units of mg/day, microgram/mg of creatinine, mg/kg/day, and mg/m2/day. The cut off values of 24 micrograms/mg of creatinine for VMA and 25 micrograms/mg of creatinine for HVA are now being used by us for assaying 24-hr urine specimens. No significant difference was found between the groups in levels of catecholamines, but their data were thought to be useful as normal values, since few published data regarding their normal values are available.

  15. Validated LC-MS/MS method for simultaneous quantification of resveratrol levels in mouse plasma and brain and its application to pharmacokinetic and brain distribution studies.

    Science.gov (United States)

    Ramalingam, Prakash; Ko, Young Tag

    2016-02-01

    A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine resveratrol levels in plasma and brain tissue in mice for supporting pharmacokinetic and brain distribution studies. Analytes were separated using a Sepax BR-C18 analytical column (5μm, 120Å, 1.0×100mm) and eluted using an isocratic elution mobile phase acetonitrile and 0.01% formic acid [60:40, v/v] at a flow rate of 0.1mL/min. Precursor and product ion transitions for analyte resveratrol m/z 226.9>184.8 and curcumin m/z 367.1>148.9 were monitored using triple quadrupole mass spectrometer with multiple reaction monitoring (MRM) in negative ionization mode. The method was validated with respect to accuracy, within- and between-day precision, linearity, limit of quantification, recovery, and matrix effects of analyte. The inter- and intra-day accuracy and precision were within the range of the US Food and Drug Administration (FDA) acceptance criteria, for both matrices. The method was also successfully applied to pharmacokinetic and brain distribution studies of resveratrol after intravenous administration of free resveratrol and resveratrol-loaded solid lipid nanoparticles to mice. The combined use of serial blood sampling, small sample volume, simple extraction, and capillary depletion method drastically improved resveratrol analysis from biological matrices.

  16. Evolution of brain-derived neurotrophic factor levels after autologous hematopietic stem cell transplantation in multiple sclerosis.

    Science.gov (United States)

    Blanco, Y; Saiz, A; Costa, M; Torres-Peraza, J F; Carreras, E; Alberch, J; Jaraquemada, D; Graus, F

    A neuroprotective role of inflammation has been suggested based on that immune cells are the main source of brain-derived neurotrophic factor (BDNF). We investigated the 3-year evolution of BDNF levels in serum, CSF and culture supernatant of peripheral blood mononuclear cells (PBMC), unstimulated and stimulated with anti-CD3 and soluble anti-CD28 antibodies, in 14 multiple sclerosis patients who underwent an autologous hematopoietic stem cell transplantation (AHSCT). BDNF levels were correlated with previously reported MRI measures that showed a reduction of T2 lesion load and increased brain atrophy, mainly at first year post-transplant. A significant decrease of serum BDNF levels was seen at 12 months post-transplant. BDNF values were found significantly lower in stimulated but not in unstimulated PBMC supernatants during the follow-up, supporting that AHSCT may induce a down-regulation of BDNF production. The only significant correlation was found between CSF BDNF levels and T2 lesion load before and 1 year after AHSCT, suggesting that BDNF reflects the past and ongoing inflammatory activity and demyelination of these highly active patients. Our study suggests that AHSCT can reduce BDNF levels to values associated with lower activity. This decrease does not seem to correlate with the brain atrophy measures observed in the MRI.

  17. Catecholamine effects on lipolysis and blood flow in human abdominal and femoral adipose tissue.

    Science.gov (United States)

    Millet, L; Barbe, P; Lafontan, M; Berlan, M; Galitzky, J

    1998-07-01

    With the use of the microdialysis method, the present study, performed on young, healthy, nonobese subjects of both genders, compares the effects of locally infused catecholamines on glycerol concentration and blood flow in abdominal (Abd) and femoral (Fem) adipose tissue. Physiological activation of the sympathetic nervous system through active tilt was also investigated. In both genders, extracellular glycerol concentration was higher in Fem than in Abd adipose tissue. Local blood flow was lower in Fem than in Abd adipose tissue. Isoproterenol perfusion increased extracellular glycerol levels, but no differences were found by gender or fat-deposit site. Isoproterenol induced a greater increase in local blood flow in Fem adipose tissue in both genders. Epinephrine and norepinephrine perfusion increased extracellular glycerol and reduced blood flow. No major differences were found according to gender and fat-deposit site. Active tilt increased plasma glycerol, free fatty acid, norepinephrine levels, and extracellular glycerol concentration to the same extent whatever the gender and fat deposit. Thus, Fem adipose tissue is characterized by a higher extracellular glycerol concentration and a lower blood flow than is Abd tissue in men and women. In these tissues, in situ lipolysis and local blood flow were similar in response to adrenergic stimulation.

  18. Plasma prolactin, renin and catecholamines in young normotensive and borderline hypertensive subjects.

    Science.gov (United States)

    Saito, I; Takeshita, E; Saruta, T; Nagano, S; Sekihara, T

    1984-02-01

    It has been reported that patients with essential hypertension have high plasma prolactin levels and suggested that reduced central dopaminergic activity may be a factor in the pathogenesis of essential hypertension. This study examines the influence of posture on plasma prolactin, plasma catecholamines, plasma renin activity, blood pressure and heart rate in 24 patients with borderline hypertension (age 19 +/- 1 years) and 20 normotensive subjects matched for age and body mass index. Supine plasma prolactin levels were similar in both groups [borderline hypertension, 11.3 +/- 0.7 ng/ml; normotensive, 10.7 +/- 0.8 ng/ml (mean +/- s.e.m.)] and no increase in plasma prolactin was observed after 10 min standing in both groups. Normotensive and borderline hypertensive subjects had similar values for supine and upright plasma renin activity and plasma norepinephrine. There were no significant correlations between supine plasma prolactin and supine blood pressure, supine plasma renin activity or plasma norepinephrine when data from both normotensive and borderline hypertensive subjects were combined. These results may provide indirect evidence against the occurrence of reduced central dopaminergic activity in borderline hypertension.

  19. Basal brain oxidative and nitrative stress levels are finely regulated by the interplay between superoxide dismutase 2 and p53.

    Science.gov (United States)

    Barone, Eugenio; Cenini, Giovanna; Di Domenico, Fabio; Noel, Teresa; Wang, Chi; Perluigi, Marzia; St Clair, Daret K; Butterfield, D Allan

    2015-11-01

    Superoxide dismutases (SODs) are the primary reactive oxygen species (ROS)-scavenging enzymes of the cell and catalyze the dismutation of superoxide radicals O2- to H2O2 and molecular oxygen (O2). Among the three forms of SOD identified, manganese-containing SOD (MnSOD, SOD2) is a homotetramer located wholly in the mitochondrial matrix. Because of the SOD2 strategic location, it represents the first mechanism of defense against the augmentation of ROS/reactive nitrogen species levels in the mitochondria for preventing further damage. This study seeks to understand the effects that the partial lack (SOD2(-/+) ) or the overexpression (TgSOD2) of MnSOD produces on oxidative/nitrative stress basal levels in different brain isolated cellular fractions (i.e., mitochondrial, nuclear, cytosolic) as well as in the whole-brain homogenate. Furthermore, because of the known interaction between SOD2 and p53 protein, this study seeks to clarify the impact that the double mutation has on oxidative/nitrative stress levels in the brain of mice carrying the double mutation (p53(-/-) × SOD2(-/+) and p53(-/-) × TgSOD2). We show that each mutation affects mitochondrial, nuclear, and cytosolic oxidative/nitrative stress basal levels differently, but, overall, no change or reduction of oxidative/nitrative stress levels was found in the whole-brain homogenate. The analysis of well-known antioxidant systems such as thioredoxin-1 and Nrf2/HO-1/BVR-A suggests their potential role in the maintenance of the cellular redox homeostasis in the presence of changes of SOD2 and/or p53 protein levels. © 2015 Wiley Periodicals, Inc.

  20. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia: A systematic review

    Science.gov (United States)

    Cui, Huiru; Jin, Yi; Wang, Jijun; Weng, Xuchu; Li, Chunbo

    2012-01-01

    Background There is increasing interest in the role of brain-derived neurotrophic factor (BDNF) in the onset and course of schizophrenia, but there are conflicting reports about serum levels of BDNF in patients with schizophrenia. Aim Conduct a meta-analysis combining studies from China and other countries that have evaluated the relationship of serum BDNF levels to schizophrenia. Method We used Cochrane methodology and RevMan 5.1 software to identify and pool the results of studies. Electronic searches of western and Chinese registries and follow-up assessment of references located 268 potential articles. Twenty-five articles (20 in English and 5 in Chinese) published before December 2011 that used case-control methods, included patients with schizophrenia who had no concurrent disorders, and used ELISA technology to assess serum BDNF were included in the analysis. The main outcome was the pooled standardized mean difference (SMD) between cases and controls. The quality of the studies was independently assessed by two raters using the GRADE system. The heterogeneity, sensitivity and potential publication bias of the studies was evaluated using RevMan. Results The pooled sample included 1663 patients with schizophrenia and 1355 controls. Fifteen of the included studies were rated as ‘poor quality’ and 10 were rated as ‘very poor quality’. The results of the studies were quite heterogenous (I2=95%) but subgroup analyses found that the heterogeneity was not related to country of origin, sample size, age, gender, prior use of antipsychotic medication, or study quality. The pooled SMD (computed using a random-effect model because of study heterogeneity) was -0.74 (95% CI, -0.99∼-0.50; Z=5.99, pbias. Conclusion Despite the robust statistical findings of lower serum BDNF in patients with schizophrenia than in controls, given the low quality of the available studies and the substantial heterogeneity between studies, the evidence of lower serum BDNF in patients

  1. Detection of Low Level Microwave Radiation Induced Deoxyribonucleic Acid Damage Vis-à-vis Genotoxicity in Brain of Fischer Rats

    Science.gov (United States)

    Deshmukh, Pravin Suryakantrao; Megha, Kanu; Banerjee, Basu Dev; Ahmed, Rafat Sultana; Chandna, Sudhir; Abegaonkar, Mahesh Pandurang; Tripathi, Ashok Kumar

    2013-01-01

    Background: Non-ionizing radiofrequency radiation has been increasingly used in industry, commerce, medicine and especially in mobile phone technology and has become a matter of serious concern in present time. Objective: The present study was designed to investigate the possible deoxyribonucleic acid (DNA) damaging effects of low-level microwave radiation in brain of Fischer rats. Materials and Methods: Experiments were performed on male Fischer rats exposed to microwave radiation for 30 days at three different frequencies: 900, 1800 and 2450 MHz. Animals were divided into 4 groups: Group I (Sham exposed): Animals not exposed to microwave radiation but kept under same conditions as that of other groups, Group II: Animals exposed to microwave radiation at frequency 900 MHz at specific absorption rate (SAR) 5.953 × 10−4 W/kg, Group III: Animals exposed to 1800 MHz at SAR 5.835 × 10−4 W/kg and Group IV: Animals exposed to 2450 MHz at SAR 6.672 × 10−4 W/kg. At the end of the exposure period animals were sacrificed immediately and DNA damage in brain tissue was assessed using alkaline comet assay. Results: In the present study, we demonstrated DNA damaging effects of low level microwave radiation in brain. Conclusion: We concluded that low SAR microwave radiation exposure at these frequencies may induce DNA strand breaks in brain tissue. PMID:23833433

  2. Protective effect of taurine on the decreased biogenic amine neurotransmitter levels in the brain of mice exposed to arsenic.

    Science.gov (United States)

    Liu, Xiaohui; Piao, Fengyuan; Li, Yachen

    2013-01-01

    Arsenic (As) exposure has a toxic effect on the central nervous system, especially on learning and memory. Norepinephrine (NE), dopamine (DA), and serotonin (5-HT) play an important role in learning and memory function of the brain. In the present study, the protective effect of taurine on the disturbed biogenic amine neurotransmitter levels in the mouse brain induced by arsenic was examined. Sixty SPF mice were divided into three groups. The As exposure group was administered with 4 ppm As(2)O(3) through drinking water for 60 days. The protective group was treated with both 4 ppm As(2)O(3) and 150 mg/kg taurine. The control group was given drinking water alone. The levels of NE, DA, and 5-HT were determined by HPLC in the cerebrum and cerebellum of mice. Ultrastructure of synapses in brain tissue of mice was observed in these groups by transmission electron microscopy. The mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH) as NE, DA, and 5-HT synzymes were also analyzed by real-time RT-PCR. The results showed that the concentrations of NE, DA, and 5-HT; the number of synaptic vesicles; and the expressions of TH, TPH, and DBH genes in the brains of mice exposed to As alone were significantly decreased. However, administration of taurine significantly alleviated the toxic effect on biochemicals detected in the experiment, compared with that in the brain of mice exposed to As alone. These results indicated that taurine was effective in counteracting the decreased biogenic amine neurotransmitter level and the mRNA expressions of their synzymes induced by arsenic.

  3. Catecholamine and volume therapy for cardiac surgery in Germany--results from a postal survey.

    Directory of Open Access Journals (Sweden)

    Christoph Sponholz

    Full Text Available Management of cardiac surgery patients is a very standardized procedure in respective local institutions. Yet only very limited evidence exists concerning optimal indication, safety and efficacy of hemodynamic monitoring catecholamine and fluid therapy.Between April and May 2013, all 81 German anaesthesia departments involved in cardiac surgery care were asked to participate in a questionnaire addressing the institutional specific current practice in hemodynamic monitoring, catecholamine and volume therapy.51 (63% questionnaires were completed and returned. All participating centers used basic hemodynamic monitoring (i.e. invasive arterial blood pressure and central venous pressure, supplemented by transesophageal echocardiography. Pulmonary arterial catheter and calibrated trend monitoring devices were also routinely available. In contrast, non-calibrated trend monitoring and esophageal doppler ultrasound devices were not commonly in use. Cerebral oximetry is increasingly emerging, but lacks clear indications. The majority of patients undergoing cardiac surgery, especially in university hospitals, required catecholamines during perioperative care, In case of low cardiac output syndrome, dobutamine (32%, epinephrine (30% or phosphodiesterase inhibitors (8% were first choice. In case of hypotension following vasoplegia, norepinephrine (96% represented the most common catecholamine. 88% of the participating centers reported regular use of colloid fluids, with hydroxyethyl starches (HES being first choice (64%.Choice of hemodynamic monitoring is homogenous throughout German centers treating cardiac surgery patients. Norepinephrine is the first line catecholamine in cases of decrease in peripheral vascular resistance. However, catecholamine choice for low cardiac output syndrome varies considerably. HES was the primary colloid used for fluid resuscitation. After conduct of this survey, HES use was restricted by European regulatory authorities in

  4. A Population Based Study of the Genetic Association between Catecholamine Gene Variants and Spontaneous Low-Frequency Fluctuations in Reaction Time.

    Directory of Open Access Journals (Sweden)

    Jojanneke A Bastiaansen

    Full Text Available The catecholamines dopamine and noradrenaline have been implicated in spontaneous low-frequency fluctuations in reaction time, which are associated with attention deficit hyperactivity disorder (ADHD and subclinical attentional problems. The molecular genetic substrates of these behavioral phenotypes, which reflect frequency ranges of intrinsic neuronal oscillations (Slow-4: 0.027-0.073 Hz; Slow-5: 0.010-0.027 Hz, have not yet been investigated. In this study, we performed regression analyses with an additive model to examine associations between low-frequency fluctuations in reaction time during a sustained attention task and genetic markers across 23 autosomal catecholamine genes in a large young adult population cohort (n = 964, which yielded greater than 80% power to detect a small effect size (f(2 = 0.02 and 100% power to detect a small/medium effect size (f(2 = 0.15. At significance levels corrected for multiple comparisons, none of the gene variants were associated with the magnitude of low-frequency fluctuations. Given the study's strong statistical power and dense coverage of the catecholamine genes, this either indicates that associations between low-frequency fluctuation measures and catecholamine gene variants are absent or that they are of very small effect size. Nominally significant associations were observed between variations in the alpha-2A adrenergic receptor gene (ADRA2A and the Slow-5 band. This is in line with previous reports of an association between ADRA2A gene variants and general reaction time variability during response selection tasks, but the specific association of these gene variants and low-frequency fluctuations requires further confirmation. Pharmacological challenge studies could in the future provide convergent evidence for the noradrenergic modulation of both general and time sensitive measures of intra-individual variability in reaction time.

  5. EFFECTS OF ALFENTANIL AND ESMOLOL ON HEMODYNAMIC AND CATECHOLAMINE RESPONSE TO TRACHEAL INTUBATION

    Institute of Scientific and Technical Information of China (English)

    龚志毅; 罗爱伦

    1999-01-01

    Objective. To compare the effects of alfentanil and esmolol on hemodynamic and catecholamine responsee to tracheal intubation.Mahods. Thirty-five adult patients were randomly allocated to one of three groups, Group A (control group), Group B (esmolol groap) and Group C (alfentanil group). The patients received either 2 mg/kg esmolol (in Group B) or 30μg/kg alfentanil (in Group C) before intulmtion. Tracheal intubation was performed with 4 mg/kg thiopental and 0. 1 mg/kg vecuronium and 3% isoflurane. Systolic blood pressure(SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), norepinephrine(NE),epinephrine(E) and dopamine (DA) were measured before and after intubtttion.Results.The control group had a baseline SBP of 149±23 mmHg while Groups B,C had a baseline SBP of 148±23,and 150±21mmHg,respectively(P>0.05),Three min after tracheal intubation,the control group SBP increased to 160±30mmHg and Group B remained at the baseline level ,147±5mmHg,and Goup C significantly decreased to 91±22mmHg(P<0.01).Two min after intubation HR in Group B increased significantly but 3 min after intubation HR in Groups B and C were significantly lower than that of control group(P<0.05).NE in Groups A and B increased significatly to 5.75±3.51 and 6.75±3.30nmol/L 3 min after intubation(P<0.01).In Group C,3min after intubation NE was not significantly different from the baseline but E becreased significantly(P<0.01).Conclusion.2mg/kg esmolol can moderate the hemodynamic response to tracheal intubation to a certain extent and 30μg/kg alfentanil can completely attenuate the hemodynamic and catecholamine responses.

  6. Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice

    Institute of Scientific and Technical Information of China (English)

    Abrar M Tamboli; Rukhsana A Rub; Pinaki Ghosh; SL Bodhankar

    2012-01-01

    Objective:To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid (GABA) in brain of mice in Pentylenetetrazol (PTZ) seizure models. Methods:The anticonvulsant activity of the isolated lobeline (5, 10, 20 and 30 mg/kg, i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lobeline on brain GABA level in seizures induced by PTZ. Diazepam was used as reference anticonvulsant drugs for comparison. Results:Isolated lobeline (10, 20 and 30 mg/kg, i.p.) significantly delayed and antagonized (P<0.050–0.001) the onset of PTZ-induced seizures. It also antagonized strychnine induced seizures. The mortality was also prevented in the test group of animals. In biochemical evaluation, isolated lobeline (5, 10 and 20 mg/kg, i.p.) significantly increased the brain GABA level. And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model. Conclusions:In our findings, isolated lobeline (20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures. Also a biochemical evaluation suggested significant increase in barain GABA level at 20 mg/kg i.p. of isolated lobeline. Hence, we may propose that lobeline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.

  7. Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder.

    Science.gov (United States)

    Qi, Xin; Du, Xin; Yang, Yongxin; Du, Guijin; Gao, Peihong; Zhang, Yang; Qin, Wen; Li, Xiaodong; Zhang, Quan

    2015-01-01

    Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with internet gaming disorder (IGD), which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs) without IGD were recruited, and the balloon analog risk task (BART) was used in a functional magnetic resonance imaging experiment to evaluate the modulation of the risk level (the probability of balloon explosion) on brain activity during risky decision making in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC) during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11) scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents.

  8. Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

    Directory of Open Access Journals (Sweden)

    Xin eQi

    2015-11-01

    Full Text Available Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with Internet gaming disorder (IGD, which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs without IGD were recruited, and the Balloon Analog Risk Task (BART was used in a functional magnetic resonance imaging (fMRI experiment to evaluate the modulation of the risk level (the probability of balloon explosion on brain activity during risky decisionmaking in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11 scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents.

  9. Stable long-term chronic brain mapping at the single-neuron level.

    Science.gov (United States)

    Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

    2016-10-01

    Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

  10. Modeling the effects of noninvasive transcranial brain stimulation at the biophysical, network, and cognitive level.

    Science.gov (United States)

    Hartwigsen, Gesa; Bergmann, Til Ole; Herz, Damian Marc; Angstmann, Steffen; Karabanov, Anke; Raffin, Estelle; Thielscher, Axel; Siebner, Hartwig Roman

    2015-01-01

    Noninvasive transcranial brain stimulation (NTBS) is widely used to elucidate the contribution of different brain regions to various cognitive functions. Here we present three modeling approaches that are informed by functional or structural brain mapping or behavior profiling and discuss how these approaches advance the scientific potential of NTBS as an interventional tool in cognitive neuroscience. (i) Leveraging the anatomical information provided by structural imaging, the electric field distribution in the brain can be modeled and simulated. Biophysical modeling approaches generate testable predictions regarding the impact of interindividual variations in cortical anatomy on the injected electric fields or the influence of the orientation of current flow on the physiological stimulation effects. (ii) Functional brain mapping of the spatiotemporal neural dynamics during cognitive tasks can be used to construct causal network models. These models can identify spatiotemporal changes in effective connectivity during distinct cognitive states and allow for examining how effective connectivity is shaped by NTBS. (iii) Modeling the NTBS effects based on neuroimaging can be complemented by behavior-based cognitive models that exploit variations in task performance. For instance, NTBS-induced changes in response speed and accuracy can be explicitly modeled in a cognitive framework accounting for the speed-accuracy trade-off. This enables to dissociate between behavioral NTBS effects that emerge in the context of rapid automatic responses or in the context of slow deliberate responses. We argue that these complementary modeling approaches facilitate the use of NTBS as a means of dissecting the causal architecture of cognitive systems of the human brain.

  11. Plasma catecholamines and renin activity in wrestlers following vigorous swimming.

    Science.gov (United States)

    Vigas, M; Celko, J; Juránková, E; Jezová, D; Kvetnanský, R

    1998-01-01

    Cardiovascular and neuroendocrine responses to exercise in a physically fit and an untrained group of young healthy subjects were compared to study the significance of physical fitness for performance in a discipline for which the athletes were not trained. Ten wrestlers of national rank prepared for an international competition (age 18 years) and 9 untrained healthy males (age 21 years). Exercise consisted of 27-min swimming, freestyle, in water of 29 degrees C, with last 3 min increased to maximal effort. The blood pressure, heart rate and sublingual temperature were measured and blood samples were withdrawn before exercise, immediately after and after a 30 min period of rest. Catecholamines were analyzed by radioenzymatic method and plasma renin activity (PRA) using commercial kits. Systolic blood pressure and heart rate after swimming were increased comparably in the two groups, diastolic pressure was unchanged in the controls and decreased in the wrestlers. Plasma cortisol remained unchanged. Plasma glucose tended to increase in the controls and so decrease in wrestlers, with a significant difference between them after swimming (p < 0.05). However, plasma adrenaline was concomitantly increased in both groups (p < 0.01). Noradrenaline and PRA were increased after swimming in both the control and trained group. The increments of noradrenaline and PRA in wrestlers were significantly reduced compared to the control group (p < 0.01, p < 0.05, respectively). Higher physical fitness in athletes significantly reduced plasma noradrenaline and angiotensin responses to maximal exercise demanding special skill in work performance which had not been included in their training program. Training of wrestlers did not cause an exaggerated plasma adrenaline response to exercise.

  12. Changes in endocannabinoid and N-acylethanolamine levels in rat brain structures following cocaine self-administration and extinction training.

    Science.gov (United States)

    Bystrowska, Beata; Smaga, Irena; Frankowska, Małgorzata; Filip, Małgorzata

    2014-04-03

    Preclinical investigations have demonstrated that drugs of abuse alter the levels of lipid-based signalling molecules, including endocannabinoids (eCBs) and N-acylethanolamines (NAEs), in the rodent brain. In addition, several drugs targeting eCBs and/or NAEs are implicated in reward and/or seeking behaviours related to the stimulation of dopamine systems in the brain. In our study, the brain levels of eCBs (anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) and NAEs (oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)) were analyzed via an LC-MS/MS method in selected brain structures of rats during cocaine self-administration and after extinction training according to the "yoked" control procedure. Repeated (14days) cocaine (0.5mg/kg/infusion) self-administration and yoked drug delivery resulted in a significant decrease (ca. 52%) in AEA levels in the cerebellum, whereas levels of 2-AG increased in the frontal cortex, the hippocampus and the cerebellum and decreased in the hippocampus and the dorsal striatum. In addition, we detected increases (>150%) in the levels of OEA and PEA in the limbic areas in both cocaine treated groups, as well as an increase in the tissue levels of OEA in the dorsal striatum in only the yoked cocaine group and increases in the tissue levels of PEA in the dorsal striatum (both cocaine groups) and the nucleus accumbens (yoked cocaine group only). Compared to the yoked saline control group, extinction training (10days) resulted in a potent reduction in AEA levels in the frontal cortex, the hippocampus and the nucleus accumbens and in 2-AG levels in the hippocampus, the dorsal striatum and the cerebellum. The decreases in the limbic and subcortical areas were more apparent for rats that self-administered cocaine. Following extinction, there was a region-specific change in the levels of NAEs in rats previously injected with cocaine; a potent increase (ca. 100%) in the levels of OEA and PEA was detected in the prefrontal cortex and the

  13. Association between Serum Tissue Inhibitor of Matrix Metalloproteinase-1 Levels and Mortality in Patients with Severe Brain Trauma Injury: e94370

    National Research Council Canada - National Science Library

    Leonardo Lorente; María M Martín; Patricia López; Luis Ramos; José Blanquer; Juan J Cáceres; Jordi Solé-Violán; Jorge Solera; Judith Cabrera; Mónica Argueso; Raquel Ortiz; María L Mora; Santiago Lubillo; Alejandro Jiménez; Juan M Borreguero-León; Agustín González; Josune Orbe; José A Rodríguez; José A Páramo

    2014-01-01

    ...) play a role in neuroinflammation after brain trauma injury (TBI). Previous studies with small sample size have reported higher circulating MMP-2 and MMP-9 levels in patients with TBI, but no association between those levels and mortality...

  14. Effects of Music Aerobic Exercise on Depression and Brain-Derived Neurotrophic Factor Levels in Community Dwelling Women

    OpenAIRE

    Shu-Hui Yeh; Li-Wei Lin; Yu Kuan Chuang; Cheng-Ling Liu; Lu-Jen Tsai; Feng-Shiou Tsuei; Ming-Tsung Lee; Chiu-Yueh Hsiao; Kuender D. Yang

    2015-01-01

    A randomized clinical trial was utilized to compare the improvement of depression and brain-derived neurotrophic factor (BDNF) levels between community women with and without music aerobic exercise (MAE) for 12 weeks. The MAE group involved 47 eligible participants, whereas the comparison group had 59 participants. No significant differences were recorded in the demographic characteristics between the participants in the MAE group and the comparison group. Forty-one participants in the MAE gr...

  15. Cognitive function is related to fronto-striatal serotonin transporter levels--a brain PET study in young healthy subjects

    DEFF Research Database (Denmark)

    Madsen, Karine; Erritzøe, David Frederik; Mortensen, Erik Lykke;

    2011-01-01

    Pharmacological manipulation of serotonergic neurotransmission in healthy volunteers impacts on cognitive test performance. Specifically, markers of serotonin function are associated with attention and executive functioning, long-term memory, and general cognitive ability. The serotonin transporter...... (SERT) protein is a key regulator in the serotonin system. We hypothesized that higher performance on tests sensitive to serotonin would be associated with higher SERT levels in specific fronto-striatal brain regions....

  16. Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zukowska-Grojec, Z.; Konarska, M.; McCarty, R.

    1988-01-01

    Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. The authors studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response. Prolonged immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session. Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.

  17. Brain levels of arginine-vasotocin and isotocin in dominant and subordinate males of a cichlid fish.

    Science.gov (United States)

    Almeida, Olinda; Gozdowska, Magdalena; Kulczykowska, Ewa; Oliveira, Rui F

    2012-02-01

    The nonapeptides arginine-vasotocin (AVT) and isotocin (IT), which are the teleost homologues of arginine-vasopressin and oxytocin in mammals, have well established peripheral effects on osmoregulation and stress response, and central effects on social behavior. However, all studies that have looked so far into the relationship between these nonapeptides and social behavior have used indirect measures of AVT/IT activity (i.e. immunohistochemistry of AVT/IT immunoreactive neurons, or AVT/IT or their receptors mRNA expression with in situ hybridization or qPCR) and therefore direct measures of peptide levels in relation to social behavior are still lacking. Here we use a recently developed high-performance liquid chromatography analysis with fluorescence detection (HPLC-FL) method to quantify the levels of both AVT and IT in macro-dissected brain areas [i.e. olfactory bulbs, telencephalon, diencephalon, optic tectum, cerebellum, and hindbrain (= rhombencephalon minus cerebellum)] and pituitary of dominant and subordinate male cichlid fish (Oreochromis mossambicus). The pituitary shows higher levels of both peptides than any of the brain macroareas, and the olfactory bulbs have the highest AVT among all brain areas. Except for IT in the telencephalon there is a lack of correlations between central levels and pituitary peptide levels, suggesting an independent control of hypophysial and CNS nonapeptide secretion. There were also no correlations between AVT and IT levels either for each brain region or for the pituitary gland, suggesting a decoupled activity of the AVT and IT systems at the CNS level. Subordinate AVT pituitary levels are significantly higher than those of dominants, and dominant hindbrain IT levels are significantly higher than those of subordinates, suggesting a potential involvement of AVT in social stress in subordinate fish and of IT in the regulation of dominant behavior at the level of the hindbrain. Since in this species dominant males use urine

  18. Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection

    DEFF Research Database (Denmark)

    Müller, H; End, C; Weiss, C;

    2007-01-01

    Deleted in Malignant Brain Tumours 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds and aggregates various bacteria and viruses in vitro. Studies in adults have shown that DMBT1 is expressed mainly by mucosal epithelia and glands, in particular within the respiratory...

  19. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults

    Directory of Open Access Journals (Sweden)

    Timothy C. Durazzo

    2015-07-01

    Full Text Available Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal on cerebral perfusion (i.e., blood flow. Predominately middle-aged male (47 ± 11 years of age smokers (n = 34 and non-smokers (n = 27 were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain.

  20. Low-level electrical currents and brain indicators of behavioral activation

    Directory of Open Access Journals (Sweden)

    F. Lolas

    1977-12-01

    Full Text Available Distinguishing between slow brain potential correlates of arousal and activation on the basis of their functional role and temporal involvement during a reaction-time task, data are presented which suggest that weak electrical polarizing currents applied to the head in human subjects modify predominantly activation indicators rather than arousal ones.

  1. Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia

    DEFF Research Database (Denmark)

    Astrup, J; Symon, L; Branston, N M;

    1977-01-01

    As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory...

  2. Serum L-arginine and dimethylarginine levels in migraine patients with brain white matter lesions

    DEFF Research Database (Denmark)

    Erdélyi-Bótor, Szilvia; Komáromy, Hedvig; Kamson, David Olayinka;

    2017-01-01

    BACKGROUND/AIM: Migraine is a risk factor for the formation of silent brain white matter lesions (WMLs) that are possibly ischemic in nature. Although dysfunction of the L-arginine/nitric oxide (NO) pathway has been associated with oxidative stress and endothelial dysfunction in migraine, its rol...

  3. Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure.

    Science.gov (United States)

    Mrozek, Ségolène; Srairi, Mohamed; Marhar, Fouad; Delmas, Clément; Gaussiat, François; Abaziou, Timothée; Larcher, Claire; Atthar, Vincent; Menut, Rémi; Fourcade, Olivier; Geeraerts, Thomas

    2016-01-01

    Takotsubo cardiomyopathy can occur at the early phase of severe acute brain injuries. In the case of cardiac output decrease or shock, the optimal treatment is still a matter of debate. Due to massive stress hormone release, the infusion of catecholamines may have limited effects and may even aggravate cardiac failure. Other inotropic agents may be an option. Levosimendan has been shown to have potential beneficial effects in this setting, although milrinone has not been studied. We report a case of a young female presenting with inverted Takotsubo cardiomyopathy syndrome after severe traumatic brain injury. Due to hemodynamic instability and increasing levels of infused norepinephrine, dobutamine infusion was begun but rapidly stopped due to tachyarrhythmia. Milrinone infusion stabilized the patient's hemodynamic status and improved cardiac output without deleterious effects. Milrinone could be a good alternative when inotropes are required in Takotsubo cardiomyopathy and when dobutamine infusion is associated with tachyarrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effects of low dose endosulfan exposure on brain neurotransmitter levels in the African clawed frog Xenopus laevis.

    Science.gov (United States)

    Preud'homme, Valérie; Milla, Sylvain; Gillardin, Virginie; De Pauw, Edwin; Denoël, Mathieu; Kestemont, Patrick

    2015-02-01

    Understanding the impact of pesticides in amphibians is of growing concern to assess the causes of their decline. Among pesticides, endosulfan belongs to one of the potential sources of danger because of its wide use and known effects, particularly neurotoxic, on a variety of organisms. However, the effect of endosulfan was not yet evaluated on amphibians at levels encompassing simultaneously brain neurotransmitters and behavioural endpoints. In this context, tadpoles of the African clawed frog Xenopus laevis were submitted to four treatments during 27 d: one control, one ethanol control, and two low environmental concentrations of endosulfan (0.1 and 1 μg L(-1)). Endosulfan induced a significant increase of brain serotonin level at both concentrations and a significant increase of brain dopamine and GABA levels at the lower exposure but acetylcholinesterase activity was not modified by the treatment. The gene coding for the GABA transporter 1 was up-regulated in endosulfan contaminated tadpoles while the expression of other genes coding for the neurotransmitter receptors or for the enzymes involved in their metabolic pathways was not significantly modified by endosulfan exposure. Endosulfan also affected foraging, and locomotion in links with the results of the physiological assays, but no effects were seen on growth. These results show that low environmental concentrations of endosulfan can induce adverse responses in X. laevis tadpoles. At a broader perspective, this suggests that more research using and linking multiple markers should be used to understand the complex mode of action of pollutants.

  5. Neuropsin Expression Correlates with Dendritic Marker MAP2c Level in Different Brain Regions of Aging Mice.

    Science.gov (United States)

    Konar, Arpita; Thakur, M K

    2015-01-01

    Neuropsin (NP) is a serine protease, implicated in synaptic plasticity and memory acquisition through cleavage of synaptic adhesion molecule, L1CAM. However, NP has not been explored during brain aging that entails drastic deterioration of plasticity and memory with selective regional vulnerability. Therefore, we have analysed the expression of NP and correlated with its function via analysis of endogenous cleavage of L1CAM and level of dendritic marker MAP2c in different regions of the aging mouse brain. While NP expression gradually decreased in the cerebral cortex during aging, it showed a sharp rise in both olfactory bulb and hippocampus in adult and thereafter declined in old age. NP expression was moderate in young medulla, but undetectable in midbrain and cerebellum. It was positively correlated with L1CAM cleavage and MAP2c level in different brain regions during aging. Taken together, our study shows age-dependent regional variation in NP expression and its positive correlation with MAP2c level, suggesting the involvement of NP in MAP2c mediated alterations in dendritic morphology during aging.

  6. Exposure to static electric fields leads to changes in biogenic amine levels in the brains of Drosophila

    Science.gov (United States)

    Newland, Philip L.; Al Ghamdi, Mesfer S.; Sharkh, Suleiman; Aonuma, Hitoshi; Jackson, Christopher W.

    2015-01-01

    Natural and anthropogenic static electric fields are commonly found in the environment and can have both beneficial and harmful effects on many animals. Here, we asked how the fruitfly responds to these fields and what the consequences of exposure are on the levels of biogenic amines in the brain. When given a choice in a Y-tube bioassay Drosophila avoided electric fields, and the greater the field strength the more likely Drosophila were to avoid it. By comparing wild-type flies, flies with wings surgically removed and vestigial winged flies we found that the presence of intact wings was necessary to produce avoidance behaviour. We also show that Coulomb forces produced by electric fields physically lift excised wings, with the smaller wings of males being raised by lower field strengths than larger female wings. An analysis of neurochemical changes in the brains showed that a suite of changes in biogenic amine levels occurs following chronic exposure. Taken together we conclude that physical movements of the wings are used by Drosophila in generating avoidance behaviour and are accompanied by changes in the levels of amines in the brain, which in turn impact on behaviour. PMID:26224706

  7. The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

    Science.gov (United States)

    Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

    2008-10-01

    To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

  8. Personality traits of aggression-submissiveness and perfectionism associate with ABO blood groups through catecholamine activities.

    Science.gov (United States)

    Hobgood, Donna K

    2011-08-01

    Personality trait research has shown associations with many genes, prominently those of the catecholamine metabolism such as dopamine beta hydroxylase (DBH), catechol-O-methyltransferase (COMT), and monoamine oxidase A (MAOA). Because DBH gene is in linkage disequilibrium with ABO gene, there is reason to think that other catecholamine genes using the same substrate as DBH may also have associations with ABO blood groups, and this paper demonstrates how this may be so. Reasons include similarities in hapmap population frequency distributions, similarities in illness risks between ABO blood groups and DBH activities as well as between ABO blood groups and COMT activities and between ABO blood groups and MAOA activities. If ABO blood groups can be demonstrated to associate with all these catecholamine genes, then the catecholamine personality trait research can be applied to ABO blood groups and tested for confirmation. ABO blood typing is widely available and affords ability to test this hypothesis and thus confirm the possible joint association of personality traits of aggression-submissiveness and perfectionism to catecholamine genes and to ABO blood groups. Clinical applications and implications are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. BrainFrame: A node-level heterogeneous accelerator platform for neuron simulations.

    Science.gov (United States)

    Smaragdos, Georgios; Chatzikonstantis, Georgios; Kukreja, Rahul; Sidiropoulos, Harry; Rodopoulos, Dimitrios; Sourdis, Ioannis; Al-Ars, Zaid; Kachris, Christoforos; Soudris, Dimitrios; de Zeeuw, Chris; Strydis, Christos

    2017-07-14

    Objective: The advent of High-Performance Computing (HPC) in recent years has led to its increasing use in brain study through computational models. The scale and complexity of such models are constantly increasing, leading to challenging computational requirements. Even though modern HPC platforms can often deal with such challenges, the vast diversity of the modeling field does not permit for a homogeneous acceleration platform to effectively address the complete array of modeling requirements. Approach: In this paper we propose and build BrainFrame, a heterogeneous acceleration platform that incorporates three distinct acceleration technologies, an Intel Xeon-Phi CPU, a NVidia GP-GPU and a Maxeler Dataflow Engine. The PyNN software framework is also integrated into the platform. As a challenging proof of concept, we analyze the performance of BrainFrame on different experiment instances of a state-of-the-art neuron model, representing the Inferior-Olivary Nucleus using a biophysically-meaningful, extended Hodgkin-Huxley representation. The model instances take into account not only the neuronal-network dimensions but also different network-connectivity densities, which can drastically affect the workload's performance characteristics. Main results: The combined use of different HPC fabrics demonstrated that BrainFrame is better able to cope with the modeling diversity encountered in realistic experiments. Our performance analysis shows clearly that the model directly affects performance and all three technologies are required to cope with all the model use cases. Significance: The BrainFrame framework is designed to transparently configure and select the appropriate back-end accelerator technology for use per simulation run. The PyNN integration provides a familiar bridge to the vast number of models already available. Additionally, it gives a clear roadmap for extending the platform support beyond the proof of concept, with improved usability and directly

  10. Perception of Emotional Facial Expressions in Amyotrophic Lateral Sclerosis (ALS) at Behavioural and Brain Metabolic Level

    Science.gov (United States)

    Aho-Özhan, Helena E. A.; Keller, Jürgen; Heimrath, Johanna; Uttner, Ingo; Kassubek, Jan; Birbaumer, Niels; Ludolph, Albert C.; Lulé, Dorothée

    2016-01-01

    Introduction Amyotrophic lateral sclerosis (ALS) primarily impairs motor abilities but also affects cognition and emotional processing. We hypothesise that subjective ratings of emotional stimuli depicting social interactions and facial expressions is changed in ALS. It was found that recognition of negative emotions and ability to mentalize other’s intentions is reduced. Methods Processing of emotions in faces was investigated. A behavioural test of Ekman faces expressing six basic emotions was presented to 30 ALS patients and 29 age-, gender and education matched healthy controls. Additionally, a subgroup of 15 ALS patients that were able to lie supine in the scanner and 14 matched healthy controls viewed the Ekman faces during functional magnetic resonance imaging (fMRI). Affective state and a number of daily social contacts were measured. Results ALS patients recognized disgust and fear less accurately than healthy controls. In fMRI, reduced brain activity was seen in areas involved in processing of negative emotions replicating our previous results. During processing of sad faces, increased brain activity was seen in areas associated with social emotions in right inferior frontal gyrus and reduced activity in hippocampus bilaterally. No differences in brain activity were seen for any of the other emotional expressions. Inferior frontal gyrus activity for sad faces was associated with increased amount of social contacts of ALS patients. Conclusion ALS patients showed decreased brain and behavioural responses in processing of disgust and fear and an altered brain response pattern for sadness. The negative consequences of neurodegenerative processes in the course of ALS might be counteracted by positive emotional activity and positive social interactions. PMID:27741285

  11. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

    Directory of Open Access Journals (Sweden)

    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  12. Perception of Emotional Facial Expressions in Amyotrophic Lateral Sclerosis (ALS) at Behavioural and Brain Metabolic Level.

    Science.gov (United States)

    Aho-Özhan, Helena E A; Keller, Jürgen; Heimrath, Johanna; Uttner, Ingo; Kassubek, Jan; Birbaumer, Niels; Ludolph, Albert C; Lulé, Dorothée

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) primarily impairs motor abilities but also affects cognition and emotional processing. We hypothesise that subjective ratings of emotional stimuli depicting social interactions and facial expressions is changed in ALS. It was found that recognition of negative emotions and ability to mentalize other's intentions is reduced. Processing of emotions in faces was investigated. A behavioural test of Ekman faces expressing six basic emotions was presented to 30 ALS patients and 29 age-, gender and education matched healthy controls. Additionally, a subgroup of 15 ALS patients that were able to lie supine in the scanner and 14 matched healthy controls viewed the Ekman faces during functional magnetic resonance imaging (fMRI). Affective state and a number of daily social contacts were measured. ALS patients recognized disgust and fear less accurately than healthy controls. In fMRI, reduced brain activity was seen in areas involved in processing of negative emotions replicating our previous results. During processing of sad faces, increased brain activity was seen in areas associated with social emotions in right inferior frontal gyrus and reduced activity in hippocampus bilaterally. No differences in brain activity were seen for any of the other emotional expressions. Inferior frontal gyrus activity for sad faces was associated with increased amount of social contacts of ALS patients. ALS patients showed decreased brain and behavioural responses in processing of disgust and fear and an altered brain response pattern for sadness. The negative consequences of neurodegenerative processes in the course of ALS might be counteracted by positive emotional activity and positive social interactions.

  13. Application of fractal and grey level co-occurrence matrix analysis in evaluation of brain corpus callosum and cingulum architecture.

    Science.gov (United States)

    Pantic, Igor; Dacic, Sanja; Brkic, Predrag; Lavrnja, Irena; Pantic, Senka; Jovanovic, Tomislav; Pekovic, Sanja

    2014-10-01

    This aim of this study was to assess the discriminatory value of fractal and grey level co-occurrence matrix (GLCM) analysis methods in standard microscopy analysis of two histologically similar brain white mass regions that have different nerve fiber orientation. A total of 160 digital micrographs of thionine-stained rat brain white mass were acquired using a Pro-MicroScan DEM-200 instrument. Eighty micrographs from the anterior corpus callosum and eighty from the anterior cingulum areas of the brain were analyzed. The micrographs were evaluated using the National Institutes of Health ImageJ software and its plugins. For each micrograph, seven parameters were calculated: angular second moment, inverse difference moment, GLCM contrast, GLCM correlation, GLCM variance, fractal dimension, and lacunarity. Using the Receiver operating characteristic analysis, the highest discriminatory value was determined for inverse difference moment (IDM) (area under the receiver operating characteristic (ROC) curve equaled 0.925, and for the criterion IDM≤0.610 the sensitivity and specificity were 82.5 and 87.5%, respectively). Most of the other parameters also showed good sensitivity and specificity. The results indicate that GLCM and fractal analysis methods, when applied together in brain histology analysis, are highly capable of discriminating white mass structures that have different axonal orientation.

  14. Hypothetical high-level cognitive functions cannot be localized in the brain: another argument for a revitalized behaviorism.

    Science.gov (United States)

    Uttal, William R

    2004-01-01

    A key epistemological difference between behaviorism and cognitivism concerns their respective attitudes toward the analysis of so-called cognitive processes into functional modules. Behaviorists generally say it is not possible. Cognitivists argue that this is an achievable goal. The question has been concretized by recent developments in brain imaging technology. A consideration of the matter suggests that technical and conceptual difficulties abound in the effort to localize "high-level cognitive functions" in narrowly circumscribed regions of the brain. Some of the most serious involve the ambiguous definition of the putative mental components that are to be localized and the generally unacknowledged nonlinear complexity of both psychological processes and the brain. In addition, the imaging techniques themselves are replete with technical difficulties that raise additional questions about this particular application, even though these wonderful machines can make extraordinary contributions to our knowledge of brain anatomy and physiology. The cumulative implication of these difficulties is that the cognitive approach to the study of scientific psychology has once again set out on a search for a chimera. New approaches to behaviorism may be required to set psychology back on the correct track.

  15. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

    Directory of Open Access Journals (Sweden)

    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  16. CD38 Knockout Mice Show Significant Protection Against Ischemic Brain Damage Despite High Level Poly-ADP-Ribosylation.

    Science.gov (United States)

    Long, Aaron; Park, Ji H; Klimova, Nina; Fowler, Carol; Loane, David J; Kristian, Tibor

    2017-01-01

    Several enzymes in cellular bioenergetics metabolism require NAD(+) as an essential cofactor for their activity. NAD(+) depletion following ischemic insult can result in cell death and has been associated with over-activation of poly-ADP-ribose polymerase PARP1 as well as an increase in NAD(+) consuming enzyme CD38. CD38 is an NAD(+) glycohydrolase that plays an important role in inflammatory responses. To determine the contribution of CD38 activity to the mechanisms of post-ischemic brain damage we subjected CD38 knockout (CD38KO) mice and wild-type (WT) mice to transient forebrain ischemia. The CD38KO mice showed a significant amelioration in both histological and neurologic outcome following ischemic insult. Decrease of hippocampal NAD(+) levels detected during reperfusion in WT mice was only transient in CD38KO animals, suggesting that CD38 contributes to post-ischemic NAD(+) catabolism. Surprisingly, pre-ischemic poly-ADP-ribose (PAR) levels were dramatically higher in CD38KO animals compared to WT animals and exhibited reduction post-ischemia in contrast to the increased levels in WT animals. The high PAR levels in CD38 mice were due to reduced expression levels of poly-ADP-ribose glycohydrolase (PARG). Thus, the absence of CD38 activity can not only directly affect inflammatory response, but also result in unpredicted alterations in the expression levels of enzymes participating in NAD(+) metabolism. Although the CD38KO mice showed significant protection against ischemic brain injury, the changes in enzyme activity related to NAD(+) metabolism makes the determination of the role of CD38 in mechanisms of ischemic brain damage more complex.

  17. Differential brain and spinal cord cytokine and BDNF levels in experimental autoimmune encephalomyelitis are modulated by prior and regular exercise.

    Science.gov (United States)

    Bernardes, Danielle; Oliveira-Lima, Onésia Cristina; Silva, Thiago Vitarelli da; Faraco, Camila Cristina Fraga; Leite, Hércules Ribeiro; Juliano, Maria Aparecida; Santos, Daniel Moreira dos; Bethea, John R; Brambilla, Roberta; Orian, Jacqueline M; Arantes, Rosa Maria Esteves; Carvalho-Tavares, Juliana

    2013-11-15

    The interactions between a prior program of regular exercise and the development of experimental autoimmune encephalomyelitis (EAE)-mediated responses were evaluated. In the exercised EAE mice, although there was no effect on infiltrated cells, the cytokine and derived neurotrophic factor (BDNF) levels were altered, and the clinical score was attenuated. Although, the cytokine levels were decreased in the brain and increased in the spinal cord, BDNF was elevated in both compartments with a tendency of lesser demyelization volume in the spinal cord of the exercised EAE group compared with the unexercised.

  18. Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells

    Energy Technology Data Exchange (ETDEWEB)

    Reinhard, J.F. Jr.; Diliberto, E.J. Jr.; Viveros, O.H.; Daniels, A.J.

    1987-11-01

    Cultures of bovine adrenomedullary chromaffin cells accumulated 1-methyl-4-phenylpyridinium (MPP/sup +/) in a time- and concentration-dependent manner by a process that was prevented by desmethylimipramine. The subcellular localization of the incorporated (methyl-/sup 3/H)MPP/sup +/ was examined by differential centrifugation and sucrose density gradient fractionation and was found to be predominantly colocalized with catecholamines in chromaffin vesicles, and negligible amounts were detected within the mitochondrial fraction. When chromaffin cell membranes were made permeable with the detergent digitonin the absence of calcium, there was no increase in the release of (/sup 3/H)MPP/sup +/, indicating that there is negligible accumulation of the neurotoxin in the cytosol. Simultaneous exposure to digitonin and calcium induced cosecretion of MPP/sup +/ and catecholamines. Stimulation of the cells with nicotine released both catecholamines and MPP/sup +/ at identical rates and percentages of cellular content in a calcium-dependent manner. Last, when cells were incubated with MPP/sup +/ in the presence of tetrabenazine (an inhibitor of vesicular uptake), the chromaffin cell toxicity of MPP/sup +/ was potentiated. The authors submit that the ability of the chromaffin cells to take up and store MPP/sup +/ in the chromaffin vesicle prevents the toxin's interaction with other structures and, thus, prevents cell damage. As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP/sup +/ in the storage vesicle.

  19. Exceeding chance level by chance: The caveat of theoretical chance levels in brain signal classification and statistical assessment of decoding accuracy.

    Science.gov (United States)

    Combrisson, Etienne; Jerbi, Karim

    2015-07-30

    Machine learning techniques are increasingly used in neuroscience to classify brain signals. Decoding performance is reflected by how much the classification results depart from the rate achieved by purely random classification. In a 2-class or 4-class classification problem, the chance levels are thus 50% or 25% respectively. However, such thresholds hold for an infinite number of data samples but not for small data sets. While this limitation is widely recognized in the machine learning field, it is unfortunately sometimes still overlooked or ignored in the emerging field of brain signal classification. Incidentally, this field is often faced with the difficulty of low sample size. In this study we demonstrate how applying signal classification to Gaussian random signals can yield decoding accuracies of up to 70% or higher in two-class decoding with small sample sets. Most importantly, we provide a thorough quantification of the severity and the parameters affecting this limitation using simulations in which we manipulate sample size, class number, cross-validation parameters (k-fold, leave-one-out and repetition number) and classifier type (Linear-Discriminant Analysis, Naïve Bayesian and Support Vector Machine). In addition to raising a red flag of caution, we illustrate the use of analytical and empirical solutions (binomial formula and permutation tests) that tackle the problem by providing statistical significance levels (p-values) for the decoding accuracy, taking sample size into account. Finally, we illustrate the relevance of our simulations and statistical tests on real brain data by assessing noise-level classifications in Magnetoencephalography (MEG) and intracranial EEG (iEEG) baseline recordings. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Accelerated Curing Speed of Ethyl a-Cyanoacrylate by Polymer with Catecholamine Groups

    Institute of Scientific and Technical Information of China (English)

    张峰; 刘四委; 张艺; 许家瑞; 危岩

    2012-01-01

    Four kinds of poly(ethylene glycol) (PEG) derivatives with the similar backbone and different side groups have been synthesized successfully. When both catecholamine and double bond are tethered to polymer backbone, i.e., the PEG backbone, simultaneously, the polymer can accelerate the curing speed of ethyl a-cyanoacrylate (commer- cially available as 502) greatly under the same conditions (the curing time of such system is no more than 5 s). Probably this is due to the autoxidation of catecholamines. Through the redox-cycling, catecholamines can produce, collect free radicals, and thus initiate the free radical polymerization. Due to the fast-curing of such material when mixed with a-cyanoacrylate, we could design and develop a new bicomponent super bioglue used in the dentistry or other bioenvironment requiring super fast settlement for further surgical operations.

  1. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  2. Improvement of Motivation and Learning Level in Neuroanatomy Among Hamadan Medical Students Using Human Brain Sections

    Directory of Open Access Journals (Sweden)

    Mohammadi Roushandeh

    2015-05-01

    Full Text Available Background Using new methods in teaching anatomy could have a significant impact on students’ learning. Objectives Neuroanatomy is one of the most complicated courses in anatomy. Absence of educational assistance equipment is one the most important problems in this field. Using human brain sections could solve some of the problems and enhance students’ learning. Materials and Methods The brains of cadavers in dissection room of medicine faculty of Hamadan University of Medical Sciences were used in the present study. After fixation, the brains cut in three coronal, transverse and sagittal sections. Then, the sections were presented to one group of students in practical classes. Another group continued as control with routine educational method. The students filled out a questionnaire and declared their ideas about the new methods in Neuroanatomy education. Finally, two groups were compared for marks gained in the final exam. Results Using present method had remarkable effect on learning progress and prevention of exhaustion of students in the classroom. Moreover, it increased marvelously their ability in three-dimensional imagination in anatomy. Quantitative analysis of the final examination showed significant increase in the marks of experimental group (P < 0.05. Conclusions According to the subjective and objective results, the new method used in anatomy education had a good effect on learning of anatomy and interested students in anatomy. Besides, it decreased students’ stress at exam time. It can be a complementary method for conventional methods. It is very useful for those who need retraining courses.

  3. Long-Term Intermittent Hypoxia Elevates Cobalt Levels in the Brain and Injures White Matter in Adult Mice

    Science.gov (United States)

    Veasey, Sigrid C.; Lear, Jessica; Zhu, Yan; Grinspan, Judith B.; Hare, Dominic J.; Wang, SiHe; Bunch, Dustin; Doble, Philip A.; Robinson, Stephen R.

    2013-01-01

    Study Objectives: Exposure to the variable oxygenation patterns in obstructive sleep apnea (OSA) causes oxidative stress within the brain. We hypothesized that this stress is associated with increased levels of redox-active metals and white matter injury. Design: Participants were randomly allocated to a control or experimental group (single independent variable). Setting: University animal house. Participants: Adult male C57BL/6J mice. Interventions: To model OSA, mice were exposed to long-term intermittent hypoxia (LTIH) for 10 hours/day for 8 weeks or sham intermittent hypoxia (SIH). Measurements and Results: Laser ablation-inductively coupled plasma-mass spectrometry was used to quantitatively map the distribution of the trace elements cobalt, copper, iron, and zinc in forebrain sections. Control mice contained 62 ± 7 ng cobalt/g wet weight, whereas LTIH mice contained 5600 ± 600 ng cobalt/g wet weight (P Cobalt was concentrated within white matter regions of the brain, including the corpus callosum. Compared to that of control mice, the corpus callosum of LTIH mice had significantly more endoplasmic reticulum stress, fewer myelin-associated proteins, disorganized myelin sheaths, and more degenerated axon profiles. Because cobalt is an essential component of vitamin B12, serum methylmalonic acid (MMA) levels were measured. LTIH mice had low MMA levels (P cobalt, predominantly in the white matter. The increased cobalt is associated with endoplasmic reticulum stress, myelin loss, and axonal injury. Low plasma methylmalonic acid levels are associated with white matter injury in long-term intermittent hypoxia and possibly in obstructive sleep apnea. Citation: Veasey SC; Lear J; Zhu Y; Grinspan JB; Hare DJ; Wang S; Bunch D; Doble PA; Robinson SR. Long-term intermittent hypoxia elevates cobalt levels in the brain and injures white matter in adult mice. SLEEP 2013;36(10):1471-1481. PMID:24082306

  4. Enhancement of energy expenditure following a single oral dose of flavan-3-ols associated with an increase in catecholamine secretion.

    Directory of Open Access Journals (Sweden)

    Yusuke Matsumura

    Full Text Available Numerous clinical studies have reported that ingestion of chocolate reduces the risk of metabolic syndrome. However, the mechanisms by which this occurs remain unclear. In this murine study, the metabolic-enhancing activity of a 10 mg/kg mixture of flavan-3-ol fraction derived from cocoa (FL was compared with the same single dose of (--epicatechin (EC. Resting energy expenditure (REE was significantly increased in mice treated with the FL versus the group administered the distilled water vehicle (Cont during periods of ad libitum feeding and fasting. Mice were euthanized under the effect of anesthesia 2, 5, and 20 hr after treatment with FL or Cont while subsequently fasting. The mRNA levels of the uncoupling protein-1 (UCP-1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α in brown adipose tissue (BAT were significantly increased 2 hr after administration of FL. UCP-3 and PGC-1α in the gastrocnemius were significantly increased 2 and 5 hr after administration of the FL. The concentrations of phosphorylated AMP-activated protein kinase (AMPK 1α were found to be significant in the gastrocnemius of mice 2 and 5 hr after ingesting FL. However, these changes were not observed following treatment with EC. Plasma was collected for measurement of catecholamine levels in other animals euthanized by decapitation 2 and 4 hr after their respective group treatment. Plasma adrenaline level was significantly elevated 2 hr after treatment with FL; however, this change was not observed following the administration of EC alone. The present results indicated that FL significantly enhanced systemic energy expenditure, as evidenced by an accompanying increase in the type of gene expression responsible for thermogenesis and lipolysis, whereas EC exhibited this less robustly or effectively. It was suggested the possible interaction between thermogenic and lipolytic effects and the increase in plasma catecholamine concentrations

  5. Differential circadian catecholamine and cortisol responses between healthy women with and without a parental history of hypertension.

    Science.gov (United States)

    James, Gary D; Alfarano, Alexandria S; van Berge-Landry, Helene M

    2014-01-01

    Previous studies suggest that otherwise healthy individuals who have a parental history of hypertension (PH+) have an accentuated reactive rise in catecholamines and cortisol to laboratory stressors as well as elevated plasma levels when compared with those with no parental history (PH-); however, few, if any, studies have evaluated whether parental history affects the responses of these hormones to changing environmental circumstances in everyday life. The purpose of this study was to compare urinary catecholamine (epinephrine and norepinephrine) and cortisol excretion and ambulatory blood pressures (BPs) across three daily microenvironments between women with and without a parental history of hypertension. The women in the study (PH+, N = 62, age = 35.2 ± 9.1; PH-, N = 72, age = 33.8 ± 10.0) worked in clerical, technical, or professional positions at a major medical center in New York City. Urinary hormone excretion rates and ambulatory BP were measured across three daily microenvironments: work (11 am to 3 p.m.), home (approximately 6 p.m. to 10 p.m.), and during sleep (approximately 10 p.m. to 6 a.m.). History group comparisons by microenvironment were made using repeated-measures ANCOVA and ANOVA analyses. The results show that epinephrine excretion among PH+ women was 36% higher than PH- women (P < 0.008) over the entire day and that nocturnal cortisol excretion was also greater among PH+ women (P < 0.045). PH+ women also had statistically significantly higher systolic (4 mm Hg higher; P < 0.01) and diastolic (2 mm Hg higher, P < 0.03) BP when compared with PH- women across all daily microenvironments. These findings suggest that there may be genetically linked mechanisms which elevate tonic epinephrine levels and nocturnal cortisol levels that contribute to elevating circadian BP. © 2014 Wiley Periodicals, Inc.

  6. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

    Science.gov (United States)

    Lenoir, Magalie

    2012-01-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  7. Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders.

    Science.gov (United States)

    Goldstein, David S; Kopin, Irwin J; Sharabi, Yehonatan

    2014-12-01

    Several neurodegenerative diseases involve loss of catecholamine neurons-Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of "autotoxicity"-inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the "catecholaldehyde hypothesis" for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis. Published by Elsevier Inc.

  8. Copper-mediated oxidative degradation of catecholamines and oxidative damage of protein

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, P.R.; Harria, M.I.N.; Felix, J.M.; Hoffmann, M.E. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia

    1997-12-31

    Full text. Degradative oxidation of catecholamines has been a matter of large interest in recent years due to the evidences associating their autoxidation with the etiology of neurotoxic and cardiotoxic processes. In this work we present data on the degradative oxidation of catecholamines of physiological importance: isoproterenol (IP), epinephrine (EP), norepinephrine (NEP), deoxyepinephrine (DEP) and dopamine (DA). The degradative oxidation of the catecholamines was followed by measurement of spectral changes and oxygen consumption by neutral aqueous solutions. The data show that Cu{sup 2+} strongly accelerated the rate of catecholamine oxidation, following the decreasing order; EP>DEP>IP>NEP>DA. The production of superoxide anion radical during catecholamine oxidation was very slow, even in the presence of Cu{sup 2+}. The ability of IP to induce damages on bovine serum albumin (BSA) was determined by measuring the formation of carbonyl-groups in the protein, detected by reduction with tritiated Na BH{sub 4}. The incubation of BSA with IP (50-500{mu}M), in the presence of 100{mu}M Cu{sup 2+} leaded to an increased and dose dependent {sup 3} H-incorporation by the oxidized protein. The production of oxidative damage by IP/Cu{sup 2+} was accompanied by marked BSA fragmentation, detected by SDS-polyacrylamide gel dependent (25-400{mu}M IP) des appearance of the original BSA band and appearance of smaller fragments spread in the gel, when incubation has been done in the presence of 100{mu}M Cu{sup 2+}. These results suggest that copper-catalysed oxidative degradation of proteins induced by catecholamines might be critically involved in the toxic action of these molecules

  9. Variational level set approach for automatic correction of multiplicative and additive intensity inhomogeneities in brain MR Images.

    Science.gov (United States)

    Verma, Nishant; Cowperthwaite, Matthew C; Markey, Mia K

    2012-01-01

    Retrospective correction of intensity inhomogeneities in magnetic resonance images of the brain is an essential pre-processing step before any sophisticated image analysis task can be performed. A popular choice when defining the degradation model in MR images is to use multiplicative intensity inhomogeneities that slowly varying across the image domain; this approach has been extensively used for bias field estimation. However, such a multiplicative model is often insufficient given that some of the most dominant physical causes of intensity inhomogeneities in MRI (such as nonuniform excitation strength) have a non-linear relationship with the receptor signal intensity. In this study, we consider a linear image degradation model with multiplicative and additive intensity inhomogeneity components. We propose a variational level sets approach that combines estimation of intensity inhomogeneity components during the image segmentation process. The evaluation of proposed approach on real MR image datasets demonstrate accurate estimation of multiplicative and additive intensity inhomogeneities improving brain tissue segmentation.

  10. Clinical motivation for P-31 MRS studies on the myocardial energy metabolism of brain dead cats

    NARCIS (Netherlands)

    Bruinsma, GJBB; van Echteld, CJA

    2003-01-01

    Hemodynamic instability of the brain dead potential heart donor is an exclusion criterion for heart donation for transplantation. Based on the results of myocardial biopsies it has been reported that brain death-related catecholamine induced damage of the heart causes depletion of high-energy phosph

  11. Effects of Increase in Amplitude of Occipital Alpha & Theta Brain Waves on Global Functioning Level of Patients with GAD.

    Science.gov (United States)

    Dadashi, Mohsen; Birashk, Behrooz; Taremian, Farhad; Asgarnejad, Ali Asghar; Momtazi, Saeed

    2015-01-01

    The basic objective of this study is to investigate the effects of alpha and theta brain waves amplitude increase in occipital area on reducing the severity of symptoms of generalized anxiety disorder and to increase the global functioning level in patients with GAD. This study is a quasi-experimental study with pre-test and post-test with two groups. For this purpose, 28 patients who had been referred to Sohrawardi psychiatric and clinical psychology center in Zanjan were studied based on the interview with the psychiatrist, clinical psychologist and using clinical diagnostic criteria for the Diagnostic and Statistical Manual of Mental Disorders text revision - the DSM-IV-TR Fourth Edition diagnosis of GAD, 14 subjects were studied in neurofeedback treatment group and 14 subjects in the waiting list group. Patients in both groups were evaluated at pre-test and post-test with General Anxiety Disorder Scale (GAD-7) and Global Assessment Functioning Scale (GAFs). The treatment group received fifteen 30-minute alpha training sessions and fifteen 30-minute theta brain training sessions in occipital area by neurofeedback training (treatment group). This evaluation was performed according to the treatment protocol to increase the alpha and theta waves. And no intervention was done in the waiting list group. But due to ethical issues after the completion of the study all the subjects in the waiting list group were treated. The results showed that increase of alpha and theta brain waves amplitude in occipital area in people with GAD can increase the global functioning level and can reduce symptoms of generalized anxiety disorder in a treatment group, but no such change was observed in the waiting list group. Increase of alpha and theta brain waves amplitude in occipital area can be useful in the treatment of people with GAD.

  12. [Stimulation of mitochondrial oxidative enzymes in acute cooling and its catecholamine mechanisms].

    Science.gov (United States)

    Kulinskiĭ, V I; Medvedev, A I; Kuntsevich, A K

    1986-01-01

    Acute cooling of rats led to stimulation of NAD+-dependent isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH) and NAD(P)+-transhydrogenase (TH) but did not affect the NADP+-ICDH activity in liver, heart and skeletal muscle mitochondria. After pretreatment of the animals with propranolol the stimulating effect was decreased, thus suggesting that endogenous catecholamines and beta-adrenoreceptors are of importance in activation of NAD+-ICDH, SDH and TH. The effects of cooling, noradrenaline and cAMP did not summarize. Role of catecholamines in stimulation of mitochondrial oxidative enzymes under conditions of cooling is discussed.

  13. A dopaminergic receptor modulates catecholamine release from the cat adrenal gland.

    Science.gov (United States)

    Artalejo, A R; García, A G; Montiel, C; Sánchez-García, P

    1985-01-01

    Nicotine evokes the release of catecholamines from perfused cat adrenal glands in a concentration-dependent manner, the median effective concentration for nicotine being 5 microM. Two 2 min pulses of 5 microM-nicotine, 40 min apart (S1 and S2) gave net catecholamine outputs of 7.64 and 3.55 micrograms/8 min, respectively. The ratio S2/S1 in control glands was 0.5. Increasing concentrations of apomorphine (1-10 microM) markedly inhibited catecholamine release during the second nicotine pulse (S2). At 1 microM-apomorphine, the release during S2 was significantly reduced to 16% of S1; with 10 microM-apomorphine, the secretory response was reduced further to only 3% of S1, the ratio S2/S1 being 0.03. The presence of haloperidol, sulpiride or picobenzide (each 0.5 microM) during S2, completely reversed the inhibition of catecholamine release produced by apomorphine. Haloperidol itself increased the nicotinic secretory response during S2; so, while the ratio S2/S1 was 0.5 in control conditions, this ratio increased significantly to 0.95 if haloperidol (0.5 microM) was present during S2, suggesting that the presence of this dopaminergic antagonist removed a negative feed-back mechanism that inhibits nicotine-evoked catecholamine release. If present during S2, dopamine (1 microM) also markedly inhibited catecholamine release evoked by nicotine; this inhibition was again reversed by 0.5 microM-haloperidol. Neither the opiate antagonist naloxone nor the alpha-adrenoceptor blocking agent phentolamine (at concentrations of 0.5-5 microM) affected the inhibition by apomorphine of the secretory response to nicotine. These data strongly suggest that the cat adrenal medulla chromaffin cell membrane contains a dopaminergic receptor which modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. The fact that dopamine is released in measurable amounts, together with adrenaline and noradrenaline, from perfused cat adrenal glands in response

  14. Age-dependent neuroplasticity mechanisms in Alzheimer Tg2576 mice following modulation of brain amyloid-β levels.

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    Anna M Lilja

    Full Text Available The objective of this study was to investigate the effects of modulating brain amyloid-β (Aβ levels at different stages of amyloid pathology on synaptic function, inflammatory cell changes and hippocampal neurogenesis, i.e. processes perturbed in Alzheimer's disease (AD. Young (4- to 6-month-old and older (15- to 18-month-old APP(SWE transgenic (Tg2576 mice were treated with the AD candidate drug (+-phenserine for 16 consecutive days. We found significant reductions in insoluble Aβ1-42 levels in the cortices of both young and older transgenic mice, while significant reductions in soluble Aβ1-42 levels and insoluble Aβ1-40 levels were only found in animals aged 15-18 months. Autoradiography binding with the amyloid ligand Pittsburgh Compound B ((3H-PIB revealed a trend for reduced fibrillar Aβ deposition in the brains of older phenserine-treated Tg2576 mice. Phenserine treatment increased cortical synaptophysin levels in younger mice, while decreased interleukin-1β and increased monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels were detected in the cortices of older mice. The reduction in Aβ1-42 levels was associated with an increased number of bromodeoxyuridine-positive proliferating cells in the hippocampi of both young and older Tg2576 mice. To determine whether the increased cell proliferation was accompanied by increased neuronal production, the endogenous early neuronal marker doublecortin (DCX was examined in the dentate gyrus (DG using immunohistochemical detection. Although no changes in the total number of DCX(+-expressing neurons were detected in the DG in Tg2576 mice at either age following (+-phenserine treatment, dendritic arborization was increased in differentiating neurons in young Tg2576 mice. Collectively, these findings indicate that reducing Aβ1-42 levels in Tg2576 mice at an early pathological stage affects synaptic function by modulating the maturation and plasticity of newborn neurons in

  15. Negative correlation between brain glutathione level and negative symptoms in schizophrenia: a 3T 1H-MRS study.

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    Daisuke Matsuzawa

    Full Text Available BACKGROUND: Glutathione (GSH, a major intracellular antioxidant, plays a role in NMDA receptor-mediated neurotransmission, which is involved in the pathophysiology of schizophrenia. In the present study, we aimed to investigate whether GSH levels are altered in the posterior medial frontal cortex of schizophrenic patients. Furthermore, we examined correlations between GSH levels and clinical variables in patients. METHODS AND FINDINGS: Twenty schizophrenia patients and 16 age- and gender-matched normal controls were enrolled to examine the levels of GSH in the posterior medial frontal cortex by using 3T SIGNA EXCITE (1H-MRS with the spectral editing technique, MEGA-PRESS. Clinical variables of patients were assessed by the Global Assessment of Functioning (GAF, Scale for the Assessment of Negative Symptoms (SANS, Brief Psychiatric Rating Scale (BPRS, Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS, and five cognitive performance tests (Word Fluency Test, Stroop Test, Trail Making Test, Wisconsin Card Sorting Test and Digit Span Distractibility Test. Levels of GSH in the posterior medial frontal cortex of schizophrenic patients were not different from those of normal controls. However, we found a significant negative correlation between GSH levels and the severity of negative symptoms (SANS total score and negative symptom subscore on BPRS in patients. There were no correlations between brain GSH levels and scores on any cognitive performance test except Trail Making Test part A. CONCLUSION: These results suggest that GSH levels in the posterior medial frontal cortex may be related to negative symptoms in schizophrenic patients. Therefore, agents that increase GSH levels in the brain could be potential therapeutic drugs for negative symptoms in schizophrenia.

  16. Sex differences in ibogaine antagonism of morphine-induced locomotor activity and in ibogaine brain levels and metabolism.

    Science.gov (United States)

    Pearl, S M; Hough, L B; Boyd, D L; Glick, S D

    1997-08-01

    The present study demonstrates that the putative antiaddictive agent ibogaine produces more robust behavioral effects in female than in male rats and that these behavioral differences correlate with higher levels of ibogaine in the brain and plasma of female rats. There were no differences in basal locomotor activity between the sexes, and the response of rats to ibogaine differed between the sexes even in the absence of morphine. Five h after receiving ibogaine (40 mg/kg, i.p.). antagonism of morphine-induced locomotor activity was evident in female but not in male rats. Either 19 h after administration of ibogaine (10-60 mg/kg, i.p.), or one h after administration of noribogaine (5-40 mg/kg, i.p.), a suspected metabolite, antagonism of morphine was significantly greater in female than in male rats. Brain and plasma levels of ibogaine (1 h) and noribogaine (5 h), measured by gas chromatography-mass spectrometry, were greater in females as compared with males receiving the same dose of ibogaine. Levels of both ibogaine and noribogaine were substantially lower at 19 h than at earlier times after ibogaine administration, contrary to a previous study in humans. For both sexes, subcutaneous administration of ibogaine (40 mg/kg, i.p., 19 h) produced greater antagonism of morphine-induced locomotor activity than did a comparable intraperitoneal injection, consistent with previous studies from this laboratory demonstrating that the former route of administration produces higher levels of ibogaine in the brain. These data show that there are sex differences in the effects of ibogaine and that this may be due to decreased bioavailability of ibogaine in males as compared to females.

  17. Role of catecholamines and nitric oxide on pigment displacement of the chromatophores of freshwater snakehead teleost fish, Channa punctatus.

    Science.gov (United States)

    Biswas, Saikat P; Jadhao, Arun G; Palande, Nikhil V

    2014-04-01

    We are reporting for the first time that the catecholamines (adrenaline and noradrenaline) inhibit the effect of nitric oxide (NO) on melanosome dispersion in freshly isolated scales of the freshwater snakehead fish, Channa punctatus. We studied the effect of NO and catecholamines on the pigment displacement by observing the changes in the melanophore index. The scales when treated with solution containing NO donor sodium nitroprusside (SNP) showed dispersion of melanosomes, whereas NO synthase blocker N-omega-Nitro-L-arginine suppresses this action of SNP. Treatment with adrenaline and noradrenaline on the isolated scales caused aggregation of melanosomes. Scales treated with solution containing catecholamines and SNP resulted in aggregation of melanosomes suggesting that catecholamines mask the effect of SNP. These results suggest that the catecholamines are inhibiting the effect of NO and causing the aggregation of the melanosomes may be via surface receptors.

  18. In vitro Catecholamine Exposure Produces Variable Effects on the B7 Costimulatory Pathway in Human Monocytic Cells

    Science.gov (United States)

    Salicru, A. N.; Crucian, B.; Sams, Clarence; Actor, J. K.; Marshall, G. D., Jr.

    2006-01-01

    Catecholamines have been associated with immunomodulation of the adaptive immune system towards a Th2 response in vitro. We therefore examined the role of in vitro epinephrine (EPI) and norepinephrine (NE) exposure on the B7 costimulatory expression of antigen presenting cells (APC) from human monocytic cell lines and human peripheral blood mononuclear cells (PBMC). THP1 monocytic cells and CD14+ cells from normal human PBMC were stimulated with lipopolysaccharide (LPS) and incubated with physiologic stress levels (10(exp -6) - 10(exp -8)M) of EPI or NE for 24 hours. Cells were subsequently stained with CD80 FITC, CD86 PE, and CD14 PC5 antibodies and analyzed by flow cytometry for changes in fluorescence and mean fluorescence intensity (MFI). Exposure of THP1 to EPI in vitro at concentrations of 10(exp -6), 10(exp -7) and 10(exp -8)M significantly decreased mean CD80 from 42 plus or minus 0.7% to 11 plus or minus 0.44%, 19.1 plus or minus 2.0%, and 30.7 plus or minus 2.1% expression, respectively (p less than 0.01). In addition, CD86 expression increased with EPI at 10(exp -6), 10(exp -7) and 10(exp -8) M from 9.2 plus or minus 0.52% to 41 plus or minus 3.8%, 26.4 plus or minus 1.9%, and 15.74 plus or minus 1.8% expression, respectively (p less than 0.01). Similar results for mean CD80 and CD86 percent expression were observed for CD14+ cells from PBMC with a sample size of N = 6 and for NE when substituted for EPI. The data show that in vitro exposure to catecholamines significantly decreases %CD86 expression and significantly increases %CD86 expression in THP1 cells and human CD14+ APC. Previous studies have suggested an association between increased CD86 expression and TH2 activity. Thus, these data suggest that immunomodulation by catecholamines results in part by the variable effects of the B7 costimulatory pathway in APC.

  19. CARDIAC RISK STRATIFICATION IN PATIENTS WITH CONGESTIVE HEART FAILURE: A CATECHOLAMINES-β- ADRENOCEPTOR-cAMP PATHWAY

    Institute of Scientific and Technical Information of China (English)

    Ying-xin Peng; Jiang Shan; Su-jun Zhang; Chun-li Rong; Jun-ping Li; Na Wang; Hao Xue; Shi-ling Zheng; Min Wu

    2005-01-01

    Objective To investigate the stratification risk of catecholamines-β-adrenoceptor (β-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF).Methods A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE)and epinephrine (E), lymphocytes β-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered.Results The period between the initial entry and the last follow-up measurement were 51± 16 months, the total duration of clinical follow-up after the last measurement were 14±8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the 0.017), but difference was not significant between the β-AR density below and above median.Conclusions Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.

  20. Genetic effects on source level evoked and induced oscillatory brain responses in a visual oddball task.

    Science.gov (United States)

    Antonakakis, Marios; Zervakis, Michalis; van Beijsterveldt, Catharina E M; Boomsma, Dorret I; De Geus, Eco J C; Micheloyannis, Sifis; Smit, Dirk J A

    2016-02-01

    Stimuli in simple oddball target detection paradigms cause evoked responses in brain potential. These responses are heritable traits, and potential endophenotypes for clinical phenotypes. These stimuli also cause responses in oscillatory activity, both evoked responses phase-locked to stimulus presentation and phase-independent induced responses. Here, we investigate whether phase-locked and phase-independent oscillatory responses are heritable traits. Oscillatory responses were examined in EEG recordings from 213 twin pairs (91 monozygotic and 122 dizygotic twins) performing a visual oddball task. After group Independent Component Analysis (group-ICA) and time-frequency decomposition, individual differences in evoked and induced oscillatory responses were compared between MZ and DZ twin pairs. Induced (phase-independent) oscillatory responses consistently showed the highest heritability (24-55%) compared to evoked (phase-locked) oscillatory responses and spectral energy, which revealed lower heritability at 1-35.6% and 4.5-32.3%, respectively. Since the phase-independent induced response encodes functional aspects of the brain response to target stimuli different from evoked responses, we conclude that the modulation of ongoing oscillatory activity may serve as an additional endophenotype for behavioral phenotypes and psychiatric genetics.

  1. MW151 Inhibited IL-1β Levels after Traumatic Brain Injury with No Effect on Microglia Physiological Responses.

    Science.gov (United States)

    Bachstetter, Adam D; Zhou, Zhengqiu; Rowe, Rachel K; Xing, Bin; Goulding, Danielle S; Conley, Alyssa N; Sompol, Pradoldej; Meier, Shelby; Abisambra, Jose F; Lifshitz, Jonathan; Watterson, D Martin; Van Eldik, Linda J

    2016-01-01

    A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI). In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a closed head injury model of mild TBI suppressed acute cytokine up-regulation and downstream cognitive impairment. Here, we report results from a diffuse brain injury model in mice using midline fluid percussion. Low dose (0.5-5.0 mg/kg) administration of MW151 suppresses interleukin-1 beta (IL-1β) levels in the cortex while sparing reactive microglia and astrocyte responses. To probe molecular mechanisms, we used live cell imaging of the BV-2 microglia cell line to demonstrate that MW151 does not affect proliferation, migration, or phagocytosis of the cells. Our results provide insight into the roles of glial responses to brain injury and indicate the feasibility of using appropriate dosing for selective therapeutic modulation of injurious IL-1β increases while sparing other glial responses to injury.

  2. MW151 Inhibited IL-1β Levels after Traumatic Brain Injury with No Effect on Microglia Physiological Responses.

    Directory of Open Access Journals (Sweden)

    Adam D Bachstetter

    Full Text Available A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI. In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a closed head injury model of mild TBI suppressed acute cytokine up-regulation and downstream cognitive impairment. Here, we report results from a diffuse brain injury model in mice using midline fluid percussion. Low dose (0.5-5.0 mg/kg administration of MW151 suppresses interleukin-1 beta (IL-1β levels in the cortex while sparing reactive microglia and astrocyte responses. To probe molecular mechanisms, we used live cell imaging of the BV-2 microglia cell line to demonstrate that MW151 does not affect proliferation, migration, or phagocytosis of the cells. Our results provide insight into the roles of glial responses to brain injury and indicate the feasibility of using appropriate dosing for selective therapeutic modulation of injurious IL-1β increases while sparing other glial responses to injury.

  3. Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Tatiana Lauxen Peruzzolo

    2015-01-01

    Full Text Available Pediatric bipolar disorder (PBD is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder. We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

  4. Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder.

    Science.gov (United States)

    Lauxen Peruzzolo, Tatiana; Anes, Mauricio; Kohmann, Andre de Moura; Souza, Ana Claudia Mércio Loredo; Rodrigues, Ramiro Borges; Brun, Juliana Basso; Peters, Roberta; de Aguiar, Bianca Wollenhaupt; Kapczinski, Flavio; Tramontina, Silzá; Rohde, Luis Augusto Paim; Zeni, Cristian Patrick

    2015-01-01

    Pediatric bipolar disorder (PBD) is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF) is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder). We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm(3), respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

  5. Stereotactic radiosurgery for newly diagnosed brain metastases. Comparison of three dose levels

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Hornung, Dagmar [University Medical Center Hamburg-Eppendorf, Department of Radiation Oncology, Hamburg (Germany); Blanck, Oliver [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Martens, Kristina [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Center for Integrative Psychiatry, Luebeck (Germany); Khoa, Mai Trong [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, Ngo Thuy [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Hueppe, Michael [University of Luebeck, Department of Anesthesiology, Luebeck (Germany); Terheyden, Patrick [University of Luebeck, Department of Dermatology, Luebeck (Germany); Gliemroth, Jan [University of Luebeck, Department of Neurosurgery, Luebeck (Germany); Schild, Steven E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale (United States)

    2014-09-15

    Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases. In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size (< 15 vs. ≥ 15 mm), extracranial metastases (no vs. yes), RPA class (1 vs. 2), and interval of cancer diagnosis to SRS (≤ 24 vs. > 24 months). For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79 %, respectively (p < 0.001). The SRS dose maintained significance on multivariate analysis (risk ratio: 2.25; 95 % confidence interval: 1.56-3.29; p < 0.001). On intergroup comparisons of local control, 20 Gy was superior to 13-16 Gy (p < 0.001) but not to 18 Gy (p = 0.12); 18 Gy showed a strong trend toward better local control when compared with 13-16 Gy (p = 0.059). Freedom from new brain metastases (p = 0.57) and survival (p = 0.15) were not associated with SRS dose in the univariate analysis. SRS doses of 18 Gy and 20 Gy resulted in better local control than 13-16 Gy. However, 20 Gy and 18 Gy must be compared again in a larger cohort of patients. Freedom from new brain metastases and survival were not associated with SRS dose. (orig.) [German] Drei Dosislevel bei der alleinigen stereotaktischen Radiochirurgie (SRS) von 1 bis 3 neu diagnostizierten Hirnmetastasen wurden hinsichtlich lokaler Kontrolle der bestrahlten Metastasen, Nichtauftreten neuer Hirnmetastasen und Gesamtueberleben verglichen. Nach der am Rand der Metastasen applizierten SRS-Dosis wurden 134 Patienten den Gruppen 13

  6. Effects of outcome on the covariance between risk level and brain activity in adolescents with internet gaming disorder

    Directory of Open Access Journals (Sweden)

    Xin Qi

    2016-01-01

    Full Text Available Individuals with internet gaming disorder (IGD often have impaired risky decision-making abilities, and IGD-related functional changes have been observed during neuroimaging studies of decision-making tasks. However, it is still unclear how feedback (outcomes of decision-making affects the subsequent risky decision-making in individuals with IGD. In this study, twenty-four adolescents with IGD and 24 healthy controls (HCs were recruited and underwent functional magnetic resonance imaging while performing the balloon analog risk task (BART to evaluate the effects of prior outcomes on brain activity during subsequent risky decision-making in adolescents with IGD. The covariance between risk level and activation of the bilateral ventral medial prefrontal cortex, left inferior frontal cortex, right ventral striatum (VS, left hippocampus/parahippocampus, right inferior occipital gyrus/fusiform gyrus and right inferior temporal gyrus demonstrated interaction effects of group by outcome (P < 0.05, AlphaSim correction. The regions with interactive effects were defined as ROI, and ROI-based intergroup comparisons showed that the covariance between risk level and brain activation was significantly greater in adolescents with IGD compared with HCs after a negative outcome occurred (P < 0.05. Our results indicated that negative outcomes affected the covariance between risk level and activation of the brain regions related to value estimation (prefrontal cortex, anticipation of rewards (VS, and emotional-related learning (hippocampus/parahippocampus, which may be one of the underlying neural mechanisms of disadvantageous risky decision-making in adolescents with IGD.

  7. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

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    Ericksen Mielle Borba

    2016-12-01

    Full Text Available Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD pathology. Serum brain-derived neurotrophic factor (BDNF reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]. Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  8. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    Science.gov (United States)

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes

    2016-01-01

    Background/Aims Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Methods Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction. PMID:28101102

  9. The Human Brain Does Not Need High Levels of Motivation to Learn a Foreign Language: Motivation Has Had its Day

    Directory of Open Access Journals (Sweden)

    Kieran Green

    2016-10-01

    Full Text Available Language is nature in action and something humans do.  This literature review presents evidence from the literature that suggests that learning a foreign language in a classroom situation does not require high levels of student motivation.  It is instead suggested that high levels of motivation are needed to make progress when a teacher is using traditional teaching methods.  It is shown that all healthy human brains are excellent at learning and using language, and high levels of motivation to learn a foreign language are not required if teaching practices and materials replicate natural learning experiences, and class participation is ensured.  This work is of great importance to teachers as it demonstrates that teachers would help students more by investing their time in developing class materials than by worrying about student motivation. Keywords:  foreign language, cognitive linguistics, language evolution, language learnability, language usability, motivation

  10. Effects of aerobic exercise training on peripheral brain-derived neurotrophic factor and eotaxin-1 levels in obese young men

    OpenAIRE

    Cho, Su Youn; Roh, Hee Tae

    2016-01-01

    [Purpose] The aim of the present study was to investigate the effects of aerobic exercise training on the levels of peripheral brain-derived neurotrophic factor and eotaxin-1 in obese young men. [Subjects and Methods] The subjects included sixteen obese young men with a body mass index greater than 25 kg/m2. They were randomly divided between control and exercise groups (n = 8 in each group). The exercise group performed treadmill exercise for 40 min, 3 times a week for 8 weeks at the intensi...

  11. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Hoejman, Pernille

    2015-01-01

    UNLABELLED: The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment......-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU...

  12. Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA

    Science.gov (United States)

    Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

    2015-01-01

    A number of contaminants affect fish health, including mercury and selenium, and the selenium: mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium: mercury molar ratios by tissues. Total mercury averaged 0.32 ± 0.02 ppm wet weight in edible muscle and 0.09 ± 0.01 ppm in brain. Selenium concentration averaged 0.37 ± 0.03 in muscle and 0.36 ± 0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium: mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium: mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. PMID:23202378

  13. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten;

    2011-01-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor....... Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression...... in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p

  14. Effects of imipramine of the orthostatic changes in blood pressure, heart rate and plasma catecholamines

    DEFF Research Database (Denmark)

    Nielsen, J R; Johansen, Torben; Arentoft, A

    1983-01-01

    The effect of imipramine on the orthostatic changes in heart rate, blood pressure and plasma catecholamines were examined in six healthy male subjects on two occasions on high sodium balance (Na+ excretion greater than 120 mmol per day) and on low sodium balance (Na+ excretion less than 110 mmol...

  15. Fully automated high-performance liquid chromatographic assay for the analysis of free catecholamines in urine.

    Science.gov (United States)

    Said, R; Robinet, D; Barbier, C; Sartre, J; Huguet, C

    1990-08-24

    A totally automated and reliable high-performance liquid chromatographic method is described for the routine determination of free catecholamines (norepinephrine, epinephrine and dopamine) in urine. The catecholamines were isolated from urine samples using small alumina columns. A standard automated method for pH adjustment of urine before the extraction step has been developed. The extraction was performed on an ASPEC (Automatic Sample Preparation with Extraction Columns, Gilson). The eluate was collected in a separate tube and then automatically injected into the chromatographic column. The catecholamines were separated by reversed-phase ion-pair liquid chromatography and quantified by fluorescence detection. No manual intervention was required during the extraction and separation procedure. One sample may be run every 15 min, ca. 96 samples in 24 h. Analytical recoveries for all three catecholamines are 63-87%, and the detection limits are 0.01, 0.01, and 0.03 microM for norepinephrine, epinephrine and dopamine, respectively, which is highly satisfactory for urine. Day-to-day coefficients of variation were less than 10%.

  16. Concepts of scientific integrative medicine applied to the physiology and pathophysiology of catecholamine systems.

    Science.gov (United States)

    Goldstein, David S

    2013-10-01

    This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine-related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body's monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback-regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems-especially Parkinson disease-and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post-genome era.

  17. Pedophilia is accompanied by increased plasma concentrations of catecholamines, in particular epinephrine.

    Science.gov (United States)

    Maes, M; De Vos, N; Van Hunsel, F; Van West, D; Westenberg, H; Cosyns, P; Neels, H

    2001-08-05

    Plasma epinephrine and norepinephrine concentrations were measured in pedophiles and normal men both in placebo conditions and after administration of meta-chlorophenylpiperazine (mCPP), a post-synaptic 5-HT2 receptor agonist. The plasma concentrations of catecholamines, in particular epinephrine, were significantly increased in pedophiles. It is concluded that pedophiles may have an increased activity of the sympathoadrenal system.

  18. Sympathetic nervous activity in cirrhosis. A survey of plasma catecholamine studies

    DEFF Research Database (Denmark)

    Henriksen, J H; Ring-Larsen, H; Christensen, N J

    1985-01-01

    in this condition. This may especially apply to the sympathetic tone in the kidney, as evaluated by regional measurements of noradrenaline overflow. Hepatic elimination of catecholamines is only slightly reduced. Activati