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The noradrenergic (NE) locus coeruleus (LC) is vulnerable to hyperphosphorylated tau, and dysregulated NE-metabolism is linked to greater tau and disease progression. We investigated whether elevated NE-metabolism alone predicts memory decline or whether concomitant presence of tau and amyloid-β is required. Among 114 memory clinic participants, time trends (max. six years) showed dose-response declines in learning across groups with elevated NE-metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) with no, one, or two Alzheimer’s disease biomarkers; and no decline in the low MHPG group. Elevated MHPG is required and sufficient to detect learning declines, supporting a pathophysiologic model including the LC-NE system contributing to initial Alzheimer’s disease-related processes.

Objectives: The neurobiological mechanisms linking obesity to emotional distress remain largely undiscovered.Methods: In this pilot study, we combined positron emission tomography, using the norepinephrine transporter (NET) tracer [11C]-O-methylreboxetine, with functional connectivity magnetic resonance imaging, the Beck depression inventory (BDI), and the impact of weight on quality of life–Lite questionnaire (IWQOL–Lite), to investigate the role of norepinephrine in the severity of depression (BDI), as well as in the loss of emotional well-being with body weight (IWQOL–Lite).Results: In a small group of lean-to-morbidly obese individuals (n=20), we show that an increased body mass index (BMI) is related to a lowered NET availability within the hypothalamus, known as the brain’s homeostatic control site. The hypothalamus displayed a strengthened connectivity in relation to the individual hypothalamic NET availability to the anterior insula/frontal operculum, as well as the medial orbitofrontal cortex, assumed to host the primary and secondary gustatory cortex, respectively (n=19). The resting-state activity in these two regions was correlated positively to the BMI and IWQOL–Lite scores, but not to the BDI, suggesting that the higher the resting-state activity in these regions, and hence the higher the BMI, the stronger the negative impact of the body weight on the individual’s emotional well-being was.Conclusions: This pilot study suggests that the loss in emotional well-being with weight is embedded within the central norepinephrine network.

Objective To investigate the influence of Yiqi Huatan Decoction (益气化痰方, YHD) on a model of depression in rats under different pathological conditions.

The brain noradrenaline (NA) and dopamine (DA) content of adult and developing mice of 3 age groups (3–5, 13–15 and 32–35 days) was assayed and found to increase with age. In adult mice 4 hrs after the administration of 50 mg/kg of amphetamine the brain NA content was decreased by 65 %. After 100 mg/kg of amphetamine the mice died in 25 min., but the NA and DA levels were only slightly decreased. In all age groups of developing mice, the doses of amphetamine sufficient to be lethal in 30 min. (100–160 mg/kg) caused only a slight decrease or even an increase in brain NA and DA levels. In developing mice surviving 60 min. after amphetamine, the brain amines were massively depleted. In adult mice the brain NA content in 1 hr and 4 hrs after the pretreatment dose of 5 mg/kg of amphetamine decreased by 20 %. The dose of 60 mg/kg 4 hrs after the pretreatment caused a massive depletion in brain NA and DA content 1 hr after the latter injection. Even though the mice survived. The lack of correlation between brain catecholamine depletion and amphetamine toxicity reflects the complex lethal mechanisms induced by the drug.

Endurance exercise is efficacious in reducing arterial stiffness. However, the effect of resistance training (RT) on arterial stiffening is controversial. High-intensity, high-volume RT has been shown to increase arterial stiffness in young adults. We tested the hypothesis that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume would not elicit increases in either central or peripheral arterial stiffness or alter aortic pressure wave reflection in young men and women. The RT group ( n = 24; 21 ± 1 years) performed two sets of 8–12 repetitions to volitional fatigue on seven exercise machines on 3 days/week for 12 weeks, whereas the control group ( n = 18; 22 ± 1 years) did not perform RT. Central and peripheral arterial pulse wave velocity (PWV), aortic pressure wave reflection (augmentation index; AIx), brachial flow–mediated dilation (FMD), and plasma levels of nitrate/nitrite (NOx) and norepinephrine (NE) were measured before and after RT. RT increased the one-repetition maximum for the chest press and the leg extension ( P < 0.001). RT also increased lean body mass ( P < 0.01) and reduced body fat (%; P < 0.01). However, RT did not affect carotid-radial, carotid-femoral, and femoral-distal PWV (8.4 ± 0.2 vs. 8.0 ± 0.2 m/sec; 6.5 ± 0.1 vs. 6.3 ± 0.2 m/sec; 9.5 ± 0.3 vs. 9.5 ± 0.3 m/sec, respectively) or AIx (2.5% ± 2.3% vs. 4.8% ± 1.8 %, respectively). Additionally, no changes were observed in brachial FMD, NOx, NE, or blood pressures. These results suggest that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume does not increase central or peripheral arterial stiffness or alter aortic pressure wave characteristics in young subjects.

The present study was undertaken to determine whether NO involved in the regulation of ovarian steroidogenesis in female rats. The purpose of the present study was to investigate whether NO might inhibits ovarian steroidogenesis. Female rats were divided of five rats including, receiving, N-omega-nitro-L-arginine methyle ester (L-NAME), an inhibitor of NO synthesis, Trinitroglycerin (TNG), an NO donor, L-arginine, normal saline. After 21 days, concenteration of progesterone and oesteradiol were measured by Electerochemiluminescence (ECL). Result showed that: TNG significantly decreased concentration of progesterone (50%) and L-NAME partially increased ovarian oesteradiol, but not differ effect from that rats treated with trinitroglycerin.

Previous studies found that elimination of the geomagnetic field (GMF) interferes with the normal brain functions, but the underlying mechanism remains unknown. The present study examined the effects of long-term exposures to a near-zero magnetic environment on the noradrenergic activities in the brainstem of golden hamsters. Both the content of norepinephrine (NE) and the density of NE-immunopositive neurons in the tissue decreased significantly after the treatment, and the effects could be progressive with time. These variations may substantially contribute to behavioral and mood disorders reported in other studies when animals are shielded from the GMF.

Background: Noradrenaline reuptake inhibitors are known to produce analgesia through a spinal action but they also act in the brain. However, the action of noradrenaline on supraspinal pain control regions is understudied. The authors addressed the noradrenergic modulation of the dorsal reticular nucleus (DRt), a medullary pronociceptive area, in the spared nerve injury (SNI) model of neuropathic pain. Methods: The expression of the phosphorylated cAMP response element-binding protein (pCREB), a marker of neuronal activation, was evaluated in the locus coeruleus and A5 noradrenergic neurons (n = 6 rats/group). pCREB was studied in noradrenergic DRt-projecting neurons retrogradely labeled in SNI animals (n = 3). In vivo microdialysis was used to measure noradrenaline release in the DRt on nociceptive stimulation or after DRt infusion of clonidine (n = 5 to 6 per group). Pharmacology, immunohistochemistry, and western blot were used to study α-adrenoreceptors in the DRt (n = 4 to 6 per group). Results: pCREB expression significantly increased in the locus coeruleus and A5 of SNI animals, and most noradrenergic DRt-projecting neurons expressed pCREB. In SNI animals, noradrenaline levels significantly increased on pinprick (mean ± SD, 126 ± 14%; P = 0.025 vs. baseline) and acetone stimulation (mean ± SD, 151 ± 12%; P < 0.001 vs. baseline), and clonidine infusion showed decreased α2-mediated inhibitory function. α1-adrenoreceptor blockade decreased nociceptive behavioral responses in SNI animals. α2-adrenoreceptor expression was not altered. Conclusions: Chronic pain induces brainstem noradrenergic activation that enhances descending facilitation from the DRt. This suggests that antidepressants inhibiting noradrenaline reuptake may enhance pain facilitation from the brain, counteracting their analgesic effects at the spinal cord.

Psychologists and neuroscientists have had a long-standing interest in the P3, a prominent component of the event-related brain potential. This review aims to integrate knowledge regarding the neural basis of the P3 and to elucidate its functional role in information processing. The authors review evidence suggesting that the P3 reflects phasic activity of the neuromodulatory locus coeruleus-norepinephrine (LC-NE) system. They discuss the P3 literature in the light of empirical findings and a recent theory regarding the information-processing function of the LC-NE phasic response. The theoretical framework emerging from this research synthesis suggests that the P3 reflects the response of the LC-NE system to the outcome of internal decision-making processes and the consequent effects of noradrenergic potentiation of information processing. Copyright 2005 by the American Psychological Association.

As mind sports becomes the new frontier for doping concerns, research is exploring whether users really get any value from 'smart drugs'.

That smooth muscles dilate and contract rhythmically has been known for a long time and the phenomenon has been studied for nearly as long. However, the causes and effects of smooth muscle oscillation (termed vasomotion) are far from clear. It is thought that vasomotion aids the delivery of oxygen to tissues surrounding capillary beds. On the other hand, unregulated vasomotion might participate in the development and maintenance of pathophysiological states. Nilsson and Aalkjaer review what is known about vasomotion and its consequences.

Stimulants are the most often prescribed psychotropics in children and adolescents, used generally for the treatment of attention deficit /hyperactivity disorder (ADHD). In this article the authors summarize the literature on prevalence of usage, neurobiology, and pharmacology of the stimulants. Recent studies on the use of stimulants in special ADHD populations including preschoolers and adults, and co-occuring neurologic, psychiatric, and substance use disorders are cited. Clinical guidelines for the management of individuals receiving the stimulants are offered, and treatment strategies delineated for ADHD subjects with comorbidity and medication-induced adverse effects are discussed.

Although the pivotal role played by the brain in the maintenance of optimal physiologic and psychologic health has long been recognized, methods for the direct examination of human central nervous system processes have only recently been developed. A growing body of evidence indicates that central nervous systemmonoaminergic cell groups, in particular those utilizing norepinephrine as their neurotransmitter, participate in the excitatory regulation of the sympathetic nervous system and the development of the hypertensive state.

It has been well-established that insulin-induced hypoglycemia evokes preferential adrenaline release from the adrenal medulla in fasted adult rats. The present study examined the responsiveness to hypoglycemia in fasted 21-day-old and 8-week-old rats. The recovery of adrenaline in the chromaffin granule fraction prepared from the 8-week-old rat adrenal homogenate decreased 30 min after subcutaneous injection of 3 U/kg insulin, whereas the recovery of both adrenaline and noradrenaline was diminished in 21-day-old rats. In electron microscopy, omega-shaped profiles, indicative of exocytosis, were frequently observed in adrenaline- and noradrenaline-storing cells of 21-day-old rats. These results indicate that the responsiveness of the noradrenaline-storing cells to hypoglycemia in 21-day-old rats is different from that in young adult rats.

The present study was designed to investigate the behavioral and neurochemical effects of long-term oral rutin administration to old male WAG rats (100 and 200 mg/kg b.w./day). Rutin is a well-known dietary flavonol glycoside with antioxidant and anti-inflammatory properties.First, spatial memory was assessed in the water maze and then the levels of neurotransmitters in selected brain regions were estimated.There was enhanced spatial memory in aged rats pretreated with the smaller dose of rutin in the probe trial of the water maze, nevertheless, augmented levels of noradrenaline in the hippocampi of these animals were not correlated with improved spatial memory. The increased dopamine levels in the hypothalami of the same group of animals may suggest effects other than behavioral.Long-term rutin pre-treatment may cause behavioral and neurochemical changes in aged WAG male rats.

In spontaneously hypertensive rats (SHR) arterial vasodilators do not cause regression and might cause further progression of cardiac hypertrophy. To assess whether these effects extend to the vasculature, and to examine the possible mechanisms involved, cardiac and mesenteric arterial structure was evaluated with respect to changes in cardiac volume load and cardiac and arterial sympathetic activity during long-term (5- and 10-week) treatment of 16-week-old SHR with the arterial vasodilator minoxidil, alone or in combination with the diuretic hydrochlorothiazide.Despite causing a persistent decrease in blood pressure in SHR, minoxidil further increased left and right ventricular weights and left ventricular internal diameter. In combination with hydrochlorothiazide, minoxidil caused concentric, rather than eccentric, left ventricular hypertrophy. In the mesenteric arterial bed of SHR, minoxidil increased the lumen of the superior mesenteric artery, and prevented further increases in the medial area of the large and small mesenteric arteries. The increase in lumen size of the superior mesenteric artery by minoxidil was abolished when hydrochlorothiazide was added to the treatment. After 10 weeks' treatment with minoxidil, noradrenaline turnover rates were still significantly increased in the left ventricle but were decreased in the mesenteric arteries in the SHR. Minoxidil increased plasma and blood volumes, the increases being largely prevented by concomitant diuretic treatment.We conclude that there are regional differences in the response of the cardiovascular system to minoxidil in SHR. Some of these differences may be related to differences in regional sympathetic activity, whereas volume load appears to play a modulatory role.

Streptozotocin-induced diabetes disrupts copulatory behavior in the male rat. The increase in serum luteinzing hormone (LH) that occurs in the male rat in response to the presence of a receptive female is absent in most diabetic rats. A female-induced testosterone rise is not seen in diabetic male rats, including those showing an increase in LH. The female-induced LH rise appears to be secondary to increased hypothalamic norepinephrine metabolism, which is severely attenuated in diabetic rats not exhibiting an LH rise in response to a female.

Dysfunction of the prefrontal cortex (PFC) is a hndamental component of attention-deficit/hyperactivity disorder (ADHD). The PFC uses working memory to intelligently guide behavior, inhibiting inappropriate impulses or distractions and allowing us to plan and organize effectively (see previous column). Individuals with ADHD are consistently impaired on tests of frontal lobe function, and both structural and functional imaging studies have shown evidence of altered PFC function in individuals with ADHD. In particular, the right PFC has been shown to be consistently smaller in

In an unselected group of thirty-eight depressed patients it was found that clinical recovery was positively correlated with an enhanced systolic blood pressure response to infused NE. All forms of physical treatment employed resulted in high recovery rates and high rates of NE potentiation as compared with a placebo group. Patients who showed a low (below the median) initial NE response showed higher recovery rates and higher rates of NE potentiation when given a somatic treatment than did patients with a high initial NE response.

Texto completo: acesso restrito. p. 79-87 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-09-10T16:40:52Z No. of bitstreams: 1 258690.pdf: 158054 bytes, checksum: 8afae736b0fc567cac496e4af42fd4cf (MD5) Approved for entry into archive by Patricia Barroso(pbarroso@ufba.br) on 2013-09-10T19:38:36Z (GMT) No. of bitstreams: 1 258690.pdf: 158054 bytes, checksum: 8afae736b0fc567cac496e4af42fd4cf (MD5) Made available in DSpace on 2013-09-10T19:38:36Z (GMT). No. of bitstreams: 1 258690.pdf: 158054 bytes, checksum: 8afae736b0fc567cac496e4af42fd4cf (MD5) Previous issue date: 2010 Background and Aims: Stress can alter many aspects of the immune response, and many studies have been conducted on the effects of stress on inflammatory processes, but little is known about its influence on the resolution of inflammation in tissue homeostasis, which includes the clearance of apoptotic cells by macrophages in a non-phlogistic way. In the present study, we investigated the effect of acute cold stress on the phagocytosis of apoptotic cells by macrophages. Methods: Mice were submitted to acute cold stress (4°C for 4 h) and the capacity of peritoneal macrophages to phagocyte apoptotic thymocytes and to secrete anti-inflammatory cytokines was evaluated. Plasma corticosterone and catecholamine levels were investigated to assess their effect on the phagocytic capacity of macrophages in vitro. Results: We showed that acute cold stress decreases phagocytosis of apoptotic cells at the inflammatory site by lipopolysaccharide-activated macrophages but did not affect resting macrophages. The inhibitory effect on phagocytosis is accompanied by a reduced level of TGF-β and higher IL-10 secretion. After stress, plasma concentrations of corticosterone increased 6-fold, epinephrine 2-fold and norepinephrine 1.7-fold compared to control mice. In vitro experiments showed that the decrease in phagocytosis after stress could be attributed, at least in part, to the effects of corticosterone; epinephrine and norepinephrine had no effect. Conclusions: The current study shows that acute cold stress decreases phagocytosis of apoptotic cells from an inflammatory environment by macrophages, and this inhibition is mediated by the intracellular glucocorticoid receptor.

Adrenal catecholamines (CA) were measured in 6-, 18-, and 30-mo Lobund-Wistar rats (LWR) maintained under germ-free or conventional conditions and fed either ad libitum or a restricted (70% of adult ad libitum) diet. Levels of dopamine (DA), norepinephrine (NE), epinephrine (E), and dihydroxymandelic acid (DHMA) were determined by HPLC-EC. Compared with values from 6- and 18-mo rats, mean adrenal weight, DA and NE content and concentration, and E content were increased in the 30-mo rats; E concentration was not. The ratio of E:NE declined in the 30-mo group. Germ-free status and dietary restriction had little effect in modulating these age-related changes. Reanalysis of adrenal weights of 30-mo rats revealed two clear subgroups, hyperplastic and non-hyperplastic; the data from hyperplastic adrenals revealed an exaggerated form of the "aged" CA profile, whereas data from the nonhyperplastic adrenals more closely resembled that of younger rats. Thus, aging in LWR is associated with adrenal hyperplasia and a tendency toward elevated adrenomedullary stores of DA and NE, while E stores are maintained near levels found in young rats.

This article reviews the neurobiologic rationale for and presents clinical guidance concerning the use of medications that reduce central nervous system noradrenergic activity in the treatment of intrusive symptoms of posttraumatic stress disorder. The authors reviewed neurobiological studies, nonclinical studies using animal models, clinical case reports, open-label drug studies, and blinded, placebo-controlled drug studies. This review of the basic science and clinical literature, and the authors' clinical experience with culturally and demographically diverse populations, indicate that clonidine and prazosin can play a useful role in treating sleep disturbance and hyperarousal in posttraumatic stress disorder, with minimal adverse effects and low financial cost.

The objectives of this study were to determine the effects of L-arginine-derived nitric oxide (NO) synthesis and noradrenergic function on skin electrical resistance of acupoints and meridians.Experiments were performed on male Sprague-Dawley rats anesthetized with sodium pentobarbital. Low skin-resistance points (LSRP; BL 56, PC 6, CV 17), non-LSRP positions (along the meridians), and non- LSRP, non-meridian control positions (adjacent to but not along the meridians) were determined on the skin surface by measurements of the skin stimulus-evoked electrical currents. The effects of L-arginine-derived NO synthesis and noradrenergic function on the currents, representing skin electrical resistance, were examined in the LSRP, non-LSRP, and non-meridian control points.The skin stimulus-evoked electrical currents at BL 56 (36.4 +/- 1.4 microA), PC 6 (35.4 +/- 1.2), and CV 17 (33.1 +/- 1.4) were significantly higher than those in non-LSRP and non-meridian control positions (p0.01, n = 7). The currents were consistently increased after repeated stimulation along the skin as a function of time. Intravenous injections of L-arginine (3 mg/kg, 10 mg/kg, and 30 mg/kg) and 3-morpholinyl-sydnoneimine (SIN-1; 1 microg/kg, 3 microg/kg, and 10 microg/kg) produced dose-dependent increases in the currents (p0.05, n = 5-6), but currents were not altered by injections of D-arginine (3 mg/kg, 10 mg/kg, and 30 mg/kg). Stimulus-evoked increases in currents were blocked by intravenous injections of either N (G)-propyl-L-arginine (NPLA, 3 mg/kg), N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), or guanethidine (3 mg/kg), a noradrenergic blockade.This is the first evidence showing that L-arginine-derived NO synthesis and noradrenergic transmission modify the skin electric conductance of LSRP. L-Arginine-derived NO synthesis appears to mediate noradrenergic function on skin sympathetic nerve activation, which contributes to low resistance characteristics of acupoints and meridians.

The serotonin (5-HT) system in the brain is a global modulator thought to tune up a unique subset of brain keynotes such as emotion, motivation, and sleep/conscious states in the deepest seats of cognition and behavior. In pursuit for coherent accounts of such higher-order issues, we have been trying to deduce the system dynamics of 5-HT in full span from the perturbation-response couples elicited by our most quick, specific. extensive, and reversible depletion of the brain 5-HT so far available via plasma precursor annihilation by injection of a tryptophan degrading enzyme (TSO) (ISTRY meetings-1986 in Cardiff, -92 in Nagoya and -98 in Hamburg). Herein discussed are the dynamics of the 5-HT depletion both in the whole brain and regional dimensions, and then the perturbation-induced manifestation of a continuous behavioral quiescence underlain by chaotic patterns of sleep/waking states. This response in sharp contrast to those by earlier serotonin depletors, prompts us to consider a serious revision of the current 5-HT scenario. In the light of our research, future directions will be discussed together with the RTD (rapid tryptophan depletion) claiming the impaired brain 5-HT turnover by a partial decline of plasma tryptophan.

Noradrenaline released during arousal controls the ability of astrocytes to respond to local neuronal activity.

Issue: α 2A -Adrenergic agonists hypothetically increase the strength of signals in prefrontal cortex (PFC), enhancing the efficiency of information processing at pyramidal neurons and resulting in the improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD), including oppositional symptoms.

Iodine-123 MIBG is a biochemical marker that can be used to monitor pulmonary norepinephrine (NE) metabolism. The purpose of this study was to characterize pulmonary I-123 MIBG kinetics in relation to age and gender.Seventeen healthy volunteers and 14 patients with no cardiac or pulmonary disorders were included in this study (age range: 24 to 88 years, mean age 50.2 +/- 17.6 years; 16 males, 15 females). Planar images were obtained 15 min (early) and 3 h (delayed) after injection of I-123 MIBG (111 MBq). Pulmonary uptake of I-123 MIBG was quantified based on the lung-to-mediastinum ratio (LMR) on early and delayed images. The lung clearance rate (LCR) was calculated form both the early and delayed images.Both early and delayed LMR values increased slightly, although they showed no significant correlations with age. There was a significant inverse correlation between LCR and age (r = -0.57, p0.001). Neither LCR nor LMR differed significantly between male and female patients, but the mean age of the men was lower than that of the women.Pulmonary I-123 MIBG kinetics may reflect age-dependent changes in NE metabolism. The effects of age should be taken into account when assessing pulmonary NE metabolism with I-123 MIBG.

Selye defined stress as the nonspecific response of the body to any demand. Stressors elicit both pituitary-adrenocortical and sympathoadrenomedullary responses. One can test Selye’s concept by comparing magnitudes of responses at different stress intensities and assuming that the magnitudes vary with stress intensity, with the prediction that, at different stress intensities, ratios of increments neuroendocrine responses should be the same. We measured arterial plasma ACTH, norepinephrine, and epinephrine in conscious rats after hemorrhage, intravenous insulin, subctaneous formaldehyde solution, cold, or immobilization. Relative to ACTH increments, cold evoked large norepinephrine responses, insulin large epinephrine responses, and hemorrhage small norepinephrine and epinephrine responses, whereas immobilization elicited large increases in levels of all three compounds. The ACTH response to 25% hemorrhage exceeded five times that to 10%, and the epinephrine response to 25% hemorrhage was two times that to 10%. The ACTH response to 4% formaldehyde solution was two times that to 1%, and the epinephrine response to 4% formaldehyde solution exceeded four times that to 1%. These results are inconsistent with Selye’s doctrine of nonspecificity and the existence of a unitary “stress syndrome,” and they are more consistent with the concept that each stressor has its own central neurochemical and peripheral neuroendocrine “signature.”