Brain Epinephrine Research Articles

An emerging role for microglia in stress-effects on memory.

Stressful experiences evoke, among others, a rapid increase in brain (nor)epinephrine (NE) levels and a slower increase in glucocorticoid hormones (GCs) in the brain. Microglia are key regulators of neuronal function and contain receptors for NE and GCs. These brain cells may therefore potentially be involved in modulating stress effects on neuronal function and learning and memory. In this review, we discuss that stress induces (1) an increase in microglial numbers as well as (2) a shift toward a pro‐inflammatory profile. These microglia have (3) impaired crosstalk with neurons and (4) disrupted glutamate signaling. Moreover, microglial immune responses after stress (5) alter the kynurenine pathway through metabolites that impair glutamatergic transmission. All these effects could be involved in the impairments in memory and in synaptic plasticity caused by (prolonged) stress, implicating microglia as a potential novel target in stress‐related memory impairments.

Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats.

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

What is the effect of body’s chemical messengers in the brain?

Neurochemical transmitters in the brain are fundamental to normal brain function and this investigation aims to introduce a study on the center of neuroscientific through an account of language development which conducts human speech mechanism using theoretical methods. In the process of this work, new understanding has been gained from the neurochemistry of several important neurotransmitters of dopamine (DA), epinephrine (EN), norepinephrine (NE), histamine (HA) and serotonin (ST) in brain by Monte Carlo simulation (MC) which uses the increased temperature to the potential energy of the neurochemicals in the brain considering the geometry optimization of the compounds as an additional conformational level. Moreover, the results of optimized DA, EN, NE, HA, ST neurochemical transmitters by running the physicochemical parameters as a practical model using Gaussian 09 program package can approve the twisting of language-brain due to these structures using density electron deliverers. The most stable of these compounds through the active sites of nitrogen and oxygen atoms has illustrated the best optimized position for localizing the structure through delivery technique in the brain to activate the center of learning a language as a simulated model. So, the best results with the calculated amounts conduct us to analyze the perspective of language learning process and enhancing this ability.

Susceptibility of mice strains to oxidative stress and neurotransmitter activity induced by Plasmodium berghei.

This study investigated the susceptibility of female C57Bl/6 and Swiss Albino mice to oxidative stress and neurotransmitters activity induced by Plasmodium berghei. On day 9 p.i. with P. berghei infected erythrocytes, the mice reduced in weight. This weight loss was markedly higher in SW mice and reached about −14%. Also, the infection was able to cause oxidative damage to the brain tissue. Catalase activity as well as glutathione, malondialdehyde and nitric oxide levels were different in the two mice strains. Moreover, the brain content of neurotransmitters, epinephrine, norepinephrine, dopamine and serotonin in mice brain was higher in SW mice than B6 mice. We concluded that, the strain of mice is one factor that could alter the response of mice to P. berghei infection.

Adiponectin is the most useful predictor for all-cause mortality and recurrence of acute coronary syndrome in patients with acute myocardial infarction

Aims: This study was designed to determine the most useful biomarker for prediction of all-cause mortality and recurrence of acute coronary syndrome (ACS) in patients with ST-segment elevation myocardial infarction Methods: This study included 254 patients who underwent primary percutaneous coronary intervention. Multiple biomarker levels, including adiponectin (APN), aldosterone, brain natriuretic peptide, epinephrine, blood glucose (BG), and C-reactive protein (CRP), were measured on the second day of admission. All patients were equally divided into tertile groups according to the biomarker levels. A Cox regression model was used to examine the prognostic impact of each biomarker. Results: During follow-up (median, 1096 days), 50 of the 254 patients died and 24 patients experienced recurrence of ACS. In the univariate analyses, death rates increased significantly with increasing levels of all biomarkers except those of BG. In the multivariate models, the highest tertile of APN and CRP levels were significant predictors of all-cause mortality (hazard ratios: APN, 5.02; p < 0.001; CRP, 3.43, p < 0.001). The rate of ACS recurrence was significantly associated with APN levels. However, the other biomarkers did not show relationships with ACS recurrence. Multivariate analyses adjusted for APN, age, body mass index, diabetes, hypertension, smoking, and dyslipidemia identified the median and highest tertile of APN levels as the only predictors of ACS recurrence (hazard ratios: median, 4.46, p = 0.024; highest, 6.63, p = 0.005). ![Figure][1] ACS-free survival estimate Conclusions: Among the established biomarkers related to patient prognosis, APN was the most useful predictor of all-cause mortality and ACS recurrence. [1]: pending:yes

Antidepressant-like effect of the extracted of Kai Xin San, a traditional Chinese herbal prescription, is explained by modulation of the central monoaminergic neurotransmitter system in mouse

Ethnopharmacological relevanceKai Xin San (KXS) is a traditional Chinese herbal prescription for the treatment of depression-like disorders, anxiety, and impairment in learning and memory, however, there is very little scientific data concerning the efficacy of this. Aim of the studyThe present study aimed to investigate the antidepressant potential of Kai Xin San and its possible mechanisms. Materials and methodsMouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of KXS. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis, akinesia and hypothermia and 5-HTP induced head-twitch response in mice. The contents of monoamine neurotransmitters including epinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) in mice brain were determined by Elisa. Spontaneous motor activities of mice and rotarod test were performed to find whether KXS has excitatory or inhibitory actions on the central nervous system. ResultsThe results showed that intragastric administration of KXS at 175, 350, 700, 1400mg/kg/day or fluoxetine at 28mg/kg/day for 3 days significantly reduced the duration of immobility in TST and FST, while it showed no effect on the spontaneous motor activity and rotarod performance in mice. However, the effect was not dose-dependent. The pre-treatment with KXS or fluoxetine for 3 days could elevate the contents of NE, 5-HT and DA in mice brain significantly. When the mice were treated with KXS (350mg/kg, p.o) or desipramine (30mg/kg, p.o) for 7 days, both of them could antagonize reserpine-induced ptosis, akinesia and hypothermia. The KXS (350mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20min when KXS at dosages of 175, 350, 700 and 1400mg/kg/day were performed per os (p.o.) during a 1-day, 3-day or 7-day period. ConclusionsOur results suggested that KXS exerts antidepressant-like effect. A possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role.

The Brain Epinephrine-&amp;#945;1-Adrenoceptor System in Behavioral Activation and Depression

Disabling behavioral inactivity is a prominent symptom of a number of psychiatric disorders, most notably, major depressive illness. The neurobiology of these inactive states is currently believed to involve alterations in central serotonergic, noradrenergic or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain α1-adrenoceptors stimulated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems and plays a critical role in behavioral activation and depression. The present review covers the evidence for this system and includes findings that brain α1-adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This “EPI-α1 system” may therefore represent a new target system for disabling inactivity.

Emerging evidence for a central epinephrine-innervated alpha 1-adrenergic system that regulates behavioral activation and is impaired in depression.

Currently, most basic and clinical research on depression is focused on either central serotonergic, noradrenergic, or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain alpha(1B)-adrenoceptors innervated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems in parallel and plays a critical role in depression. The present review covers the evidence for this system and includes findings that brain alpha(1)-adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This "EPI-alpha(1) system" may therefore represent a new target system for this disorder.

Role of epinephrine stimulation of CNS alpha1-adrenoceptors in motor activity in mice.

The role of brain epinephrine (EPI) in the regulation of motor activity and movement in mice was examined. Blockade of EPI synthesis with i.p. 2,3-dichloro-alpha-methylbenzylamine (DCMB) or LY134046 was found to produce marked behavioral inactivity which could be significantly reversed by intraventricular injection of EPI and by three other alpha(1)-adrenoceptor agonists, norepinephrine (NE), 6-fluoronorepinephrine (6FNE), and phenylephrine (PE), as well as by serotonin (5HT). EPI had the largest effect of these agonists and also was the only one that reversed nondrug-induced inactivity of mice in their home cages during the light phase. The effects of EPI were blocked by coinfusion of an alpha(1)-adrenoceptor antagonist (terazosin) but not of an alpha(2)-(atipamezole) or beta(1) (betaxolol)-blocker. The rank order of maximal behavioral responses to EPI, 6FNE, and PE in DCMB-treated mice was the same as the rank order of their maximal stimulation of hydrolysis of phosphatidylinositol at cloned alpha(1B)-adrenoceptors in cell culture. On the basis of the above findings and of the central distributions of adrenergic neurons and alpha(1)-adrenoceptors, the existence of a central EPI-innervated alpha(1)-adrenergic receptor system is postulated which serves to coexcite or enhance signaling in several monoaminergic brain regions involved in movement and motor activity.

Antagonism of Ethanol Intoxication in Rats by Inhibitors of Phenylethanolamine N‐Methyltransferase

The probable involvement of brain epinephrine in the expression of the acute sedative and intoxicating effects of ethanol and pentobarbital is demonstrated. Two selective inhibitors of phenylethanolamine N-methyltransferase (PNMT), LY134046 and LY78335, proved to be potent and long-lasting antagonists of ethanol intoxication in rats. Acute antagonism of pentobarbital-induced intoxication was observed with LY134046. The present results are compatible with a role for central epinephrine synthesis in ethanol and pentobarbital-induced sedation and intoxication in rats.

Effects of maternal phenylalanine or tyrosine hydroxylase inhibition on postnatal maturation of catecholamine and amino acid metabolism in rats.

AbstractEffects of the inhibition of maternal phenylalanine (Phe) or tyrosine (Tyr) hydroxylase on the postnatal maturation of catecholamine, thyroxine and amino acid metabolisms were examined in young rats. The intraperitoneal injections of 100 mg/kg p‐chlorophenylalanine three times during the second gestational week together with 0.2% Phe solution as drinking water produced marked reduction in birth weight, body weight gain, brain weight, cerebral Tyr hydroxylase activity, adrenal epinephrine, renal norepinephrine and free amino acids in plasma and brain as well as delayed maturation of thermoregulation in the offspring. In contrast, the administration of 100 mg/kg α‐methyl‐p‐tyrosine with 0.2% Tyr supplementation did not affect general growth, but only decreased cerebral Tyr hydroxylase and serum thyroxine level, while cerebral dopamine was increased. These results indicate that maternal Phe hydroxylase inhibition induces more severe growth failure including catecholamine and amino acid metabolism than Try hydroxylase inhibition in postnatal development.

Epinephrine in mammalian brain

1. 1. Epinephrine is widely distributed in brains of various species throughout phylogeny but maintains its localization to hypothalamus and brainstem/medulla in all species studied. 2. 2. A general decrease in brain epinephrine content is observed phylogenetically beyond fishes with wide variation within species. 3. 3. The cellular localization of epinephrine forming enzyme is dissociated from epinephrine stores in hypothalamus where epinephrine appears to be primarily a hormone. 4. 4. Three proposed functional pools of epinephrine are described. Synthesis of a hormonal pool and a second, perhaps nonfunctional, pool co-stored in noradrenergic terminals in the forebrain occurs extraneuronally and is probably inhibited acutely in the presence of high corticosteroids due to inhibition of uptake 2. Synthesis of epinephrine in the neuronal pool found primarily in the medulla may be enhanced due to increased PNMT activity in the presence of elevated corticosteroids. 5. 5. Phylogenetic and pharmacological data suggest that epinephrine may play an important role in tonic regulation of the level of arousal, reward and sensitivity to environmental stimuli in mammals.

NIH conference. Alcohol withdrawal and noradrenergic function.

Alcohol withdrawal syndrome is characterized by signs of overactivity of the sympathetic nervous system. Biochemical studies indicate that increased release of norepinephrine is associated with certain symptoms of alcohol withdrawal, and the severity of the withdrawal symptoms correlates positively with the amount of norepinephrine released. In the rat, the brain epinephrine concentration is reduced by alcohol, a phenomenon probably associated with both the intoxicating and rewarding effects of alcohol intake. Furthermore, intoxicating effects of alcohol can be reversed by inhibiting epinephrine synthesis in the rat brain. In this species, alcohol withdrawal is associated with profound depletion of epinephrine in the hypothalamus. When clonidine, a norepinephrine alpha-2-receptor agonist, was infused in alcoholics, these receptors were found to be subsensitive during alcohol withdrawal, and this subsensitivity may contribute to the syndrome. Repeated withdrawals may lead to "kindling" and thus further enhancement of noradrenergic overactivity. Pituitary responsiveness to corticotropin-releasing hormone, which is a central regulator of stress responses and increases the firing rate of brain noradrenergic neurons, is altered during alcohol withdrawal.

Comparison of ketamine, physical restraint, halothane and pentobarbital: Lack of influence on serotonergic measures in monkeys and rats

The consequences of the use of ketamine for immobilization have been examined on the concentration of whole blood serotonin, concentrations of neurotransmitters and metabolites in CSF and brain, and specific binding of ligands related to neurotransmitters in brain. Vervet monkeys ( Cercopithecus aethiops sabaeus) were examined under conditions which compared ketamine with physical restraint and with halothane. It was found that ketamine, used acutely in monkeys for restraint, had no influence on the concentration of serotonin in whole blood or the concentration of 5-hydroxyindoleacetic acid or homovanillic acid in the CSF. In rats, untreated animals were compared with those treated with ketamine alone, or in conjunction with pentobarbital. Treatment with ketamine had no influence on the specific binding of ketanserin, imipramine, prazosin or dihydroalprenolol in brain of rat, nor any influence on the concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, epinephrine, dopamine, or dihydroxyphenylacetic acid in brain. A moderately increased concentration of homovanillic acid was observed in several areas of the brain of the rat after ketamine alone or paired with pentobarbital.

High-performance liquid chromatography of biogenic amines and metabolites in brain, cerebrospinal fluid, urine and plasma

A method for high-performance liquid chromatographic separation and electrochemical detection of biogenic amines and metabolites in a variety of biological matrices is described. The method employs either homogenization, precipitation or dilution followed by direct injection of the samples and permits the chromatographic resolution of dopamine, norepinephrine, epinephrine, serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in brain; 3-methoxy-4-hydroxyphenylglycol, DOPAC, 5-HIAA and HVA in cerebrospinal fluid; 5-HIAA, HVA and 5-HT in plasma; and 5-HIAA and HVA in urine. Alterations in chromatographic conditions, voltammetry and in vivo pharmacological manipulations are employed to verify the identity of the putative neurotransmitter and metabolite peaks in the biological samples.

Release of endogenous brain epinephrine by the calcium ionophores X537A and A23187

The Ca 2+ ionophores X537A and A23187 produced dose-dependent release of endogenous epinephrine (Epi) as well as norepinephrine (NE) and dopamine (DA) from chopped rat hypothalamus and brainstem. The X537A-induced release of these catecholamines (CAs) was found to be Ca 2+-independent, whereas the A23187-induced release was Ca 2+-dependent. X537A and A23187 were approximately equipotent in causing the release of the hypothalamic Epi, NE and DA, but X537A was much more effective than A23187 in causing the maximal release. X537A, but not A23187, reduced the total endogenous CA content and increased the total 3,4-dihydroxyphenylacetic acid (DOPAC) content in the chopped hypothalamus. Ca 2+-independent release of Epi, NE and DA in the chopped hypothalamus was also observed with indirectly acting sympathomimetic amines (e.g. tyramine and amphetamine). Tyramine and amphetamine did not affect the total endogenous CA contents nor the total DOPAC content. These results suggest that X537A caused release of endogenous brain Epi, NE and DA by transporting thebiogenic amines across vesicular or intracellular storage sites. However, A23187 caused release of these CAs by exocytosis via transport of Ca 2+ into the neurons.

Effects of brain epinephrine depletion on thermoregulation, reflex bradycardia, and motor activity in rats

Two hours after i.p. administration of 2-cyclooctyl-2-hydroxyethylamine (CONH), 1-aminomethylcycloundecanol (CUNH), 2,3-dichloro-α-methylbenzylamine (DCMB), or 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF64139), the hypothalamic and brain stem epinephrine (EPI) contents of rat brain were decreased. Depletions of brain EPI with these phenylethanolamine N-methyltransferase (PNMT) inhibitors reduced the rectal temperatures of rats at ambient temperatures of 8 and 22°C. The hypothermia in response to these PNMT inhibitors was due to decreased metabolism and cutaneous vasodilatation. The locomotor stimulant responses induced by thyrotropin-releasing hormone were also reduced by administration of any one of these PNMT inhibitors. On the other hand, acute administration of any of these PNMT inhibitors enhanced the reflex bradycardia induced by i.v. infusion of EPI. The data suggest that brain (particularly the hypothalamus and brain stem) EPI-containing neurons are involved in the regulation of body temperature, reflex bradycardia, and motor performance in the rat.

Decreasing brain epinephrine levels with 2-cyclooctyl-2-hydroxyethylamine induces hyperglycemia in rats.

Intraperitoneal administration of 2-cyclooctyl-2-hydroxyethyl-amine (CONH; 25-75 mg/kg) produced dose-related reductions in the epinephrine (EPI) concentrations in both the hypothalamic and brainstem regions, but not in the adrenal glands. The reductions in the hypothalamic and brainstem EPI concentrations in rats anesthetized with pentobarbital sodium were accompanied by parallel increases in blood glucose. These data suggest that CONH induces its hyperglycemia action at least in part by altering central EPI biosynthesis. This hyperglycemic was antagonized by spinal transection or adrenalectomy, but not by vagotomy. This indicates that CONH increases the adrenal-sympathetic efferent activity and leads to hyperglycemia in rats.

Brain epinephrine systems: detailed comparison of adrenergic and noradrenergic metabolism, receptor number and in vitro regulation, in two inbred rat strains

Epinephrine content and PNMT activity in medulla pons and hypothalamus of F344 inbred rats is from 3- to 8-fold higher than that of Buf inbred rats. These strain-dependent differences in brain adrenergic neurons are reciprocally related to altered α 1- and α 2-adrenergic receptor density in PNMT-containing brain regions. Radioligand binding indices related to α 2-receptor function reveal that receptors may be ‘desensitized’ as well as ‘down-regulated’ in the strain with high PNMT activity (F344), and may be ‘supersensitive’ as well as ‘up-regulated’ in the strain with low PNMT activity (Buf). The association between epinephrine-containing neurons and α-adrenergic receptor regulation appears specific, since α-adrenergic receptor density and regulation in brain regions devoid of PNMT and epinephrine is similar in F344 and Buf rats. While noradrenergic metabolism in F344 rats is greater than that in Buf rats, this difference is generalized throughout the brain and, thus, bears no apparent relationship to the localized alterations in α-adrenergic receptor density. Moreover, ß-adrenergic receptor density in the 2 strains is similar in all brain regions. These data suggest that a significant proportion of α-adrenergic receptors in medulla-pons and hypothalamus are intimately related to and regulated by epinephrine-containing nerve endings.

Effects of blinding and pinealectomy on regional brain monoamine concentrations.

The effects of blinding with or without pineal ablation on brain monoamine levels were studied in male rats. Brain dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT) were measured by radioenzymatic assays. Four weeks following pinealectomy, E levels were significantly enhanced in the frontal cortex. Chronic blinding decreased striatal DA levels and increased striatal 5-HT levels in both sham-operated and pinealectomized (Px) animals. In a second experiment Px animals were sacrificed 1 or 7 d after pinealectomy in order to examine the short-term effects of pinealectomy. There were no differences between controls and Px animals in their cortical levels of DA, NE, and E and their hippocampal and hypothalamic 5-HT levels. However, the E concentrations measured 1 d after surgery were significantly greater than after 7 d. The implications of these findings with regard to the reported role of the pineal and melatonin in brain homeostasis and endocrine regulation are discussed.