bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of Brain Stem Groups of Catecholaminergic Cells in Tumor‐Bearing Rats
Authors: Pirnik Zdenko , Bundzikova Jana , Bizik Jozef , Hulin Ivan , Kiss Alexander , Mravec Boris
Published: November 2009

The aim of the present study was to investigate the activity of tyrosine hydroxylase (TH) immunopositive neurons, measured by Fos protein expression, in the hindbrain noradrenergic (NA) cell groups in animals exposed to visceral tumor growth for 28 days induced by intraperitoneal implantation of fibrosarcoma cells. We were also interested in determining whether brain stem NA neurons of tumor‐bearing and intact animals exhibit similarities in their response to a strong heterotypic stimulus—immobilization (IMO) stress. We found increased Fos expression in NA cells of the nucleus tractus solitarii (A2 cell group) and of the A1 cell group of tumor‐bearing rats. However, Fos expression in other brain stem NA cell groups, including A5, locus ceruleus, and A7, were similar to control rats. The effect of 60 min of IMO was evident in both groups, but there were no differences between Fos expression in brain stem NA cell groups in control and tumor‐bearing rats. This indicates that the sensitivity of NA cells in tumor‐bearing animals was not altered by the IMO‐induced stress challenge. However, whether the increased Fos expression in NA cells in tumor‐bearing animals is a consequence of a specific visceral response activated by cancer development or just a nonspecific event accompanying the cancer progression requires further study.
Investigating the Molecular Basis of Major Depressive Disorder Etiology
Authors: Jabbi Mbemba , Korf Jaap , Ormel Johan , Kema Ido P. , Den Boer Johan A.
Published: November 2009

Genes play a major role in behavioral adaptation to challenging environmental stimuli, but the complexity of their contribution remains unclear. There is growing evidence linking disease phenotypes with genes on the one hand, and the genesis of stress‐related disorders like major depression, as a result of exposure to stressful environmental pathogens on the other. Here we illustrate the convergent role of monoaminergic genes in regulating the underlying biological mechanisms of stress and the emotions. By reviewing data that support a role of monoaminergic and other related genes in environmental adaptation, we conclude by advocating the use of convergent approaches in examining the genetic modulation of disease phenotypes.
Ethanol and Stress Activate Catecholamine Synthesis in the Adrenal
Authors: Patterson‐Buckendahl Patricia , Pohorecky Larissa A. , Kubovcakova Lucia , Krizanova Olga , Martin R. Bruce , Martinez Daniel A. , Kvetňanský Richard
Published: November 2009

Ethanol consumption and mental stress activate the sympathetic nervous system, which can adversely affect bone. We compared six groups of 10 young adult rats, three with and three without 2 h daily restraint stress. Two groups consumed food and waterad libitum, two received food and 6% (w/v) ethanol as drinking water, and two received the amount of food consumed by ethanol rats the previous day plus waterad libitum(pairfed). After 6 weeks, rats were killed. Plasma, femurs, lumbar vertebrae, and adrenals were harvested. Femoral dimensions were measured and biomechanical properties were tested by three‐point bending. Plasma osteocalcin, vertebral osteocalcin mRNA levels, and adrenomedullary tyrosine hydroxylase (TH), dopamine beta‐hydroxylase (DBH), and phenylethanolamine N‐methyl transferase (PNMT) mRNA levels were quantified. Daily restraint decreased weight gain and femoral length compared to dietary controls, and appeared to partially preserve bone strength, especially in calorie‐restricted pairfed rats. Femoral strength was significantly affected by treatment in that bones of pairfed controls were weakest, ethanol drinkers were intermediate, andad libitumrestrained were strongest. Femoral yield load, displacement, and work at yield load were negatively correlated with TH and DBH mRNA levels, but not PNMT, suggesting a negative influence of norepinephrine. Plasma osteocalcin and dry weight of lumbar 3–5 vertebrae were unaffected; however, osteocalcin mRNA in second lumbar vertebrae was positively correlated with TH, DBH, and PNMT levels. Ethanol consumption at this level had little effect on femur morphology or strength. In contrast, the data suggested possible stimulation rather than inhibition of vertebral bone formation.
Effects of Acute and Chronic Stressors and CRF in Rat and Mouse Tests for Depression
Authors: Dunn Adrian J. , Swiergiel Artur H.
Published: November 2009

Depressive illness is frequently associated with life stress. Corticotropin‐releasing factor (CRF) is believed to be a key brain mediator of behaviors associated with stress, and abnormalities in the function of CRF have been associated with depression. Therefore, we have studied the effects of acute and chronic footshock and restraint in tests used in rodents to assess depression‐like activity and antidepressant effects: the forced swim test in rats and mice, and the tail suspension test in mice. We also tested the effect of intracerebroventricular (icv) CRF administration. The results were complex. In the forced swim test in rats, acute footshock and restraint reduced floating, whereas chronic footshock increased floating as did icv CRF. However, chronic restraint induced opposite effects, decreasing floating in the forced swim test. The results from mice were significantly different. In the forced swim test, acute footshock and restraint decreased floating, while chronic footshock increased floating, and chronic restraint decreased floating as it did in rats. However, icv CRF decreased floating. The results from the tail‐suspension test paralleled those from the forced swim test except that chronic footshock tended to decrease the time spent immobile. Thus in rats, the behavioral effects of the chronic footshock in the forced swim test could be explained by a desensitization of the CRF systems, either decreased activation of CRF, or desensitization of its receptors. However, such an effect cannot explain the responses to restraint, nor the behavioral effects of chronic footshock and restraint in mice.
Type 1 and 2 IP3 Receptors Respond Differently to Catecholamines and Stress
Authors: Krizanova Olga , Holotnakova Tereza , Jurkovicova Dana , Polakova Eva , Zahradnikova Alexandra , Lacinova Lubica , Kvetňanský Richard , Myslivecek Jaromir , Pastorekova Silvia
Published: November 2009

Type 1 and 2 inositol 1,4,5‐trisphosphate (IP3) receptors have been found in cardiac tissue, although they are localized in different types of cells. While the type 1 predominates in neuronal cells and cardiac ganglia, type 2 IP3 receptor is localized mainly in cardiomyocytes. In the heart, gene expression of the type 1 IP3 receptor is modulated by catecholamines, while type 2 is not affected. In this study we compared the effects of two stressors—cold exposure and hypoxia—on gene expression and protein levels of type 1 and 2 IP3 receptors. We found that both types of IP3 receptors were increased by these stressors, although the response of the type 2 IP3 receptor was delayed. We propose that regulation of these types of IP3 receptors in the heart might differ in control conditions and during stress.
Sympathetic Nervous System Response to Orthostatic Stress in Female Patients with Rheumatoid Arthritis
Authors: Vlcek Miroslav , Rovensky Jozef , Blazicek Pavel , Radikova Zofia , Penesova Adela , Kerlik Jana , Kvetňanský Richard , Imrich Richard
Published: November 2009

Sympathoneural and adrenomedullary impairments have been suggested in patients with rheumatoid arthritis (RA). In the present study, sympathoneural and adrenomedullary responses to orthostasis were evaluated in eight female RA patients and in eight matched healthy controls. The testing consisted of sequence of stabilization period in supine position, legs‐up position, orthostasis, and supine position. In each body position, blood samples were drawn and ECG was recorded. Plasma levels of epinephrine (EPI), norepinephrine (NE) and neuropeptide Y (NPY) were measured and sympathoneural activity was evaluated by analysis of heart rate variability (HRV). Higher baseline NE levels were found in RA patients (P= 0.034), without any difference in response to orthostasis between the study groups. Levels of EPI tended to be lower in RA patients in base line (P= 0.053) and in response to orthostasis (P= 0.079). The RA and control groups did not differ in NPY levels or in HRV parameters considered to reflect sympathetic activity. A subtle tendency to decreased adrenomedullary reactivity but no evidence for abnormal sympathetic responses to orthostasis was found in RA females.
Adrenocortical Response to Low‐dose ACTH Test in Female Patients with Rheumatoid Arthritis
Authors: Radikova Zofia , Rovensky Jozef , Vlcek Miroslav , Penesova Adela , Kerlik Jana , Vigas Milan , Imrich Richard
Published: November 2009

Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 ± 2 years, BMI 21.0 ± 0.7 kg/m2) and 10 matched healthy controls (C: age 31 ± 1 years, BMI 21.6 ± 0.6 kg/m2). Low‐dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 μg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17‐OH‐progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 ± 38 versus C: 229 ± 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Δmax: 284 ± 24 in RA versus 424 ± 31 nmol/L in C, P= 0.002). ACTH‐induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Δmax: 2.59 ± 0.68 in RA versus 5.57 ± 1.25 ng/mL in C, P= 0.015). No significant between‐groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level.
Neuroendocrine Activation during Combined Mental and Physical Stress in Women Depends on Trait Anxiety and the Phase of the Menstrual Cycle
Authors: Hlavacova Natasa , Wawruch Martin , Tisonova Jana , Jezova Daniela
Published: November 2009

The aim of this study was to investigate the influence of trait anxiety and menstrual cycle phase on neuroendocrine activation during combined mental and physical stress procedure in 40 healthy female subjects. Women at the upper (anxious) and lower (nonanxious) limits of the normal range of a trait anxiety scale were exposed to the stress procedure consisting of a mental component (Stroop test) and handgrip exercise. Salivary cortisol levels, cardiovascular parameters, and cognitive performance in the Stroop test were evaluated. Stress‐induced cortisol levels and the rise in systolic blood pressure were affected by both trait anxiety and menstrual cycle phase. The stress model used induced a significant cortisol elevation only in anxious women in the follicular phase. This group of women also exhibited greater increases in systolic blood pressure in response to handgrip exercise as compared to anxious ones in the luteal phase and to nonanxious women in either phase. In nonanxious women, stress‐induced cortisol levels positively correlated with cognitive performance. In contrast, a negative correlation trend was observed in anxious subjects. Thus, in subjects with low but not high trait anxiety, enhanced cortisol concentrations seem to be associated with better cognitive performance. The results suggest that women with high trait anxiety exhibit greater cardiovascular and hormonal sensitivity to stress stimuli during the follicular phase.
Phenylethanolamine N‐Methyltransferase Gene Expression in the Heart and Blood Pressure Response to Oxytocin Treatment in Rats Exposed to Voluntary Wheel Running
Authors: Bakos Jan , Bobryshev Peter , Tillinger Andrej , Kvetňanský Richard , Jezova Daniela
Published: November 2009

This study aimed to contribute to the knowledge of cardiovascular regulation associated with repeated exercise by evaluating untraditional parameters in the model of voluntary wheel running. Possible changes in cardiac phenylethanolamine N‐methyltransferase (PNMT) gene expression were evaluated using running for 3 weeks in four rat strains, and the hypothesis that voluntary wheel running modifies mean arterial pressure (MAP) responses to oxytocin administration was verified. Running activity increased gradually and was high in spontaneously hypertensive rats (SHR) and Sprague‐Dawley rats, while low in Wistar rats. The levels of PNMT mRNA in the left but not right atrium increased significantly in rat strains exhibiting high physical activity. Concentrations of PNMT mRNA were significantly higher in SHR and Sprague‐Dawley compared to those in Wistar rats, which ran much shorter distances. MAP was found to be higher in rats exposed to voluntary running, which might be the result of the cessation of the exercise 24 h before the measurements. Oxytocin treatment (5 μg/kg and 30 μg/kg i.v.) resulted in significant increase in MAP in both control and running animals in a dose‐dependent manner. In conclusion, voluntary wheel running failed to modify sensitivity to cardiovascular action of oxytocin but resulted in increased gene expression of PNMT in left, but not right, heart atrium in a running activity–dependent manner.
Hypoxia Differently Modulates Gene Expression of Inositol 1,4,5‐Trisphosphate Receptors in Mouse Kidney and HEK 293 Cell Line
Authors: Jurkovicova Dana , Sedlakova Barbora , Lacinova Lubica , Kopacek Juraj , Sulova Zdena , Sedlak Jan , Krizanova Olga
Published: November 2009

Hypoxia is a state of insufficient oxygen supply of the tissue or cell. Kidney tissue is highly sensitive to oxygen deprivation and easily develops renal ischemic injury. Calcium transporters very sensitively react to oxygen deficiency. We investigated whether hypoxia affects the gene expression of intracellular calcium transporters in the intact kidney, and we compared the response to that of HEK 293 cells. Our results showed that, while in mouse kidney tissue hypoxia elevates mRNA for inositol 1,4,5‐trisphosphate receptors (IP3R) type 1 (IP3R1) and ryanodine receptors (RyR) type 2 (RyR2), in culture of HEK 293 cells the gene expression of all IP3Rs decreased without affecting viability of the cells. RyR2 mRNA in HEK 293 cells was not significantly changed, but RyR1 gene expression was significantly increased by hypoxia. The different response of kidney tissue and HEK 293 cells to hypoxia could be due to unequal differentiation state of the cells in intact tissue and cultured embryonic cell line. The physiological relevance of this observation remains to be determined.
Chronic Stress, Combined with a High‐Fat/High‐Sugar Diet, Shifts Sympathetic Signaling toward Neuropeptide Y and Leads to Obesity and the Metabolic Syndrome
Authors: Kuo Lydia E. , Czarnecka Magdalena , Kitlinska Joanna B. , Tilan Jason U. , Kvetňanský Richard , Zukowska Zofia
Published: November 2009

In response to stress, some people lose while others gain weight. This is believed to be due to either increased β‐adrenergic activation, the body's main fat‐burning mechanism, or increased intake of sugar‐ and fat‐rich “comfort foods.” A high‐fat, high‐sugar (HFS) diet alone, however, cannot account for the epidemic of obesity, and chronic stress alone tends to lower adiposity in mice. Here we discuss how chronic stress, when combined with an HFS diet, leads to abdominal obesity by releasing a sympathetic neurotransmitter, neuropeptide Y (NPY), directly into the adipose tissue. In vitro, when “stressed” with dexamethasone, sympathetic neurons shift toward expressing more NPY, which stimulates endothelial cell (angiogenesis) and preadipocyte proliferation, differentiation, and lipid‐filling (adipogenesis) by activating the same NPY‐Y2 receptors (Y2Rs). In vivo, chronic stress, consisting of cold water or aggression in HFS‐fed mice, stimulates the release of NPY and the expression of Y2Rs in visceral fat, increasing its growth by 50% in 2 weeks. After 3 months, this results in metabolic syndrome‐like symptoms with abdominal obesity, inflammation, hyperlipidemia, hyperinsulinemia, glucose intolerance, hepatic steatosis, and hypertension. Remarkably, local intra‐fat Y2R inhibition pharmacologically or via adenoviral Y2R knock‐down reverses or prevents fat accumulation and metabolic complications. These studies demonstrated for the first time that chronic stress, via the NPY‐Y2R pathway, amplifies and accelerates diet‐induced obesity and the metabolic syndrome. Our findings also suggest the use of local administration of Y2R antagonists for treatment of obesity and NPY‐Y2 agonists for fat augmentation in other clinical applications.
The Role of Norepinephrine and Insulin Resistance in an Early Stage of Hypertension
Authors: Penesova Adela , Radikova Zofia , Cizmarova Eva , Kvetňanský Richard , Blazicek Pavel , Vlcek Miroslav , Koska Juraj , Vigas Milan
Published: November 2009

The interrelationship between activity of sympathetic nervous system and metabolic risk factors in youth with hypertension (HT) has been poorly studied. The aim of our present study was to assess the interrelationship between metabolic risk factors, such as insulin resistance, concentration of plasminogen activator inhibitor (PAI)‐1, and catecholamines in an early stage of HT onset. An oral glucose tolerance test was performed in 17 young males with early‐diagnosed nontreated HT grade 1 and 16 gender‐, age‐, and BMI‐matched normotensive controls. Concentrations of glucose, insulin, epinephrine, norepinephrine, PAI‐1, and plasma renin activity (PRA) were determined in venous plasma. Insulin sensitivity indices (ISIs) proposed by Cederholm, Matsuda, and Gutt were calculated. HT had higher baseline levels of norepinephrine, insulin (P= 0.02), and PAI‐1 (P= 0.04). ISIs were lower in HT subjects (P < 0.001). Baseline concentrations of epinephrine were negatively associated with HDL cholesterol (r=−0.415, P= 0.02), ISI Matsuda (r=−0.361, P= 0.04), ISI Cederholm (r=−0.354, P= 0.04), and ISI Gutt (r=−0.429, P= 0.01), and positively with PRA (r= 0.609, P < 0.0001). Positive association was found between baseline concentrations of norepinephrine and PAI‐1 (r= 0.418, P= 0.02). The sympathetic overactivity, which occurs in the early stage of HT may contribute to reduced insulin sensitivity even in young patients and intensify the undesirable development of metabolic cardiovascular risk factors and progress of the disease.
Vasopressin Does Not Mediate Hypersensitivity of the Hypothalamic Pituitary Adrenal Axis during Chronic Stress
Authors: Chen Jun , Young Sharla , Subburaju Sivan , Sheppard Jack , Kiss Alexander , Atkinson Helen , Wood Susan , Lightman Stafford , Gal Claudine Serradeil‐Le , Aguilera Greti
Published: November 2009

The hypothesis that vasopressin (VP) becomes the main mediator of pituitary corticotroph responsiveness during chronic hypothalamic pituitary adrenal (HPA) axis activation was tested by examining the effect of pharmacologic VP receptor blockade on the adrenocorticotropic hormone (ACTH) and corticosterone responses of 14‐day repeatedly restrained rats. In spite of the increased vasopressinergic activity, repeatedly restrained rats showed lower ACTH and corticosterone responses to 10 min white noise compared with handled controls. These responses were unchanged by injection of the nonpeptide‐selective V1b receptor antagonist SSR149415 i.v., 1 h before noise application. In contrast to noise stress, plasma ACTH responses to i.p. hypertonic saline injection were enhanced in the repeatedly restrained rats compared with handled controls, but responses were also unaffected by SSR149415 administered orally, daily 1 h before restraint. Since SSR149415 effectiveness was low, we used minipump infusion of the peptide V1 receptor antagonist, dGly[Phaa1,D‐tyr(et), Lys, Arg]VP (V1‐Ant) for 14 days, which effectively blocked ACTH responses to exogenous VP. Chronic V1‐Ant infusion reduced plasma ACTH responses to i.p. hypertonic saline in handled controls but not in repeatedly restrained rats. These data suggest that the increased vasopressinergic activity characteristic of chronic stress plays roles other than mediating the hypersensitivity of the HPA axis to a novel stress.
Exposure to Severe Stressors Causes Long‐lasting Dysregulation of Resting and Stress‐induced Activation of the Hypothalamic‐Pituitary‐Adrenal Axis
Authors: Belda Xavier , Rotllant David , Fuentes Silvia , Delgado Raúl , Nadal Roser , Armario Antonio
Published: November 2009

Exposure to some predominantly emotional (electric shock) and systemic (interleukin‐1β) stressors has been found to induce long‐term sensitization of the hypothalamic‐pituitary‐adrenal (HPA) responsiveness to further superimposed stressors. Since exposure to immobilization on wooden boards (IMO) is a severe stressor and may have interest regarding putative animal models of post‐traumatic stress disorders (PTSD), we have characterized long‐lasting effects of a single exposure to IMO and other stressors on the HPA response to the same (homotypic) and to novel (heterotypic) stressors and the putative mechanisms involved. A single exposure to IMO caused a long‐lasting reduction of peripheral and central responses of the HPA axis, likely to be mediated by some brain areas, such as the lateral septum and the medial amygdala. This desensitization is not explained by changes in negative glucocorticoid feedback, and, surprisingly, it is positively related to the intensity of the stressors. In contrast, the HPA response to heterotypic stressors (novel environments) was enhanced, with maximal sensitization on the day after IMO. Sensitization progressively vanished over the course of 1–2 weeks and was not modulated by IMO‐induced corticosterone release. Moreover, it could not be explained by changes in the sensitivity of the HPA axis to fast or intermediate/delayed negative feedback, as evaluated 1 week after exposure to IMO, using shock as the heterotypic stressor. Long‐lasting stress‐induced behavioral changes reminiscent of enhanced anxiety and HPA sensitization are likely to be parallel but partially independent phenomena, the former being apparently not related to the intensity of stressors.
Effects of Estrogen on Stress‐induced Activation of Peptide Neurons in PVN of Ovariectomized Rats
Authors: Hara Yasuko , Kohno Tomomi , Takamata Akira , Ueyama Takashi , Morimoto Keiko
Published: November 2009

Estrogen has been implicated in brain function related to stress responses. We investigated whether estrogen affects psychological stress‐induced activation of peptide‐containing or nitric oxide–producing neurons in the paraventricular hypothalamic nucleus (PVN) in ovariectomized (OVX) rats, both placebo‐treated (OVX + Pla) and estrogen‐treated (OVX + E2) by comparison of c‐Fos expression using immunohistochemistry. Cage‐switch stress increased activation in oxytocinergic neurons in the parvocellular PVN (pPVN) in OVX + Pla, but not in that of OVX + E2, rats. Moreover, the stress‐induced activation in NADPH‐diaphorase‐positive neurons in the pPVN was larger in the OVX + E2 than in the OVX + Pla group. These findings suggest that estrogen attenuates the activation of oxytocinergic neurons in the pPVN, at least in part via nitric oxide.
GABA Regulates the Rat Hypothalamic‐Pituitary‐Adrenocortical Axis via Different GABA‐A Receptor α‐Subtypes
Authors: Mikkelsen Jens D. , Bundzikova Jana , Larsen Marianne H. , Hansen Henrik H. , Kiss Alexander
Published: November 2009

The control of the corticotropin‐releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) is balanced by excitatory and inhibitory inputs. The GABA‐A receptor, which is a major target for the inhibitory control, is composed of five subunits. The presence of an α1‐, α2‐, α3‐, or α5‐subunit in the GABA‐A receptor protein complex is necessary for benzodiazepines to exert their potentiating effect on the receptor. We postulate that the effect of nonselective benzodiazepines on the hypothalamo‐pituitary adrenocortical (HPA) axis is critically dependent on the composition of the GABA‐A receptor subunits through which they act. We show here that positive modulators of α1‐subtype containing GABA‐A receptors with zolpidem (10 mg/kg) increase HPA activity in terms of increase in plasma corticosterone and induction of Fos in the PVN, whereas activation of non‐α1‐subtype GABA‐A receptors using L‐818,417 (10 mg/kg) likely inhibits the activity. We also show that the α2‐subunit gene is highly expressed in the PVN, but its expression is not affected by chronic mild stress. These results show that the stimulatory effect on HPA activity after positive modulation of GABA‐A receptors composed of α1‐subunit(s) affects a selective afferent system than the PVN, which is distinct from another afferent system(s) activated by non α1‐containing GABA‐A receptors.
Changes in c‐Fos and NOS Expression in the PVH of Lactating Rats in Response to Excitotoxicity and Stress
Authors: Monasterio Nela , Ramos Eugenia , Morales Teresa
Published: November 2009

This study investigated how lactation modified the expression patterns of Fos and nitric oxide synthase in the hypothalamic paraventricular nucleus (PVH) induced by excitotoxicity and stress. Kainic acid or egg white treatment weakly activated Fos expression in the PVH of lactating in comparison to diestrus or ovariectomized (OVX) rats. Labels for NADPH‐diaphorase and nNOS revealed a different distribution pattern in the PVH depending on the physiological condition and challenge. The present results confirm that lactation attenuates the PVH activational response to stress and excitotoxicity, and both stimuli induced nitric oxide expression in the PVH of diestrus, lactating, and OVX rats.
Endocrine Factors in Stress and Psychiatric Disorders
Authors: Jezova Daniela , Hlavacova Natasa
Published: November 2009

Glucocorticoids and other steroids produced in the adrenal cortex are altered in chronic stress situations associated with enhanced anxiety. A useful tool to evaluate changes in adrenal steroids during stress and anxiety under both laboratory and real‐life stress situations is determination of steroids in saliva. The main advantages of this technique are its noninvasiveness and its measurement of biologically active free hormone levels. Salivary cortisol is a valuable indicator of the activity of the hypothalamic‐pituitary‐adrenocortical axis, which is known to be altered in psychiatric disorders. Measurements of salivary cortisol helped to reveal changes that would otherwise remained undetected, such as increase in cortisol release in spontaneously occurring panic attacks. By selecting only the subjects with high and low trait anxiety, we have brought evidence confirmed by others that high trait anxiety may be associated with an inability to respond with adequate cortisol release during stress. Papers on the relationship between salivary dehydroepiandrosterone and trait anxiety or anxiety disorders are rare, and this stress hormone deserves more attention. Almost nothing is known on aldosterone and anxiety. We have modified the methodology of aldosterone radioimmunoassay by concentrating the saliva and validated it biologically by demonstrating daily variation and gender differences. We have provided the first data on the relationship between aldosterone and trait anxiety. Obtained results show a significant negative correlation between morning salivary aldosterone concentrations and trait anxiety scores in women (luteal phase), but not in men. A more proper elucidation of the association between aldosterone and anxiety seems to be an important target of further research.
Impaired Chronotropic Response to Exercise in Mice Lacking Catecholamines in Adrenergic Cells
Authors: Bao Xuping , Liu Fujun , Gu Yusu , Lu Chuanyi M. , Ziegler Michael G.
Published: November 2009

To define the in vivo role of adrenergic catecholamines (CAs), we generated a mouse model whereby tyrosine hydroxylase (TH) was knocked out (KO) in phenylethanolamine N‐methyltransferase–expressing cells. These adrenergic specific TH‐KO mice were viable and grossly normal. Their resting heart rate and blood pressure, as monitored by telemetry, were unchanged. However, when challenged with treadmill exercise, their chronotropic responses were significantly reduced by 14% compared to wild‐type mice. Thus, our data suggest that adrenergic CA is required for normal chronotropic responses to stress, but not required for prenatal and postnatal development or normal cardiovascular function at rest.
Neonatal Programming of Rat Behavior by Downregulation of Alpha2A‐Adrenoreceptor Gene Expression in the Brain
Authors: Dygalo Nikolay N. , Kalinina Tatyana S. , Shishkina Galina T.
Published: November 2009

Short‐term knockdown of alpha2A‐adrenergic receptor gene expression in the rat brain by siRNA or antisense oligodeoxynucleotide during the first days of life induced acute and long‐lasting neurochemical and behavioral alterations. The acute effects in the neonatal rats were consistent with the known functions of the alpha2A‐adrenergic receptors in the mature animals. The long‐lasting alterations suggested involvement of receptor‐specific gene expression during the critical period of brain development in early‐life programming of anxiety‐related behavior.
Salivary Cortisol Levels in Brazilian Citizens of Distinct Socioeconomic and Cultural Levels
Authors: Garcia Márcia C. , De Souza Aglecio , Bella Geruza P. , Grassi‐Kassisse Dora M. , Tacla Artur P. , Spadari‐Bratfisch Regina C.
Published: November 2009

We have analyzed the perceived stress index, the basal salivary cortisol levels, and the awakening cortisol response (ACR) in 86 volunteers of low (LSES) and high socioeconomic status (HSES). The LSES presented higher perceived stress index and basal salivary cortisol levels, nonaltered ACR, or cortisol diurnal rhythm. We have concluded that the LSES is associated with high perceived stress index and salivary cortisol levels, which could impact negatively in health, and that it is related to the daily life stress experienced by individuals in the LSES group. Because the LSES corresponds to about 30% of the total Brazilian population, this conclusion might have a great impact on public health policies and costs.
Adrenomedullary Response to Hypoglycemia in First‐degree Relatives of Patients with Rheumatoid Arthritis
Authors: Rovensky J. , Imrich R. , Penesova A. , Radikova Z. , Scipova A. , Vlcek M. , Vigas M.
Published: November 2009

Our recent studies showed blunted adrenomedullary responses to insulin‐induced hypoglycemia in premenopausal females with rheumatoid arthritis (RA) and systemic sclerosis, suggesting dysregulation of the adrenomedullary hormonal system (AMHS). Since no relationship has been found between degree of AMHS dysfunction and clinical or inflammatory parameters in those patients, we hypothesize the presence of an inherited perturbation of the AMHS. To test this hypothesis, we evaluated adrenomedullary responses to insulin‐induced hypoglycemia (0.1 IU/kg) in premenopausal female subjects: 17 glucocorticoid‐naïve RA patients, 15 healthy first‐degree family members (FDR), and 18 age‐ and body mass index–matched healthy controls. Our results demonstrate that when compared to controls, RA patients had lower baseline epinephrine levels (P= 0.01) and lower area under response curve (AUC) levels of norepinephrine (P < 0.001) and epinephrine (P < 0.003). In contrast, FDR had lower (P= 0.001) AUC levels of norepinephrine compared to controls and higher (P= 0.033) AUC levels of epinephrine compared to RA patients. There were no significant differences in epinephrine response between FDR and controls. Although we found lower norepinephrine responses to hypoglycemia in FDR of RA patients, adrenomedullary responses to hypoglycemia does not appear to be altered to the degree found in RA patients.
Peripheral Lipopolysaccharide Administration Affects the Olfactory Dopamine System in Mice
Authors: Ota Akira , Mori Keiji , Kaneko Yoko S. , Nakashima Akira , Nagatsu Ikuko , Nagatsu Toshiharu
Published: November 2009

Peripheral administration of lipopolysaccharide (LPS) in an amount that produces acute stress has been found to affect the catecholamine systems in the brain. Acute peripheral LPS administration activated norepinephrine (NE) metabolism in the locus ceruleus (LC). Approximately 40% of murine LC neurons project to the olfactory bulb (OB) and the anterior olfactory nucleus (AON). Thus, we investigated the effects of a single intra‐peritoneal (i.p.) LPS injection on catecholamine biosynthesis in the OB and AON in 8‐week‐old C3H/HeN male mice. In the AON, the content of dopamine (DA), but not that of NE, was highly increased 6 h after LPS injection. In the OB, the contents of DA and NE did not change; but within 2 h after a single i.p. LPS injection, the mRNA levels of IκB, TNF‐α, and TNF‐α receptor type 1 were significantly enhanced. Almost all TNF‐α‐immunoreactive cells in the OB of the LPS‐injected mice were located in the granule cell layer, and unexpectedly, they were not microglia but astroglia. The number of TUNEL‐positive cells identified exclusively in the granule cell layer was significantly increased at 24 h after LPS injection. Therefore, our data suggest that astroglia activated by peripherally injected LPS may release TNF‐α, which may trigger apoptosis in the granule cell layer in the OB. The increase in DA content in the AON and the production of TNF‐α and apoptotic cells in the OB by acute peripheral LPS administration are not likely to be related.
Differential Effects of the New Glucocorticoid Receptor Antagonist ORG 34517 and RU486 (Mifepristone) on Glucocorticoid Receptor Nuclear Translocation in the AtT20 Cell Line
Authors: Peeters B.W.M.M. , Ruigt G.S.F. , Craighead M. , Kitchener P.
Published: November 2009

Glucocorticoid agonists bind to cytoplasmic glucocorticoid receptors (GRs) and subsequently translocate as an agonist‐GR complex into the nucleus. In the nucleus the complex regulates the transcription of target genes. A number of GR antagonists (RU486, progesterone, RU40555) have also been shown to induce receptor translocation. These compounds should be regarded as partial agonists. For the nonselective progesterone receptor antagonists, RTI3021‐012 and RTI3021‐022, it was shown that GR antagonism is possible without the induction of GR translocation. In the present studies, the new GR antagonist, ORG 34517, was investigated for its potential to induce GR translocation and to antagonize corticosterone‐induced GR translocation in the AtT20 (mouse pituitary) cell line. ORG 34517 was compared to RU486. In contrast to RU486, ORG 34517 (at doses up to 3 × 10−7 M) did not induce GR translocation, but was able to block corticosterone (3 × 10−8 M) induced GR translocation. ORG 34517 can be regarded as a true competitive GR antagonist without partial agonistic activities.
Corticosterone Regulates pERK1/2 Map Kinase in a Chronic Depression Model
Authors: Gourley Shannon L. , Wu Florence J. , Taylor Jane R.
Published: November 2009

Neurotransmitter‐ or neurotrophin‐regulated intracellular signaling in the hippocampus is hypothesized to contribute to depression and antidepressant (ADT) efficacy. Extracellular signal‐regulated kinase 1/2 (ERK1/2) is downstream of several receptor types and regulates transcriptional activity of many targets; ERK1/2 may thereby influence mood and affect. Using a novel, ADT‐sensitive depression model in mice, we show that prior corticosterone exposure decreases motivated behavior, sucrose consumption, and pERK1/2 in the dentate gyrus, but not in CA1/CA3. Notably, prefrontal cortical targets were also regulated. Our data suggest ADTs restore hippocampal pERK1/2 after stress‐related insult, and potentially reveal a novel role for prefrontal neurotrophins in depressive‐like symptomology.
Fast Action of Neuroactive Steroids on Plasma Membrane Calcium Pump in PC12 Cells
Authors: Zylinska Ludmila , Kowalska Iwona , Kozaczuk Anna
Published: November 2009

Calcium ions are essential to proper neurotransmission. Impairment in cytosolic Ca2+ concentration and Ca2+ signaling disturbs neuronal activity, leading to pathological consequences. In cells, a high‐affinity plasma membrane calcium pump (PMCA) keeps free Ca2+ in the nanomolar range. Among four genes encoding the enzyme, PMCA2 and 3 are primary in excitable cells. To elucidate the relationship between PMCAs' composition and susceptibility for neurosteroid regulation, we obtained PC12 cells with suppressed neuron‐specific isoforms and analyzed the effect of selected steroids on Ca2+ uptake. Our results indicate that hormones affected Ca2+ transport activity and that this effect depended on both PMCA isoform composition and steroid structure.
Catecholamines and Estrogen Are Involved in the Pathogenesis of Emotional Stress‐induced Acute Heart Attack
Authors: Ueyama Takashi , Kasamatsu Ken , Hano Takuzo , Tsuruo Yoshihiro , Ishikura Fuminobu
Published: November 2009

Emotional stress triggers takotsubo cardiomyopathy in postmenopausal women. Clinical analysis of autonomic nervous function has revealed a transient increase of sympathetic nervous activity and decrease of vagal nervous activity. Immobilization (IMO) stress of rats can reproduce the electrocardiographic and left ventriculographic changes that occur in takotsubo cardiomyopathy, both of which are prevented by combined blockade of α‐ and β‐adrenoceptors. Estrogen supplementation partially attenuated these cardiac changes. It also attenuated the IMO‐induced increase of c‐Fos immunoreactivity, orc‐fosmRNA expression in the lateral septum, medial amygdaloid nucleus, paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, laterodorsal tegmental nucleus, and locus ceruleus; these regions contain central sympathetic neurons and neurons with immunoreactive estrogen receptors. It also downregulatedc‐fosmRNA expression in the adrenal gland and the heart, suggesting an increase of estrogen attenuated the stress‐induced hypothalamo‐sympathoadrenal outflow from the central nervous system to the target organs. Estrogen treatment also upregulated the levels of cardioprotective substances, such as atrial natriuretic peptide and heat shock protein 70, in the heart. These data suggest that reduction of estrogen levels following menopause might be involved in the primary cause of takotsubo cardiomyopathy both by indirect action on the nervous system and by direct action on the heart.
Central Neuropeptide Y in Anxiety‐ and Stress‐related Behavior and in Ethanol Intake
Authors: Thorsell Annika
Published: November 2009

One of the most profound properties of central neuropeptide Y (NPY) is its anxiolytic, or anti‐anxiety, effect. This has been demonstrated repeatedly in a number of animal models. In addition, stressors affect NPY expression in the central nervous system, with acute and repeated (chronic) stress having differential effects. Here, a brief summary of some work performed in our laboratory is presented that supports a role for NPY in regulation of stress responses and behaviors.
Adrenergic Polymorphism and the Human Stress Response
Authors: Rao Fangwen , Zhang Lian , Wessel Jennifer , Zhang Kuixing , Wen Gen , Kennedy Brian P. , Rana Brinda K. , Das Madhusudan , Rodriguez‐Flores Juan L. , Smith Douglas W. , Cadman Peter E. , Salem Rany M. , Mahata Sushil K. , Schork Nicholas J. , Taupenot Laurent , Ziegler Michael G. , O'Connor Daniel T.
Published: November 2009

Tyrosine hydroxylase (TH) is the rate‐limiting enzyme in catecholamine biosynthesis. Does common genetic variation at human TH alter autonomic activity and predispose to cardiovascular disease? We undertook systematic polymorphism discovery at the TH locus, and then tested variants for contributions to sympathetic function and blood pressure. We resequenced 80 ethnically diverse individuals across the TH locus. One hundred seventy‐two twin pairs were evaluated for sympathetic traits, including catecholamine production and environmental (cold) stress responses. To evaluate hypertension, we genotyped subjects selected from the most extreme diastolic blood pressure percentiles in the population. Human TH promoter haplotype/reporter plasmids were transfected into chromaffin cells. Forty‐nine single nucleotide polymorphisms (SNPs) and one tetranucleotide repeat were discovered, but coding region polymorphism did not account for common phenotypic variation. A block of linkage disequilibrium spanned four common variants in the proximal promoter. Catecholamine secretory traits were significantly heritable, as were stress‐induced blood pressure changes. In the TH promoter, significant associations were found for urinary catecholamine excretion, as well as blood pressure response to stress. TH promoter haplotype #2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and blood pressure during stress. In hypertension, a case–control study (1266 subjects, 53% women) established the effect of C‐824T in determination of blood pressure. We conclude that human catecholamine secretory traits are heritable, displaying joint genetic determination (pleiotropy) with autonomic activity and finally with blood pressure in the population. Catecholamine secretion is influenced by genetic variation in the adrenergic pathway encoding catecholamine synthesis, especially at the classically rate‐limiting step, TH. The results suggest novel pathophysiological links between a key adrenergic locus, catecholamine metabolism, and blood pressure, and suggest new strategies to approach the mechanism, diagnosis, and treatment of systemic hypertension.
Effects of a Mixed Meal on Hemodynamics and Autonomic Control of the Heart in Patients with Type 1 Diabetes
Authors: Cozzolino Domenico , Furlan Raffaello , Gruosso Domenico , Di Maggio Cristiana , Miraglia del Giudice Emanuele , Torella Roberto , Giugliano Dario
Published: November 2009

Context: Food intake induces relevant cardiovascular changes together with parallel increases in cardiac sympathetic activity and insulin plasma levels in man.

Objective: We evaluated hemodynamics, neurohormones, and cardiac autonomic control after eating in patients with type 1 diabetes, a disease characterized by the absence of basal and stimulated insulin production.

Design and Setting: Fifteen type 1 diabetic patients and 15 healthy controls underwent blood sampling, electrocardiogram, blood pressure and respiration recordings, and heart rate variability analysis while recumbent, during the 70° head-up tilt, and 20 min after a mixed meal; on another occasion, diabetic patients were also studied 20 min after a mixed meal preceded by their scheduled bolus of exogenous insulin. Spectrum analysis of RR interval provided the indices of sympathetic (LFRR) and vagal (HFRR) modulation of the sinoatrial node.

Results: At baseline, no significant differences were found between groups, except for metabolic parameters. Compared with baseline, heart rate, plasma catecholamines, and LFRR significantly (P < 0.005) increased, whereas HFRR significantly (P < 0.0001) decreased during the tilt in all subjects. Compared with baseline, plasma norepinephrine, heart rate, and LFRR significantly (P < 0.05) increased, whereas HFRR significantly (P < 0.02) decreased after eating in controls but not in diabetic patients (with and without insulin administered before eating). In both controls and diabetic patients, no relationship between postprandial changes of insulin and LFRR and HFRR was found.

Conclusions: Hemodynamic, neurohormonal, and cardiac neural responses to eating are abnormal in type 1 diabetic patients, independently of insulin.
AT&T's Antigovernment Lesson-Drawing in the Political Economy of Networks, 1905–20
Authors: Kielbowicz Richard B.
Published: November 2009

Many Progressive Era reformers, lawmakers, and economists believed that free market competition failed to maximize the public benefits of telecommunication networks. When proposals to place the nation's telecommunication system under the post office gained currency, AT&T responded with its Brief of Arguments against Public Ownership (1913–17). Resembling a loose-leaf service for lawyers, the Brief furnished opinion leaders with more than three hundred items of evidence, some drawn from economists, about the failings of government-run enterprises. To impart lessons about the consequences of nationalizing telecommunication, AT&T assembled evidence from three domains, most notably foreign nations' experience with government ventures. Analyzing the Brief reveals how AT&T structured and popularized arguments that justified the anomalous place of telecommunication networks in American political economy.
A Marshall-Walras Divide? A Critical Review of the Prevailing Viewpoints
Authors: De Vroey Michel
Published: November 2009

The aim of this essay is to examine economists' views about the relationship between Marshallian and Walrasian theory. Are they complementary, as is usually believed, or do they constitute alternative research programs? I compare two viewpoints on this matter, the conciliatory and the antagonistic. After describing these, I present my own standpoint: I believe that there is a Marshall–Walras divide, but I have serious objections to the way in which the argument for this divide is usually made. In the last part of the paper, I examine the view held by several authors that an embryonic general equilibrium model is to be found in Marshall's Principles.
Alfred Russel Wallace and the Political Economists
Authors: Collard David
Published: November 2009

Alfred Russel Wallace is famous as the co-discoverer with Darwin of the mechanism of natural selection. He was also an enthusiastic economic and social reformer. This article considers the relationship of Wallace's work to that of a number of eminent economists, including Malthus, Mill, Marshall, and Fisher. Wallace's economics, which attempted to analyze practical socialism, protection of the environment, and monetary stability, was interesting and insightful. It was only loosely related to his evolutionary theory.
Violence and Civility: On the Limits of Political Anthropology
Authors: Balibar Étienne
Published: November 2009

The essay offers a series of reflections on the place of violence in politics and, at the same time, on the ways in which the relation between what might be understood as mutually exclusive categories (violence ceases where politics begins and vice versa) has been theorized, especially in the twentieth century. The condition of such an inquiry is not a set of abstract concepts, but a phenomenology of extreme violence that exceeds any rational political objective. Such violence is often theorized through such negative categories as evil or extermination and thus continues in some measure to resist efforts to comprehend it. To begin to acknowledge the historical and material forms of the existence of violence is to confront the “tragic” dimension of the practice of politics. Just as this practice can never abandon itself to violence, so it can never altogether abandon violence, especially in the forms of resistance and insurrection.