Biomedical subjects

D Jezova

Publications and source records attributed to D Jezova.

At least 37 records · Page 2Linked to original sources

PubMed2002

Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761) in healthy volunteers.

The standardized extract of Ginkgo biloba (EGb 761) was found not only to improve memory and aging associated cognitive deficits but also to exert beneficial effects on mood. An antistress action of the extract has been suggested but not directly proven. The present study was aimed to evaluate the effects of EGb 761 on salivary cortisol and blood pressure responses during stress in healthy young volunteers (n = 70) in a double blind placebo controlled design. A stress model involving a combination of static exercise (handgrip) and mental stimuli was used. Single treatment with EGb 761 (120 mg) reduced stress-induced rise in blood pressure without affecting the heart rate. Salivary cortisol responses showed differences with respect to the gender and the time of day of the stress exposure, with the activation only in male subjects in the afternoon. This activation was absent if they were treated with EGb 761. The performance in a short memory test with higher scores achieved by women remained unaffected by EGb 761 treatment. Thus, this study provides evidence that EGb 761 has an inhibitory action on blood pressure and it may influence cortisol release in response to some stress stimuli.

Adult↗

PubMed2002

'Neutral point titration': cardiovascular regulation during combined (LBNP/HDT vs. LBPP/HUT) stimulation.

This study was undertaken to identify combinations ('neutral points', NP) of orthostatic (tilt: head-down = HDT, head-up = HUT) and pseudo-orthostatic (lower body pressure: positive = LBPP, negative = LBNP) stimuli able to compensate one another in their effect on hemodynamic variables, electrical thoracic impedance (TI), hematocrit and plasma mass density (PD), and blood hormone concentrations. We asked if NP's exist for tested variables (hypothesis 1), if NP's differ with variables (hypothesis 2), and if NP's change as a function of time (hypothesis 3). For the blood volume sensitive variables (PD, plasma total protein concentration, and hematocrit) we found a NP at > or = 30 degrees HDT at LBNP-35 and -15 degrees HUT with LBPP+35. There was no clear PD / total plasma protein concentration effect with various degrees of LBNP-15 / HDT. NP's could be derived for some hemodynamic variables: With LBNP-35, a NP for heart rate was derived at -25 degrees HDT and for MAP at -30 degrees HDT. Heart rate intersected at > or = 30 degrees HDT with LBNP-15 (extrapolated), stroke volume index (SVI) at -20 degrees HDT. With LBPP+35, SVI had its NP at 11 degrees HUT. The hormonal responses displayed a pattern where plasma renin activity (PRA) NP's were logically scattered with LBNP intensity, whereas aldosterone displayed similar NP's with both LBNP intensities.

Comparative Study↗

PubMed2001

Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats.

The effects of chronic immune challenge on cytokine expression and hypothalamic-pituitary-adrenal axis (HPA) axis responses to stress were studied in Wistar rats after administration of increasing doses of lipopolysaccharide (LPS). Repeated LPS (R-LPS) decreased body weight and increased adrenal weight and pituitary pro-opiomelanocortin mRNA levels. LPS injection increased plasma adrenocorticotropic hormone (ACTH) and corticosterone but the effect was attenuated in R-LPS. Plasma corticosterone but not ACTH responses to restraint were also reduced in R-LPS. Basal and restraint-stimulated corticotropin releasing hormone (CRH) mRNA levels were lower in R-LPS, but responses to a new LPS injection were similar to controls. In contrast, type 1 CRH receptor (CRH-R1) mRNA responses to both LPS and restraint were blunted in R-LPS. Vasopressin mRNA levels in parvocellular neurones were higher in R-LPS, and increased further after restraint but not after a new LPS injection. Glucocorticoid receptor (GR) levels in the paraventricular nucleus (PVN) increased after a single LPS or R-LPS (24 h after the last injection) but declined after a new injection in R-LPS. Interleukin (IL)-1beta and IL-6 mRNAs increased in the pituitary, spleen and circumventricular organs after single or R-LPS, suggesting that cytokines may contribute to the activation of the HPA axis though pathways from the circumventricular organs as well as paracrine effects in the pituitary. The data show that (i) adaptation of the HPA axis during repeated LPS injection involves increases in vasopressin : CRH expression ratios in parvocellular neurones; (ii) that hypothalamic CRH and vasopressin responses to acute stimulation are independent of CRH-R1 expression in the PVN; and (iii) there is a dissociation between pituitary and adrenal responses to acute stress suggesting a decrease of adrenal sensitivity to ACTH.

Adrenocorticotropic Hormone↗

PubMed2001

Differential responses to stress stimuli of Lewis and Fischer rats at the pituitary and adrenocortical level.

OBJECTIVE: Histocompatible rat strains Lewis (LEW) and Fischer 344 (F344) are often used to study hypothalamic-pituitary-adrenocortical axis function in relation to immune system activity. It has been suggested that LEW rats have a defect in the hypothalamic production of corticotropin-releasing hormone. The aim of this study was to clarify differential responsiveness of LEW and F344 rat strains to acute stress by measuring adrenocorticotropic hormone (ACTH) and corticosterone concentrations in plasma, corticosterone in adrenal cortex and proopiomelanocortin (POMC) gene expression in the pituitary and spleen. METHODS: Two separate experiments were performed. In the first, indwelling catethers were used for blood sampling from conscious animals during immobilization stress. In the second experiment, rats were immobilized for two hours and decapitated after another 3 hrs for organ collection. RESULTS: Our results show that LEW strain hyporeactivity was evident from significantly lower ACTH and corticosterone levels compared to those in F344 at all time intervals during stress studied. Measurement of POMC gene expression in the pituitary revealed that the difference in hormone secretion was consistent with POMC mRNA concentrations in these strains of rats. On the other hand, corticosterone concentrations in the adrenal cortex after stress were significantly higher in LEW rats compared to F344. No differences in spleen POMC mRNA concentrations between LEW and F344 rats were found. CONCLUSION: The results show that differential reactivity of LEW and F344 rats is associated with different POMC gene expression in the pituitary and probably other factors on the adrenocortical level.

Adrenal Cortex↗

PubMed2001

Changes in angiotensin AT1 receptor mRNA levels in the rat brain after immobilization stress and inhibition of central nitric oxide synthase.

OBJECTIVE: To study functional interactions between angiotensin II AT1 receptors and nitric oxide (NO) activity in different brain areas in rats exposed to immobilization stress. METHODS: Central inhibition of nitric oxide synthase (NOS) was provided by intracerebroventricular (i.c.v.) administration of (N-omega-nitro-L-arginine-methylester) L-NAME and analysis of AT1 receptor mRNA was performed using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. The immobilization in prone position lasted 2 hrs and the rats were sacrificed 24 hr later. The hypothalamus, hippocampus, thalamus, and cortex were isolated from fresh brains. RESULTS: In the cortex, gene expression of AT1 receptors was unaffected either by L-NAME treatment, or by a single exposure to immobilization stress for 2 hours followed by 24 hours of rest. In the hippocampus, the repeated treatment with L-NAME increased mRNA levels of AT1 receptors approximately 9-times compared to those in the control (untreated) group. Immobilization also increased AT1 receptor mRNA levels in the hippocampus which was similar to that induced by the L-NAME. The increase of AT1 receptor mRNA levels in the hippocampus of immobilized rats was not further altered when the animals were pretreated with L-NAME. In control rats, exposure to immobilization resulted in a significant rise in mRNA levels coding for AT1 receptors in the hypothalamus, but not in the thalamus. L-NAME treatment showed a tendency of increase in AT1 receptor mRNA levels in the hypothalamus. Moreover, when animals treated with L-NAME were subjected to immobilization, a further increase in AT1 receptor mRNA levels was observed in the hypothalamus in comparison with corresponding controls. CONCLUSIONS: The present data indicate that a single immobilization stress results in increased gene expression of AT1 receptors in the hypothalamus and hippocampus. The rise in AT1 mRNA levels in the same brain structures after repeated treatment with L-NAME allow to suggest an interaction between the central angiotensin II and nitric oxide.

Animals↗

PubMed2001

Single dose of morphine influences plasma corticosterone and gene expression of main NMDA receptor subunit in the adrenal gland but not in the hippocampus.

OBJECTIVE: This study was aimed to evaluate the effects of morphine on hypothalamo-pituitary-adrenocortical (HPA) axis, namely proopiomelanocortin (POMC) mRNA and plasma corticosterone, in relation to its influence on glutamate receptor gene expression in central and peripheral sites related to HPA axis regulation. As previous data on morphine action were obtained mainly in male rats, these experiments were performed in females to see potential gender differences. METHODS: Adult female Sprague-Dawley rats were injected with a single dose of morphine (10 mg/kg s.c.) or vehicle. Blood and tissues were sampled 4 h and 24 h following the treatment. In situ hybridization was used to measure POMC mRNA concentrations, reverse transcription-polymerase chain reaction to quantify mRNA coding for N-methyl-D-aspartic acid (NMDA) receptor subunit 1 and radioimmunoassay to measure plasma corticosterone. RESULTS: Single dose of morphine was followed by a decrease in gene expression of glutamate receptor subunit NMDAR1 in the adrenal gland. Concentrations of mRNAs coding for NMDAR1 in the hippocampus and for POMC in the anterior pituitary remained unaffected. However, plasma corticosterone levels, which were measured at 4 and 24 h after the treatment with morphine, showed a disturbed daily variation in corticosterone release. The efficacy of morphine was confirmed by Straub tail response, one of the classical effects of this drug, in mice. CONCLUSIONS: Present data obtained in females allow to suggest that morphine exerts some of its effects on HPA axis by POMC unrelated mechanisms seemingly in a gender specific manner. Decrease in glutamate receptor gene expression in adrenals induced by a single dose of morphine may result in a modulation of adrenal function in response to subsequent exposure to opioids and contribute to some alterations occurring during opioid drug abuse.

Adrenal Glands↗

PubMed2001

Lesion of central part of the dorsomedial nucleus alters vasopressin but not corticotropin releasing hormone mRNA levels in rat hypothalamic paraventricular nucleus.

Functional significance of neural projections from the hypothalamic dorsomedial nucleus (DMN) to the paraventricular nucleus (PVN) was investigated using surgical lesion of the central part of the DMN. Under basal conditions, DMN lesion resulted in a decrease in magnocellular vasopressin (AVP) mRNA levels in the PVN, rise in pituitary proopiomelancortin (POMC) mRNA concentrations and elevated plasma corticosterone levels. Corticotropin-releasing hormone (CRH) mRNA levels remained unaffected. In sham operated animals, osmotic stress induced by hypertonic saline injection failed to modify AVP mRNA, but increased CRH and POMC mRNA levels and peripheral hormone release. The rise in CRH mRNA levels after osmotic stress was potentiated in DMN lesioned animals. Thus, the DMN participates in the control of hypothalamic peptide gene expression and pituitary adrenocorticotropic function.

Animals↗

PubMed1999

Central corticotropin-releasing hormone receptors modulate hypothalamic-pituitary-adrenocortical and sympathoadrenal activity during stress.

The role of brain corticotropin-releasing hormone receptors in modulating hypothalamic-pituitary-adrenal and sympathoadrenal responses to acute immobilization stress was studied in conscious rats under central corticotropin-releasing hormone receptor blockade by intracerebroventricular injection of a peptide corticotropin-releasing hormone receptor antagonist. Blood for catecholamines, adrenocorticotropic hormone and corticosterone levels was collected through vascular catheters, and brains were removed at 3 h for in situ hybridization for tyrosine hydroxylase messenger RNA in the locus coeruleus, and corticotropin-releasing hormone and corticotropin-releasing hormone receptor messenger RNA in the hypothalamic paraventricular nucleus. Central corticotropin-releasing hormone receptor blockade reduced the early increases in plasma epinephrine and dopamine, but not norepinephrine, during stress. Immobilization stress increased tyrosine hydroxylase messenger RNA levels in the locus coeruleus by 36% in controls, but not in corticotropin-releasing hormone antagonist-injected rats. In control rats, corticotropin-releasing hormone messenger RNA and type 1 corticotropin-releasing hormone receptor messenger RNA in the paraventricular nucleus increased after stress (P<0.01), and these responses were attenuated by central corticotropin-releasing hormone receptor blockade. In contrast, central corticotropin-releasing hormone antagonist potentiated plasma adrenocorticotropic hormone responses, but slightly attenuated plasma corticosterone responses to stress. The inhibition of plasma catecholamine and locus coeruleus tyrosine hydroxylase messenger RNA responses to stress by central corticotropin-releasing hormone receptor blockade supports the notion that central corticotropin-releasing hormone regulates sympathoadrenal responses during stress. The attenuation of stress-induced corticotropin-releasing hormone and corticotropin-releasing hormone receptor messenger RNA responses by central corticotropin-releasing hormone receptor blockade suggests direct or indirect positive feedback effects of corticotropin-releasing hormone receptor ligands on corticotropin-releasing hormone expression, whereas additional mechanisms potentiate adrenocorticotropic hormone responses at the pituitary level. In addition, changes in neural activity by central corticotropin-releasing hormone are likely to modulate adrenocortical responsiveness during stress.

Adrenal Cortex↗

PubMed1999

Single stress induces long-lasting elevations in vasopressin mRNA levels in CRF hypophysiotrophic neurones, but repeated stress is required to modify AVP immunoreactivity.

Repeated stress is known to induce an increased vasopressin (AVP) expression in paraventricular corticotrophin-releasing factor (CRF) neurones which is supposed to enhance the ACTH-releasing capacity of these cells. To test the hypothesis that a single stress is sufficient to produce these changes, we used quantitative in-situ hybridization analysis to measure steady state CRF and AVP mRNA. Moreover the colocalized AVP and CRF immunoreactive sites were assessed in the dense core vesicle compartment of CRF axon terminals in the external zone of the median eminence with quantitative immunoelectron microscopy. Acute immobilization produced a significant increase in the average AVP and CRF mRNA levels (145% and 65%, respectively, above control values) in the medial parvocellular subdivisions of the paraventricular nucleus (PVN), and these changes persisted for over 4 days after stress. In contrast to these changes in AVP mRNA levels, there were no concomitant changes in AVP immunostaining in CRF terminals and axons during the 4-day period. However, when immobilization stress was repeated daily, the number of CRF terminals containing AVP increased progressively. Moreover, the ratio of AVP and CRF immunoreactivity in the dense core vesicle compartment was increased. Taken together, these results provide evidence that single stress experience can cause long-lasting changes in AVP and CRF mRNA steady state expression that is not apparently accompanied by changes in peptide levels. They also suggest that repeated stress is required for developing progressive shifts in the neurohormone storage pattern of these neurones.

Animals↗

PubMed1999

Simultaneous blockade of two glutamate receptor subtypes (NMDA and AMPA) results in stressor-specific inhibition of prolactin and corticotropin release.

Many neurons express simultaneously two or more isotypes of glutamate receptors, so that pharmacological modulation of more than one receptor may be necessary to reveal the role of glutamate in mediating physiological processes. The present studies were aimed at evaluating involvement of endogenous glutamate in triggering plasma prolactin (PRL) and adrenocorticotropic hormone (ACTH) levels in response to three different stress stimuli (footshock, immobilization and ether stress). Blockade of glutamate receptor subtypes was achieved by the administration of the NMDA antagonist dizocilpine (MK-801, 0.2 mg/kg) and the selective AMPA antagonist GYKI 52466 (10 mg/kg). Rats were pretreated for 4-5 days and then exposed to stressful stimulation. Basal hormone levels were not affected by the antagonists. In male rats, combined, but not separate blockade of NMDA and AMPA/kainate subtypes of glutamate receptors prevented the rise in plasma PRL in response to footshock stress. In female rats, footshock-induced PRL release was inhibited even by separate blockade of NMDA receptors by dizocilpine, suggesting that the PRL system of females is more sensitive to the effect of NMDA antagonists than that of males. None of the treatments affected PRL release during immobilization or ether stress. Simultaneous blockade of NMDA and AMPA receptor subtypes resulted in a mild inhibition of immobilization-induced ACTH release without any effect on ACTH response to footshock or ether stress. The data suggest that involvement of glutamatergic pathways in neuroendocrine response during stress is selective for discrete stress stimuli and stress hormones. In addition a concerted action of glutamate on both NMDA and non-NMDA receptor subtypes is involved in the control of PRL release during footshock stress.

Adrenocorticotropic Hormone↗

PubMed1999

Postnatal monosodium glutamate treatment results in attenuation of corticosterone metabolic rate in adult rats.

OBJECTIVE: To study the basal and ACTH stimulated production of corticosterone by adrenal cortex on one hand and the binding and degradation of corticosterone in the liver of adult rats which were treated with monosodium glutamate (MSG) during the neonatal period. METHODS: Male offsprings of Sprague-Dawley rats were injected i.p. with MSG (4 mg/g of b.w. in saline) on alternated days for the first 10 days of life, their littermates being used as controls. On the 21st postnatal day they were weaned and used for the observation at the age of 65-75 days. After sacrifice the level of corticosterone in serum and the release of corticosterone from incubated adrenals under basal and ACTH stimulated conditions (ACTH in 6 concentrations from 1.25 to 80 mU/ml medium) were estimated. In addition, glucocorticoid binding to cytosol receptors in the liver and muscle tissues was determined. Corticosterone degradation rate was measured by decrease of corticosterone concentration added to the medium after the incubation with liver slices. RESULTS: Adult rats neonatally treated with MSG had reduced weight of adrenal glands, while plasma corticosterone levels and its basal production by adrenals in vitro were significantly higher than in controls. In MSG treated rats the stimulation of corticosterone production by ACTH was diminished. Glucocorticoid binding to liver cytosolic receptors was significantly decreased, while that in muscle tissue was only slightly elevated. Moreover, a decreased corticosterone degradation rate in liver slices was observed in rats treated neonatally with MSG. CONCLUSIONS: These results are in agreement with previously observed decrease of corticosterone clearance rate in MSG treated animals and suggest that elevated corticosterone levels in plasma and its prolonged response to stressogenic stimulation are due to elevated corticosterone production in adrenals and lower degradation rate in the liver.

Adrenal Cortex↗

PubMed1999

Changes in plasma catecholamine and corticosterone levels and gene expression of key enzymes of catecholamine biosynthesis in partially hepatectomized rats.

OBJECTIVE: To reexamine the possible role of catecholamines and corticosterone in the early period of liver regeneration after partial hepatectomy (PH)in conscious cannulated rats under carefully controlled conditions which would allow to obtain reliable information about sympathetic-adrenomedullary function after PH in the rat in vivo. METHODS: Plasma levels catecholamines (epinephrine - EPI, norepinephrine - NE) were estimated by radioenzymatic assay and these of corticosterone by competitive protein binding assay. The total RNA was isolated from the adrenals and tyrosine hydroxylase (TH) mRNA expression was estimated by hybridisation with cDNA after Northern blot. The level of immunoreactive protein was measured by using a monoclonal antibody to rat TH, visualized by Western light chemiluminescent detection system and analyzed by densitometry. The level of TH in adrenals was estimated with the aid of 3H-tyrosine and TH cofactor DL-6-methyl-5,6,7,8-tetrahydropterine and the formed radioactive water was measured by scintillation spectometry. RESULTS: The plasma level of norepinephrine (NE), epinephrine (EPI) and corticosterone rapidly increased 20 min. after PH or sham operation (laparotomy). Although the increase of plasma NE was about the same after both PH and laparotomy, that of EPI and corticosterone in PH rats was significantly higher as compared to the laparotomy. One hour after the surgery plasma NE levels in both groups decreased to the basal value and remained still unchanged 4 and 24 h later. At the interval of 4h the plasma level of EPI was higher than in laparotomized controls, but after 24 h the EPI levels returned to basal values. Adrenal tyrosine hydroxylase (TH) mRNA level was significantly elevated in both PH and laparotomized rats, however 24 h after the surgery they returned to the baseline. Adrenal TH immunoprotein levels and TH activity were significantly elevated in both groups 4 h after the surgery, while 24 h later they returned to the baseline in laparotomized rats bur remained elevated in PH rats. Adrenal phenylethanolamine N-methyl-transferase (PNMT) mRNA levels were increased 4 h after both the PH and laparotomy and declined within 24 h. CONCLUSIONS: The first peak of catecholamine and corticosterone levels might result from unspecific stressor associated with the surgery. These levels could be accompanied with the mechanism of the rat liver regeneration. Prolonged elevations of EPI found after PH seems to be specific for liver regeneration indicating that the rise in the adrenal TH mRNA appears to be translated into immunoreactive protein which further leads to the elevation of TH activity. These results contrast markedly with previous studies indicating that the regeneration is modulated predominantly by norepinephrine.

Anesthesia↗

PubMed1998

Monosodium glutamate lesions inhibit the N-methyl-D-aspartate-induced growth hormone but not prolactin release in rats.

Large doses of glutamate administered to newborn rats damage permanently the neurones in the hypothalamic arcuate nucleus containing the growth hormone releasing hormone and the prolactin inhibiting dopamine neuron cell bodies. Since adult animals that underwent neonatal glutamate treatment still have a relatively well functioning growth hormone and prolactin system, we tested whether in the adults the excitatory amino acid sensibility is changed. After i.v. injection of different doses (10 or 30 mg/kg) of N-methyl-D-aspartate (excitatory amino acid receptor subtype agonist) growth hormone levels were significantly increased in the control groups but there was no rise in neonatally glutamate treated male and female rats. The level of prolactin was increased by N-methyl-D-aspartate, too, but the glutamate treatment had no effect on the rise. Our study suggests that systemic administration of N-methyl-D-aspartate increases plasma growth hormone level by activating the growth hormone releasing cells in the arcuate nucleus, but the intact tuberoinfundibular dopaminergic pathway is not essential for its prolactin stimulatory effect.

Animals↗

PubMed1998

Brain angiotensin II modulates sympathoadrenal and hypothalamic pituitary adrenocortical activation during stress.

Angiotensin II (Ang II) type-1 (AT1) receptors are present in areas of the brain controlling autonomic nervous activity and the hypothalamic-pituitary-adrenal (HPA) axis, including CRH cells in the hypothalamic paraventricular nucleus (PVN). To determine whether brain AT1 receptors are involved in the activation of the HPA axis and sympathetic system during stress, we studied the effects of acute immobilization stress on plasma catecholamines, ACTH and corticosterone, and mRNA levels of CRH and CRH receptors (CRH-R) in the PVN in rats under central AT1 receptor blockade by the selective antagonist, Losartan. While basal levels of epinephrine, norepinephrine and dopamine in plasma were unaffected 30 min after i.c.v. injection of Losartan (10 microg), the increases after 5 and 20 min stress were blunted in Losartan treated rats (P < 0.05 for norepinephrine, and P < 0.01 for epinephrine and dopamine, vs controls). Basal or stress-stimulated plasma ACTH and corticosterone levels were unaffected by i.c.v. Losartan treatment. Using in situ hybridization studies, basal levels of CRH mRNA and CRH-R mRNA in the PVN were unchanged after i.c.v. Losartan. While Losartan had no effect on the increases in CRH-R mRNA levels 2 or 3 h after 1 h immobilization, it prevented the increases in CRH mRNA. The blunted plasma catecholamine responses after central AT1 receptor blockade indicate that endogenous Ang II in the brain is required for sympathoadrenal activation during immobilization stress. While Ang II appears not to be involved in the acute secretory response of the HPA axis, it may play a role in regulating CRH expression in the PVN.

Adrenal Cortex↗

PubMed1998

Early Postnatal Glutamate Treatment Results in Altered Vascular Responsiveness to Serotonin and Noradrenaline in Adult Rats.

OBJECTIVES: To evaluate possible alterations of vascular responsiveness to vasoactive hormones in the vessel preparations from adult rats treated neonatally with high doses of glutamate. METHODS: The responses to noradrenaline and serotonin in perfused hindlimb vascular bed and isolated renal artery were measured in MSG-treated (2 and 4 mg/g BW) and control groups of adult rats at the age of 10 weeks. Acetylcholine test was used to assess the endothelium-dependent relaxation of the hindlimb vascular preparation. The vessel specimens from this vascular bed were evaluated histologically. RESULTS: Vasoconstrictory responses to noradrenaline and serotonin were significantly reduced in the hindlimb vascular bed in MSG-treated rats. In the renal artery, a significant decrease of the responses to noradrenaline was found without significant changes in the responses to serotonin. The observed changes were more pronounced in groups treated with a high dose of MSG. Comparison of relaxing responses to acetylcholine in the hindlimb preparation did not show any statistically significant differences in control and MSG treated groups. Histological evaluation of this preparations did not reveal any endothelial damage or morphological changes of vessel wall. CONCLUSIONS: The obtained results showed reduced vascular responsiveness to vasoconstrictory agents in adult rats neonatally treated with MSG suggesting that early postnatal administration of glutamate may result in irreversible changes in cardiovascular function.

Journal Article↗

PubMed1997

Changes of exploratory behaviour and its habituation in rats neonatally treated with monosodium glutamate.

In an attempt to elucidate mechanisms involved in adaptation to a novel environment, consequences of neurotoxic damage induced by administration of monosodium glutamate (MSG) to both male (n = 42) and female (n = 45) rats in the early postnatal period were studied. Rats treated with MSG and appropriate controls were tested on postnatal days 21 and 65 for alterations of exploration and the rapidity of habituation changes in an open field test. Compared with intact animals, a high dose of MSG (4 mg/g) increased exploratory behaviour, with a subsequent decrease in the rapidity of habituation of male rats. Neonatal stress represented by hypertonic saline injection in a vehicle-control group induced a slight increase of exploratory behaviour as compared with intact animals. Males proved to be more vulnerable to neonatal MSG treatment and handling than females. These results suggest a negative effect of neonatal stress and treatment with MSG on habituation to a new environment in male rats.

Animals↗

PubMed1995

Vasopressin and oxytocin in stress.

Though oxytocin and vasopressin are similar in structure and are produced in the same brain regions, they show specific responses under stress conditions. In humans, increases in peripheral blood vasopressin appear to be a consistent finding during many acute stress situations, while in rats, vasopressin secretion is unresponsive to several stimuli known to induce ACTH and catecholamine release. Even decreases in vasopressin levels during stress were described. In accordance with others, we observed enhanced vasopressin release in response to stress stimuli with an osmotic component such as hypertonic saline injection but also during exposure of rats to a warm environment. Immobilization stress which fails to induce vasopressin release was reported to increase hypothalamic vasopressin mRNA and plasma vasopressin levels in chronically adreno-demedullated rats. Unlike vasopressin, oxytocin may be considered a typical stress hormone responding to osmotic as well as other stress stimuli. We found that acute exposure of rats to immobilization stress resulted in an increase in oxytocin mRNA level. In addition, we have shown that magnocellular neurons of the paraventricular nucleus, but not the supraoptic nucleus, are essential for oxytocin release during immobilization stress. The release of posterior pituitary hormones represents an important component of the stress response.

Animals↗

PubMed1995

Stress-induced changes in messenger RNA levels of N-methyl-D-aspartate and AMPA receptor subunits in selected regions of the rat hippocampus and hypothalamus.

The postsynaptic AMPA/kainate and N-methyl-D-aspartate-selective glutamate receptors are formed by several different subunits and the overall subunit composition of the receptor appears to determine its physiological and pharmacological properties. Although glutamatergic mechanisms have been implicated in various forms of hippocampal stress responses, the impact of stress on glutamate receptor subunit composition has not yet been elucidated. We have used cell-by-cell quantitative in situ hybridization to assess stress-induced changes in transcript levels of N-methyl-D-aspartate and AMPA receptor subunit genes in subdivisions of the rat hippocampus and hypothalamus that are implicated in the stress response. We found that 24 h after a single immobilization stress there was a significant increase in the cellular level of NR1 subunit messenger RNA (about 35-45% above control values) in hippocampal CA3 and CA1 pyramidal cells as well as in neurons of the hypothalamic supraoptic and paraventricular nuclei. Moreover, in the CA3 area we have detected a concomitant increase (50% above controls) in the level of NR2B subunit messenger RNA, while the expression of NR2A subunit gene did not change after stress. Stress induced a selective decrease in the level of AMPA receptor subunit glutamate receptor A messenger RNA in neurons of both the CA3 and CA1 areas (18 and 24%, respectively, below control values). These results suggest that the regulation of specific subunit messenger RNAs of the N-methyl-D-aspartate and AMPA receptors may be involved in altered hippocampal and hypothalamic responsiveness to glutamate and thus could play a critical role in stress-induced changes in their function.

Animals↗