Adrenovascular alterations from neurogenic stress modified by denervation of the adrenal gland in rat

The application of a painful stimulus to restrained rats provokes conspicuous adrenovascular alterations (vasodilatation, edema, small hemorrhages). Hypophysectomy does not prevent the adrenovascular response to stress, or the abdominal vagotomy. On the contrary, splanchnicotomy practically abolishes such response. These results show that the vascular alterations, consequence of the action of a neurogenic stress, are not caused by a hypophysohormonal response but by a sympathetic one.     

Self-stimulation reaction in normotensive and hypertensive rats

The part of noradrenergic mechanisms in self-stimulation (SS) operant behaviour was studied in rats. In all experiments systolic blood pressure (BP) in the tail artery was measured by means of photocells. It was found, that small doses of noradrenaline facilitate the SS, while high doses depress or stop it. The depressive effect is accompanied by a marked increase of BP. Effective blockade of beta-adrenoceptive structures by inderal suppresses SS, and the inhibitory effect is accompanied by a small decrease of BP. Suppressing effect of alpha-adrenoblocking agent, phentolamine, is even more pronounced, but is accompanied by a marked decrease of BP. Beta-agonist isadrin causes a marked facilitation of SS without changes of BP. It is suggested that positive reward in the lateral hypothalamus is due to a direct stimulation of beta-adrenoceptive noradrenergic neuronal elements. Chronic neurogenic hypertension is developed by an overloading of the higher nervous activity. In chronic hypertensive rats there is a pronounced suppression of SS. A transient fail of BP caused by injection of catapresan (hemiton) results in a temporary recovery of normal SS behaviour. It may be concluded that reduction of lever-pressing rate during acute and chronic neurogenic hypertensions is related to baroreceptor mechanisms. The role of the autonomic nervous system in SS behaviour is discussed.     

Effect of chronic psychogenic stress exposure on enkephalin neuronal activity and expression in the rat hypothalamic paraventricular nucleus

This study tested the hypothesis that the activation pattern of enkephalinergic (ENKergic) neurons within the paraventricular nucleus of the hypothalamus (PVH) in response to psychogenic stress is identical whether in response to repeated exposure to the same stress (homotypic; immobilization) or to a novel stress (heterotypic; air jet puff). Rats were assigned to either acute or chronic immobilization stress paradigms (90 min/day for 1 or 10 days, respectively). The chronic group was then subjected to an additional 90-min session of either heterotypic or homotypic stress. A single 90-min stress session (immobilization or air jet) increased PVH-ENK heteronuclear (hn) RNA expression. In chronically stressed rats, exposure to an additional stress session (whether homotypic or heterotypic) continued to stimulate ENK hnRNA expression. Acute immobilization caused a marked increase in the numbers of Fos-immunoreactive and Fos-ENK double-labeled cells in the dorsal and ventral medial parvicellular, and lateral parvicellular subdivisions of the PVH. Chronic immobilization caused an attenuated Fos response ( approximately 66%) to subsequent immobilization. In contrast, chronic immobilization did not impair ENKergic neuron activation within the PVH following homotypic or heterotypic stress. These results indicate that within the PVH, chronic psychogenic stress markedly attenuates the Fos response, whereas ENKergic neurons resist habituation, principally within the ventral neuroendocrine portion of the nucleus. This suggests an increase in ENK effect during chronic stress exposure. Homotypic (immobilization) and heterotypic (air jet) psychogenic stressors produce similar responses, including Fos, ENK-Fos, and ENK hnRNA, within each subdivision of the PVH, suggesting similar processing for painless neurogenic stimuli.     

Effects of hypothalamus destruction on the level of plasma corticosterone after blast injury and its relation to interleukin-6 in rats

Hypothalamus-pituitary-adrenal (HPA) axis is involved in the modulation of the innate immune response. The purpose of this study was to evaluate the dynamic relationship between plasma corticosterone and interleukin-6 in the hypothalamus-destroyed rats after blast injury. A total of 105 Sprague-Dawley rats were divided randomly into normal control (normal), sham operated (sham), blast injury plus sham operated (blast injury) and blast injury plus hypothalamus destruction groups. Symmetric electrolytic bilateral destruction of the hypothalamus was performed for the deeply anesthetic rats under sterile conditions. Seven days after the destruction of the hypothalamus, the animals were succumbed to moderate blast injury using a BST-I bioimpact machine. Plasma corticosterone and IL-6 levels were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. After blast injury, the corticosterone level in the hypothalamus-destroyed rats was significantly lower than that in the rats without destruction of hypothalamus at 3h (P<0.01) or from 5 to 8h (P<0.05). Reduction of corticosterone may be intrinsically correlated with the severe tissue injury and increased mortality (4/15 vs. 0/15, P<0.05). Circulating IL-6 level was markedly elevated in response to blast injury and hypothalamus destruction further increased IL-6 secretion (P<0.05). We concluded that elevation of pro-inflammatory IL-6 secretion might compensate the impaired HPA axis function after the trauma occurred in the hypothalamus-destroyed rats. These results also suggested that release of hypothalamus hormones is necessary to maintain certain magnitude of innate immunity after trauma.     

Injection of muscimol in dorsomedial hypothalamus and stress-induced Fos expression in paraventricular nucleus

Prior microinjection of the GABA(A)-receptor agonist muscimol into the dorsomedial hypothalamus (DMH) in conscious rats attenuates the increases in heart rate, blood pressure, and circulating adrenocorticotrophic hormone seen in air stress. Here, we examined the effect of similar treatment on air stress- or hemorrhage-induced Fos expression in the paraventricular nucleus (PVN). Muscimol (80 pmol/100 nl per side) or saline (100 nl per side) was microinjected bilaterally into the DMH in conscious rats before either air stress, an emotional or neurogenic stressor, or graded hemorrhage, a physiological stressor. Each stressor evoked a characteristic pattern of Fos expression in the parvocellular and magnocellular PVN after saline. Injection of muscimol into the DMH suppressed Fos expression in the PVN associated with air stress but not with hemorrhage. Injection of muscimol at sites anterior to the DMH and closer to the PVN had no effect on Fos expression in the PVN after air stress. Thus activation of neurons in the DMH is necessary for excitation of neurons in the PVN during air stress but not during hemorrhage.     

Deconstructing export of malaria proteins

Obesity is characterized by chronic activation of inflammatory pathways in peripheral tissues. In this issue, Zhang et al. (2008) demonstrate that inflammation also occurs in the central nervous system where it disrupts activity of the hypothalamus leading to resistance to leptin that is mediated by activation of IKK and the endoplasmic reticulum stress response.     

Mechanism of strengthening of the contractile activity in the duodenum and in the jejunum in psychogenic stress in rabbits

In experiments on unanaesthetized rabbits myoelectric activity (contractile activity index) of proximal (postpyloric) and distal sites of duodenum, and proximal part of jejunum was studied under stress induced by fastening a rabbit to a table in supine position. In both sites of duodenum, the stress impact induced a short-time decrease of contractile activity which was followed by its increase that exceeded the initial level. In the proximal part ofjejunum, the increase of contractile activity took place only during the second part of stress response. The strengthening of the contractile activity of the proximal part of duodenum was preserved after muscarinic or nicotinic cholinoceptor blockage, and after beta-receptor blockage. It was concluded that the contractile response of the proximal part of duodenum did not result from the contribution of central or local neurogenic mechanism, including excitatory cholinergic one, but was humoral in origin. The strengthening of the contractile activity of the distal part of duodenum and proximal part ofjejunum was abolished by muscarinic cholinoceptor and beta-receptor blockage, and resulted from the action of circulating catecholamines on the excitatory beta-adrenoceptor, localized on the cholinergic neurones of the enteric nervous system.     

The effects of stress on central nervous system concentrations of the opioid peptide, dynorphin

Dynorphin is an opioid peptide distributed throughout the central nervous system. Using a highly specific and sensitive radioimmunoassay for dynorphin we have examined the effect of stress on ir-dynorphin levels in the cortex and hypothalamus of the rat. Stresses related to food ingestion, i.e. starvation (72 hr), mild tail-pinch and insulin (10 U/kg) induced hypoglycemia all produced alterations in ir-dynorphin levels in the cortex. In contrast, restraint stress and 10-minute swim stress produced no changes in ir-dynorphin levels in either the hypothalamus or the cortex. Two hour exposure at 4°C resulted in a fall in ir-dynorphin levels in the hypothalamus. Taken together with previously reported pharmacological effects of dynorphin-(1–13), these results suggest a possible physiological role for dynorphin in appetite and temperature regulation.     

Effect of prolonged progesterone treatment on the proenkephalin mRNA gene expression and enkephalins concentration in the sheep brain

The opioids modulate reproduction in sheep mostly by inhibiting the activity of the hypothalamo-pituitary-gonadal axis. However, the mechanism by which the negative feedback control systems regulate opioid synthesis and secretion in sheep is still not recognized. As a part of a research dealing with interaction between opioids and steroids, the effect of prolonged administration of progesterone (P4) and opioid receptor agonist or antagonist on the Met-enkephalin synthesis and concentration was examined in sheep brain. Long term P4 treatment significantly decreased the synthesis and the concentration of the opioid peptide in the hypothalamus and pituitary, however, the effect was more pronounced in the hypothalamus. Injections of Met-enkephalin completely or partially reversed the effect of P4. Naltrexone given together with opioid peptide modulated the response to the opioid agonist. The results show that there is an interaction between P4 and endogenous opioids in the central nervous system of cyclic sheep.     

EFFECTS OF 6-HYDROXYDOPAMINE ON CATECHOLAMINE CONTAINING NEURONES IN THE RAT BRAIN

After the intraventricular injection of 6-hydroxydopamine (6-OHDA), there was a long lasting reduction in the brain concentrations of noradrenaline (NA) and dopamine (DA). The brain concentration of NA was affected by lower doses of 6-OHDA than were required to deplete DA. A high dose of 6-OHDA which depleted the brain of NA and DA by 81 per cent and 66 per cent respectively, had no significant effect on brain concentrations of 5-hydroxytryptamine (5-HT) or γ-aminobutyric acid (GABA). The fall in catecholamines was accompanied by a long lasting reduction in the activities of tyrosine hydroxylase and DOPA decarboxylase in the hypothalamus and striatum, areas in the brain which are rich in catecholamine containing nerve endings. There was, however, no consistent effect on catechol-O-methyl transferase or monamine oxidase activity in these brain regions. The initial accumulation of [³H]NA into slices of the hypothalamus and striatum was markedly reduced 22–30 days after 6-OHDA treatment. These results are consistent with the evidence in the peripheral sympathetic nervous system that 6-OHDA causes a selective destruction of adrenergic nerve endings and suggest that this compound may have a similar destructive effect on catecholamine neurones in the CNS.     

Neuro‐Modulation of Immuno‐Endocrine Response Induced by Kaliotoxin of Androctonus Scorpion Venom

Kaliotoxin (KTX), a specific blocker of potassium channels, exerts various toxic effects due to its action on the central nervous system. Its use in experimental model could help the understanding of the cellular and molecular mechanisms involved in the neuropathological processes related to potassium channel dysfunctions. In this study, the ability of KTX to stimulate neuro‐immuno‐endocrine axis was investigated. As results, the intracerebroventricular injection of KTX leads to severe structural–functional alterations of both hypothalamus and thyroid. These alterations were characterized by a massive release of hormones’ markers of thyroid function associated with damaged tissue which was infiltrated by inflammatory cell and an imbalanced redox status. Taken together, these data highlight that KTX is able to modulate the neuro‐endocrine response after binding to its targets leading to the hypothalamus and the thyroid stimulation, probably by inflammatory response activation and the installation of oxidative stress in these organs.     

Functional connections between the tegmentum mesencephali and supraoptico-hypophyseal hypothalamic neurosecretory system in albino rats

Bilateral electrolytic destruction of the paramedian zones of the caudal part of the tegmentum mesencephali caused an increase in the number of neurosecretory cells with low functional activity and the appearance of degenerating forms in the supraoptic nucleus of the hypothalamus (mainly in the medial part of the nucleus, adjacent to the optic chiasma); destruction of individual Herring's bodies was observed in the posterior lobe of the pituitary. The subnormal content of neurosecretory substance in all parts of the supraoptico-hypophyseal neurosecretory system was matched by a low plasma level of vasopressin-antidiuretic hormone. In animals with destructive lesions in the tegmentum mesencephali exposure to nociceptive stimulation activated mainly the neurosecretory cells in the lateral part of the supraoptic nucleus; the loss of neurosecretion from the posterior pituitary was partial; the plasma neurohormone level was much lower than in the control animals after nociceptive stimulation. It is postulated that changes in the response of the supraoptico-hypophyseal system to stress were probably the result of interruption of afferent pathways to the hypothalamus from the tegmentum mesencephali. The result of these experiments suggest that the paramedian zones of the tectum mesencephali exert a modulating influence on the function of this system during stress.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 2, pp. 157–164, March–April, 1977.     

Impaired adaptation of gastrointestinal motility following chronic stress in maternally separated rats

Exposure to early life stress causes increased stress responsiveness and permanent changes in the central nervous system. We recently showed that delayed gastric emptying (GE) and accelerated colonic transit (CT) in response to acute restraint stress (ARS) were completely restored following chronic homotypic stress (CHS) in rats via upregulation of hypothalamic oxytocin (OXT) expression. However, it is unknown whether early life stress affects hypothalamic OXT circuits and gastrointestinal motor function. Neonatal rats were subjected to maternal separation (MS) for 180 min/day for 2 wk. Anxiety-like behaviors were evaluated by the elevated-plus-maze test. GE and CT were measured under nonstressed (NS), ARS, and CHS conditions. Expression of corticotropin-releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real time RT-PCR and immunohistochemistry. MS increased anxiety-like behaviors. ARS delayed GE and accelerated CT in control and MS rats. After CHS, delayed GE and accelerated CT were restored in control, but not MS, rats. CRF mRNA expression was significantly increased in response to ARS in control and MS rats. Increased CRF mRNA expression was still observed following CHS in MS, but not control, rats. In response to CHS, OXT mRNA expression was significantly increased in control, but not MS, rats. The number of OXT-immunoreactive cells was increased following CHS in the magnocellular part of the PVN in control, but not MS, rats. MS impairs the adaptation response of gastrointestinal motility following CHS. The mechanism of the impaired adaptation involves downregulation of OXT and upregulation of CRF in the hypothalamus in MS rats.     

Effects of leucine-enkephalin on hypothalamic-pituitary-thyroid axis in rats

Basal thyrotropin (TSH) levels in plasma and the TSH response to thyrotropin-releasing hormone (TRH) were inhibited after Leucine-enkephalin (L-EK) administration iv in rats. TRH and TSH responses to cold were inhibited after L-EK administration. In the L-DOPA, haloperidol or 5-hydoxytryptophan-treated rats, the inhibitory effect of L-EK on TSH release was restored. Findings suggested that L-EK acted both the hypothalamus and pituitary. Its inhibitory effects on TRH and TSH release at least partially mediated by interaction with amines in the central nervous system.     

Cerebral Cell Renewal in Adult Mice Controls the Onset of Obesity

The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance.     

Role of interleukin-1 in stress responses

Recently, the central roles of interleukin-1 (IL-1) in physical stress responses have been attracting attention. Stress responses have been characterized as central neurohormonal changes, as well as behavioral and physiological changes. Administration of IL-1 has been shown to induce effects comparable to stress-induced changes. IL-1 acts on the brain, especially the hypothalamus, to enhance release of monoamines, such as norepinephrine, dopamine, and serotonin, as well as secretion of corticotropin-releasing hormone (CRH). IL-1-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis in vivo depends on secretion of CRH, an intact pituitary, and the ventral noradrenergic bundle that innervates the CRH-containing neurons in the paraventricular nucleus of the hypothalamus. Recent studies have shown that IL-1 is present within neurons in the brain, suggesting that IL-1 functions in neuronal transmission. We showed that IL-1 in the brain is involved in the stress response, and that stress-induced activation of monoamine release and the HPA axis were inhibited by IL-1 receptor antagonist (IL-1Ra) administration directly into the rat hypothalamus. IL-1Ra has been known to exert a blocking effect on IL-1 by competitively inhibiting the binding of IL-1 to IL-1 receptors. In the latter part of this review, we will attempt to describe the relationship between central nervous system diseases, including psychological disorders, and the functions of IL-1 as a putative neurotransmitter.     

Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response

Inhaled pollutants produce effects in virtually all organ systems in our body and have been linked to chronic diseases including hypertension, atherosclerosis, Alzheimer's and diabetes. A neurohormonal stress response (referred to here as a systemic response produced by activation of the sympathetic nervous system and hypothalamus–pituitary–adrenal (HPA)-axis) has been implicated in a variety of psychological and physical stresses, which involves immune and metabolic homeostatic mechanisms affecting all organs in the body. In this review, we provide new evidence for the involvement of this well-characterized neurohormonal stress response in mediating systemic and pulmonary effects of a prototypic air pollutant — ozone. A plethora of systemic metabolic and immune effects are induced in animals exposed to inhaled pollutants, which could result from increased circulating stress hormones. The release of adrenal-derived stress hormones in response to ozone exposure not only mediates systemic immune and metabolic responses, but by doing so, also modulates pulmonary injury and inflammation. With recurring pollutant exposures, these effects can contribute to multi-organ chronic conditions associated with air pollution. This review will cover, 1) the potential mechanisms by which air pollutants can initiate the relay of signals from respiratory tract to brain through trigeminal and vagus nerves, and activate stress responsive regions including hypothalamus; and 2) the contribution of sympathetic and HPA-axis activation in mediating systemic homeostatic metabolic and immune effects of ozone in various organs. The potential contribution of chronic environmental stress in cardiovascular, neurological, reproductive and metabolic diseases, and the knowledge gaps are also discussed. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.     

抗体应答期间大鼠脑和胸腺中儿茶酚胺含量的变化

目的：探讨在抗体应答期间,脑和淋巴器官中儿茶酚胺（ＣＡｓ）含量的动态变化,籍以了解免疫状态对中枢和外周ＣＡｓ神经活动的影响。方法：用绵羊红细胞（ＳＲＢＣ）免疫大鼠,在免疫后第２￣７ｄ应用高效液相色谱－电化学检测法（ＨＰＬＣ－ＥＣＤ）测定大鼠下丘脑、海马、脑干和胸腺中云甲肾上腺素（ＮＡ）、肾上腺素（Ａ）、多巴胺（ＤＡ）和高香草酸（ＨＶＡ）的含量。结果：①下且脑和海马内ＮＡ在抗体应答期间升高,而胸腺中     

Brain corticotropin-releasing factor acts as inhibitor of stress-induced gastric erosion in rats

Gastric lesions are known to be caused by stress. Corticotropin-releasing factor (CRF) is a key peptide initiating various stress response. This study was designed to investigate how brain CRF is involved in the occurrence of stress-induced gastric erosion in rats. Intracerebroventricular (icv) administration of CRF suppressed the occurrence of gastric erosion induced by water-immersion restraint stress, and its suppressive effect was blocked by coadministration of a CRF receptor antagonist in rats. The peripheral administration of CRF had no influence on the occurrence of erosion. The icv administration of a CRF receptor antagonist or anti-rat CRF gamma-globulin increased gastric erosion induced by the stress. Ganglionic blockade with chlorisondamine, muscarinic blockade with atropine, or bilateral adrenalectomy by itself significantly inhibited the occurrence of stress-induced gastric erosion, and no additional effect of CRF on these treatments-induced inhibition of erosion was found. These results, therefore, suggest that the occurrence of stress-induced gastric erosion is mediated by the autonomic nervous system- and adrenal-dependent pathway, and that brain CRF reduces the occurrence of stress-induced gastric lesions by acting on its specific receptor within the central nervous system, probably through the autonomic nervous system- and adrenal-dependent mechanism.     

Brain angiotensin receptors and adaptation to stress

In this short review, we hypothesize that the central renin-angiotensin system might participate to the initiation of compensatory responses to a stressor agent. Regulation of the expression of the brain angiotensin receptors might constitute a primary molecular mechanism by which this protecting action would take place. We illustrate this possibility by investigating the expression of the angiotensin type 1 receptor in the hypothalamus in response to systemic and neurogenic stressors.