Blood borne hormones in a cross-talk between peripheral and brain mechanisms regulating blood pressure,the role of circumventricular organs

Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood–brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified.     

Age-related central regulation of orexin and NPY in the short-lived African killifish Nothobranchius furzeri

Orexin A (OXA) and neuropeptide Y (NPY) are two hypothalamic neuropeptides involved in the regulation of feeding behavior and food intake in all vertebrates. Accumulating evidences document that they undergo age-related modifications, with consequences on metabolism, sleep/wake disorders and progression of neurodegenerations. The present study addressed the age related changes in expression and distribution of orexin A (its precursor is also known as hypocretin—HCRT) and NPY, and their regulation by food intake in the short-lived vertebrate model Nothobranchius furzeri. Our experiments, conducted on male specimens, show that: (a) HCRT and OXA and NPY mRNA and protein are localized in neurons of diencephalon and optic tectum, as well as in numerous fibers projecting through the entire neuroaxis, and are colocalized in specific nuclei; (b) in course of aging, HCRT and NPY expressing neurons are localized also in telencephalon and rhombencephalon; (c) HCRT expressing neurons increased slightly in the diencephalic area of old animals and in fasted animals, whereas NPY increased sharply; (d) central HCRT levels are not regulated neither in course of aging nor by food intake; and (e) central NPY levels are augmented in course of aging, and regulated by food intake only in young. These findings represent a great novelty in the study of central orexinergic and NPY-ergic systems in vertebrates', demonstrating an uncommon and unprecedented described regulation of these two orexigenic neuropeptides.     

The Medial Amygdala Modulates Body Weight but not Neuroendocrine Responses to Chronic Stress

Stress pathologies such as depression and eating disorders (i.e. anorexia nervosa) are associated with amygdalar dysfunction, which are linked with hypothalamic-pituitary-adrenal axis (HPA) axis hyperactivity. The medial amygdaloid nucleus (MeA), a key output nucleus of the amygdaloid complex, promotes HPA axis activation to acute psychogenic stress and is in a prime position to mediate the deleterious effects of chronic stress on physiology and behaviour. The present study tests the hypothesis that the MeA is necessary for the development of maladaptive physiological changes caused by prolonged stress exposure. Male rats received bilateral ibotenate or sham lesions targeting the MeA and one half underwent 2 weeks of chronic variable stress (CVS) or served as home cage controls. Sixteen hours post CVS, all animals were exposed to an acute restraint challenge. CVS induced thymic involution, adrenal hypertrophy, and attenuated body weight gain and up-regulation of hypothalamic corticotrophin-releasing hormone mRNA expression. Consistent with previous literature, lesions of the MeA dampened stress-induced increases in corticosterone after 30 min of exposure to acute restraint stress. However, this effect was independent of CVS exposure, suggesting that the MeA may not be critical for modulating neuroendocrine responses after chronic HPA axis drive. Interestingly, lesion of the MeA modestly exaggerated the stress-induced attenuation of weight gain. Overall, the data obtained suggest that the MeA modulates the neuroendocrine responses to acute but not chronic stress. In addition, the data suggest that the MeA may be an important neural component for the control of body weight in the face of chronic stress.     

Nefazodone Alters NPY Immunostaining in Rat Arcuate-paraventricular Projection without Changes in Food Intake and Body Weight

Abstract

Nefazodone is an antidepressant drug that inhibits serotonin and noradrenaline reuptake. The aim of the present work was to study the effects of nefazodone on food intake, body weight, adiposity and hypothalamic NPY immunostaining in rats. For this purpose, male Sprague-Dawley rats (3-month-old) were administered with nefazodone (20 mg/kg; i.p) daily for two weeks. The control group was given 0.9% NaCl solution. Hypothalamic arcuate, paraventricular, periventricular, supraoptic and suprachiasmatic nuclei and the lateral hypothalamic area were immunostained for NPY. Chronic nefazodone administration in rats did not modify food intake, body weight and adipose depot size (subcutaneous, perirenal and epidydimal white adipose tissues, and interscapular brown adipose tissue). However, a significant decrease in paraventricular NPY immunostaining was found in the nefazodone group compared with the control group. No changes in other hypothalamic regions such as arcuate, periventricular, supraoptic and suprachiasmatic nuclei, and lateral and medial preoptic areas were observed. Because nefazodone is an α₁-adrenoceptor antagonist, it can be proposed that the expected decrease in food intake after nefazodone administration, due to its effects on NPY arcuate-paraventricular projection, could be masked by the opposite orexigenic effect of α₁-adrenoceptor blockade.     

针刺对便秘型肠易激综合征患者血浆5-HT、NPY和CGRP的影响

目的?观察针刺对便秘型肠易激综合征（IBS-C）患者血浆中5-羟色胺（5-HT）、神经肽Y（NPY）和降钙素基因相关肽（CGRP）水平的影响,从脑-肠轴的角度阐述针刺治疗IBS-C的效应机制。方法?60例IBS-C患者随机分为针刺组和西药组。针刺组30例,予针刺治疗,取天枢、足三里、上巨虚、太冲、三阴交、印堂、百会,每日1次,每周5次,4周为1个疗程;西药组30例,予口服乳果糖口服溶液,15?mL每次,每日3次,4周为1个疗程。观察2组治疗前后临床症状改善情况。同时采集2组患者治疗前后及30名健康志愿者外周静脉血,采用Elisa法检测患者血浆中的5-HT、CGRP和NPY的水平,探讨针刺对IBS-C患者血浆5-HT、NPY和CGRP的影响。结果?①针刺及西药均能显著改善IBS-C患者的临床症状（P<0.01）,针刺组疗效均优于西药组（P<0.01）。②2组IBS-C患者血浆5-HT、NPY和CGRP水平均明显高于健康志愿者,差异有统计学意义（P<0.01）。治疗后2组IBS-C患者血浆5-HT、NPY和CGRP水平均下降,针刺组患者血浆5-HT、NPY和CGRP水平较治疗前有显著差异（P<0.01）;西药组患者血浆5-HT、NPY水平较治疗前也有显著差异（P<0.01）,CGRP水平与治疗前比较无统计学意义（P>0.05）。2组治疗后组间比较血浆5-HT、NPY无统计学差异（P>0.05）,血浆CGRP有统计学差异（P<0.01）,针刺组下降趋势优于西药组。结论?①针刺可显著改善IBS-C患者的临床症状,疗效均优于西药组。②IBS-C患者血浆5-HT、NPY和CGRP水平均升高,说明脑肠肽水平异常与IBS-C症状密切相关。③针刺能明显降低患者血浆5-HT、NPY和CGRP水平,缓解腹痛与腹部不适程度,表明针刺对IBS-C患者血浆脑肠肽水平的良性调控作用可能是其治疗本病的效应机制之一。      

The effects of a standardized Acanthopanax koreanum extract on stress-induced behavioral alterations in mice

Ethnopharmacological relevance

The roots and stem bark of Acanthopanax koreanum Nakai (Araliaceae), a well-known herbal medicine in Jeju Island, Korea, has been used as a tonic agent in treating stress-related states. Despite its popular application, the anti-anxiety or anti-depressive action of Acanthopanax koreanum is not yet known.

Aim of the study

This study aimed to determine the effects of Acanthopanax koreanum on stress-induced behavioral alterations such as anxiety and depression.

Materials and methods

Mice in the acute stress group were exposed to immobilization stress for 2 h followed by electric foot shocks (0.5 mA in 1 s duration with a 10 s inter-shock interval) for 2 min, while sub-chronically stressed mice were exposed to these stresses for 2 weeks, once per day. 70% ethanolic extract of Acanthopanax koreanum (EEAK) (25, 50, 100, or 200 mg/kg) was administered once or sub-chronically (for 2 weeks) 1 h prior to stress induction. Anxiety- or depression-like behavioral changes were evaluated using the elevated plus-maze (EPM) test and the forced swimming test (FST) a day after the final stress induction. Corticosterone levels and spleen weight were measured after conducting all the behavioral assays. The numbers of BrdU- or DCX-immunopositive cells in the hippocampal region of sub-chronically stressed mice were measured 2 days after EEAK treatment.

Results

The percentage of time spent in the open arms was decreased in both the acutely and chronically stressed mice. In the FST, the immobility time was increased by only chronic stress, but not by acute stress. Acute or sub-chronic administration of EEAK significantly prevented the anxiety- or depression-like behavioral changes caused by stress. EEAK also attenuated stress-induced decrease and increase of spleen weight and corticosterone levels, respectively. Furthermore, the sub-chronic administration of EEAK (100 or 200 mg/kg, for 2 weeks) increased the number of BrdU-, doublecortin-, and neuropeptide Y-positive cells in the hippocampal region of the sub-chronically stressed mice.

Conclusion

EEAK attenuated the behavioral and biochemical changes in acute or sub-chronic stressed mice. These results suggest the therapeutic potential of Acanthopanax koreanum for the treatment of stress-related neuropsychiatric disorders including anxiety disorders or major depressive disorder.     

NPY and NPY receptors in airway structural and inflammatory cells in allergic asthma

Purpose

Neuropeptide Y (NPY) level is elevated in allergic asthmatic airways and activation of NPY receptor-1 (NPY-Y1) on antigen‐presenting cells (APCs) is essential for T cell priming. Paradoxically, NPY-Y1 modulates hyper-responsiveness in T cells, suggesting a bimodal role for NPY in APCs and T cells. Therefore, determination of the temporal and spatial expression pattern of NPY and its receptors in asthmatic airways is essential to further understand the role of NPY in allergic asthma.

Methods

Lungs were isolated from control and acute and chronic stages of OVA-sensitized and challenged mice (OVA). Stains, including H&E, PAS, and trichrome, were used to determine the severity of lung pathology. The expression patterns of NPY and NPY-Y receptors in the airways were determined using ELISA and immunofluorescence. Cytokine levels in the BALF were also measured.

Results

NPY levels were undetectable in the BALF of control mice, but significantly increased in the OVA group at day 80. Levels of IL-4, TGF-β1 and TGF-β2, significantly increased and peaked on day 45 and decreased on day 80 in the OVA group, exhibiting an inverse correlation with NPY levels. NPY expression was localized to macrophage-like cells in the peri-bronchial and peri-vascular areas in the lung tissue. NPY-Y1 and -Y5 receptors were constitutively expressed by both structural and inflammatory cells in the lung tissue.

Conclusions

NPY produced by activated macrophage-like cells may be involved in regulating cytokine production and cellular activities of immune cells in asthma. However, it remains unclear whether such an increase in NPY is a defensive/compensatory mechanism to modulate the effects of inflammatory cytokines.