Ghrelin and reproductive disorders

Ghrelin is an important factor involved in most of the metabolic and hormonal signals which adapt the reproductive functions in conditions of altered energy balance. Moreover, the coordinated role of leptin and ghrelin appears in fact to have a specific role in the regulation of puberty. Systemic action of ghrelin on the reproductive axis involves the control of the hypothalamic-pituitary-gondal axis. In addition, it has been shown that ghrelin may directly act at a gonadal level in both females and males. Available data also demonstrate that sex steroid hormones and gonadotropins may in turn regulate the gonadal effect of ghrelin, as documented by studies performed in females with the polycystic ovary syndrome and in hypogonadal men. Notably, recent studies also confirm a potentially important role for ghrelin in fetal and neonatal energy balance, and specifically in allowing fetal adaptation to an adverse intrauterine environment.     

Immunohistochemical analysis of the early ontogeny of the neuropeptide Y system in rat brain

The distribution of neuropeptide Y in the developing rat brain was studied with immunocytochemistry, using the peroxidase-antiperoxidase method. Immunoreactive perikarya were first seen on embryonic day 13 and staining of fibres appeared from embryonic day 15 onwards: perikaryal staining was generally more intense prenatally than after birth. Areas rich in neuropeptide Y immunostaining included the monoaminergic regions of the brain stem from embryonic day 13 (especially the lateral reticular nucleus and the medullary reticular formation), the dorsal mesencephalon (with spots of immunoreactivity in the outer subventricular zone at embryonic days 13 or 14 and many cells and fibres in the inferior colliculus from embryonic days 16-20) and the olfactory tubercle/ventral striatum from embryonic day 15 until birth. The period of development of cortical neurones extended from embryonic day 19 until postnatal day 21. A hitherto unreported feature unique to neuropeptide Y was the presence in certain parts of the cerebral cortex of transient cells at the base of the cortical plate bearing radial processes which transverse its width. They were present from embryonic day 17 until postnatal day 4 and were maximally developed at embryonic days 20 or 21, contributing at this age a substantial fibre projection through the immature corpus callosum. The abundance of neuropeptide Y in the prenatal rat brain suggests it may play an important role in development.     

Human fetal brain cells in aggregate culture: A model system to study regulatory processes of the developing human neuropeptide Y (NPY)-producing neuron

Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the brain and it has been implicated in a wide range of brain functions, including mentation. The aim of this study was to establish a culture system of human fetal brain cells expressing NPY in a regulated manner. The NPY production in response to forskolin and phorbol 12-myristate 13-acetate (PMA) was taken as a criterion for regulated expression of NPY. Aggregates were formed from dissociated cells derived from the cerebral hemispheres of human fetuses (12.5–19 weeks' gestation) by constant rotation and were maintained in serum-free medium. A 24 hr exposure to 10 μM forskolin + 20 nM PMA led to a 2–6-fold increase in NPY content of the cultures, most of which (80–90%) was secreted into the medium. The latter consisted of two substances differing in size: one corresponding in size to proNPY and the other to NPY. Thus, forskolin + PMA led to an increased production of NPY. Exposure to PMA alone led to an increase in NPY production comparable to that seen after forskolin + PMA and this effect of PMA was dose-dependent. In contrast, forskolin alone did not induce NPY production. Conditioned medium, derived from monolayer cultures enriched with human astrocytes, enhanced NPY production in response to forskolin + PMA in an age-dependent manner. The NPY production by aggregates derived from a 12.5-week-, 14-week- and 18-week-old fetus was enhanced 3-3.6-fold, 1.6-2-fold and 1.1-fold, respectively. Thus, expression of the NPY neurons in this culture system is a regulated process. The NPY production is enhanced markedly by activation of the protein kinase C pathway and by an astrocyte-derived soluble substance(s). Based on these results, we propose that this culture system can serve as a model for the study of regulatory processes of the human developing NPY neuron.     

CART peptides in the central control of feeding and interactions with neuropeptide Y

While CART peptides have been implicated as novel, putative peptide neurotransmitters/cotransmitters, behavioral effects of these peptides have not yet been demonstrated. In this study, we show the first behavioral effect of CART peptides. Icv administration of CART peptide fragments inhibits feeding in rats. Moreover, injection of an antibody to CART peptide 82–103 stimulates feeding, suggesting that endogenous CART peptides exert an inhibitory tone on feeding. Injection of CART peptide 82–103 five min before NPY reduces the increase in feeding caused by injection of NPY alone. Also, in light microscopic immunohistochemical studies, NPY-positive varicosities were observed around CART peptide-positive cell bodies in the paraventricular nucleus of the hypothalamus. These data suggest functional interactions between CART peptides and NPY. These results indicate that CART peptides play a role in the control of food intake by the brain. Synapse 29:293–298, 1998. © 1998 Wiley-Liss, Inc.     

RANK deletion in neuropeptide Y neurones attenuates oestrogen deficiency‐related bone loss

The RANKL pathway is known to be an important aspect of the pathogenesis of oestrogen deficiency‐induced bone loss. RANK deletion specifically in neuropeptide Y (NPY) neurones has been shown to enhance the ability of the skeleton to match increases in body weight caused by high‐fat diet feeding, likely via the modulation of NPY levels. In the present study, we used ovariectomy in female mice to show that RANK deletion in NPY neurones attenuates bone loss caused by long‐term oestrogen deficiency, particularly in the vertebral compartment. Ovariectomy led to a reduction in NPY expression levels in the arcuate nucleus of NPY^cre/+;RANK^lox/lox mice compared to NPY^cre/+;RANK^lox/+ controls. Because NPY deficient mice also displayed a similar protection against ovariectomy‐induced bone loss, modulation of hypothalamic NPY signalling is the likely mechanism behind the protection from bone loss in the NPY^cre/+;RANK^lox/lox mice.     

The C-terminal flanking peptide of neuropeptide Y (NPY) is not essential for seizure-suppressant actions of prepro-NPY overexpression in male rats

The full coding sequence of neuropeptide Y (NPY), prepro-NPY, is sequentially metabolized into three peptides; an N-terminus 28-amino acid signaling peptide, the NPY peptide itself (NPY1-36), and a 30-amino acid C-terminus peptide, known as the C-terminal flanking peptide of neuropeptide-Y (CPON). While the signaling peptide directs intracellular trafficking and NPY1-36 is well characterized, the biological function of CPON is unknown. This is noteworthy because CPON is co-stored and co-released along with NPY1-36 and could thus potentially serve important functions. To assess the role of CPON, we adapted a viral genetic approach using two different vector designs encoding NPY, but where the CPON coding sequence was excluded from one of the vectors. Thus, the effect of CPON was indirectly assessed. Male rats received intrahippocampal injections of either a vector encoding NPY1-39 whose metabolism yields NPY1-36 and not CPON, or a prepro-NPY vector encoding both NPY1-36 and CPON. A third vector encoding EGFP served as control. We subsequently studied to what extent CPON might affect seizure susceptibility and memory performance, respectively, to address two important questions to evaluate the potential of NPY gene therapy in epilepsy. Both NPY vectors, as compared to EGFP control, were found to be equally effective at suppressing acute kainate–induced seizures, and both did not influence learning and memory performance in the Morris water maze. Thus CPON itself does not appear to aid actions governed by vector–mediated overexpression of NPY1-36 within the hippocampus. Whether CPON serves other important functions remains to be determined.     

Neuropeptide Y (NPY) and NPY Y1 receptor in periodontal health and disease

Objectives

Neuropeptide Y (NPY) coordinates inflammation and bone metabolism which are central to the pathogenesis of periodontitis. The present study was designed to determine whether NPY was quantifiable in human gingival crevicular fluid (GCF) and to test the null hypothesis that GCF levels of NPY were the same in periodontal health and disease. A subsidiary aim was to determine the potential functionality of released NPY by detecting the presence of NPY Y1 receptors in gingival tissue.

Design

The periodontitis group consisted of 20 subjects (10 females and 10 males) mean age 41.4 (S.D. 9.6 years). The control group comprised 20 subjects (10 females and 10 males) mean age 37.4 (S.D. 11.7 years). NPY levels in GCF were measured in periodontal health and disease by radioimmunoassay. NPY Y1 receptor expression in gingival tissue was determined by Western blotting of membrane protein extracts from healthy and inflamed gum.

Results

Healthy sites from control subjects had significantly higher levels of NPY than diseased sites from periodontitis subjects. NPY Y1 receptor protein was detected in both healthy and inflamed gingival tissue by Western blotting.

Conclusions

The significantly elevated levels of NPY in GCF from healthy compared with periodontitis sites suggests a tonic role for NPY, the functionality of which is indicated by the presence of NPY Y1 receptors in local gingival tissue.     

Prolonged chronic ethanol exposure alters neuropeptide Y and corticotropin-releasing factor levels in the brain of adult Wistar rats

There is evidence to suggest that alterations in neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) contribute to the escalated voluntary ethanol intake seen following long term chronic ethanol exposure. The present study assessed whether the duration of chronic ethanol exposure and abstinence alters brain levels of NPY and CRF in adult Wistar rats. NPY-like immunoreactivity (NPY-LI) and CRF-LI were determined in the amygdala (AMYG), frontal cortex (FCTX), hippocampus (HPC) and parietal cortex (PCTX) of adult Wistar rats after chronic ethanol exposure, and 24-h and 2-weeks following withdrawal (WD). Chronic ethanol exposure consisted of either a 2-week or an 8-week ethanol vapor regimen. No change in brain levels of NPY-LI, CRF-LI and the NPY-LI/CRF-LI ratio was observed 2-weeks following ethanol exposure, whereas, 8-weeks of ethanol exposure produced a significant effect on NPY-LI expression in the AMYG and FCTX. Moreover, an 8-week ethanol vapor regimen significantly increased CRF-LI levels in the HPC and PCTX. Findings from the present study suggest that a longer duration of ethanol vapor, similar to what is required to enhance voluntary drinking, is required to produce changes in NPY-LI and CRF-LI expression in the adult rat brain.     

脉络宁对COPD患者NPY含量的变化观察

目的:探讨脉络宁对慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)患者血清神经肽(neuro-peptide Y,NPY)含量变化的影响.方法:选择40例应用脉络宁治疗的COPD患者为观察组;另选未用脉络宁治疗的30例COPD患者为对照组.观察组患者在用脉络宁治疗前...     

白癜风进展期患者皮肤疱液中NPY、sICAM-1、IL-12和GM-CSF水平变化的实验研究

目的:探讨白癜风病患者的发病、进展与免疫学机制的关系.方法:将确诊为进展期白癜风的80例患者分为寻常型(54例),节段型(26例)组.各以白斑处和非白斑处2组的疱液中的研究指标水平进行比较.疱液NPY和GM-CSF采用RIA;IL-12、sICAM-1水平均采用ELISA.结果:本文测定的患者疱液NPY水平显示,寻常型...