Autonomic nerves and perivascular fat: Interactive mechanisms

The evidence describing the autonomic innervation of body fat is reviewed with a particular focus on the role of the sympathetic neurotransmitters. In compiling the evidence, a strong case emerges for the interaction between autonomic nerves and perivascular adipose tissue (PVAT). Adipocytes have been shown to express receptors for neurotransmitters released from nearby sympathetic varicosities such as adrenoceptors (ARs), purinoceptors and receptors for neuropeptide Y (NPY). Noradrenaline can modulate both lipolysis (via α₂- and β₃-ARs) and lipogenesis (via α₁- and β₃-ARs). ATP can inhibit lipolysis (via P₁ purinoceptors) or stimulate lipolysis (via P_2y purinoceptors). NPY, which can be produced by adipocytes and sympathetic nerves, inhibits lipolysis. Thus the sympathetic triad of transmitters can influence adipocyte free fatty acid (FFA) content. Substance P (SP) released from sensory nerves has also been shown to promote lipolysis. Therefore, we propose a mechanism whereby sympathetic neurotransmission can simultaneously activate smooth muscle cells in the tunica media to cause vasoconstriction and alter FFA content and release from adjacent adipocytes in PVAT. The released FFA can influence endothelial function. Adipocytes also release a range of vasoactive substances, both relaxing and contractile factors, including adiponectin and reactive oxygen species. The action of adipokines (such as adiponectin) and reactive oxygen species (ROS) on cells of the vascular adventitia and nerves has yet to be fully elucidated. We hypothesise a strong link between PVAT and autonomic fibres and suggest that this poorly understood relationship is extremely important for normal vascular function and warrants a detailed study.     

Immunolocalization of neurotransmitter-synthesizing enzymes and neuropeptides with associated receptors in the photophores of the hatchetfish, Argyropelecus hemigymnus Cocco, 1829

Anatomical and functional studies of the autonomic innervation of the photophores of luminescent fishes are scarce. The present immunohistochemical study demonstrated the presence of nerve fibers in the luminous epithelium and lens epithelium of the photophores of the hatchet fish, Argyropelecus hemigymnus and identified the immunoreactive elements of this innervation. Phenylethanolanine N-methyltransferase (PNMT) and catecholamine (CA)-synthesizing enzymes were detected in nerve varicosities inside the two epithelia. Neuropeptides were localized in neuropeptide Y (NPY) and substance P (SP)- and its NK11 receptor-immunopositive nerves in the lens epithelium. Neuropeptides were also localized in non-neural cell types such as the lens cells, which displayed immunoreactivities for pituitary adenylate cyclase activating peptide (PACAP) and their receptors R-12 and 93093-3. This reflects the ability of the neuropeptide-containing nerves and lens cells to turn on and off the expression of selected messengers. It appears that the neuropeptide-containing nerves demonstrated in this study may be sensory. Furthermore, neuronal nitric oxide synthase-immunopositive axons associated with photocytes in the luminous epithelium have previously been described in this species. Whereas it is clear that the photophores receive efferent (motor) fibers of spinal sympathetic origin, the origin of the neuropeptide sensory innervation remains to be determined. The functional roles of the above neuropeptides or their effects on the bioluminescence or the chemical nature of the terminals, either sensory or postganglionic neurons innervating the photophores, are still not known.     

手足口病并发脑干脑炎患儿血清NPY、Hcy和S100β测定的临床意义

目的：探讨手足口病并发脑干脑炎患儿NPY、Hcy和S100β水平的变化及临床意义。方法：应用放射免疫分析、免疫化学法和酶联法对32例手足口病并发脑干脑炎患儿进行了血清NPY、Hcy和S100β检测,并与35例正常健康儿进行比较。结果：手足口病患儿血清NPY、Hcy和S100β水平均非常显著地高于正常儿组（P〈0.01）,且血清NPY水平与Hcy和S100β水平呈正相关（r=0.4812、0.5984,P〈0.01）。结论：检测手足口病并发脑干脑炎患儿NPY、Hcy和S100β水平,对判断病情和评价疗效均有重要的临床价值。     

阿尔茨海默病大鼠海马区、大肠区脑肠肽NPYmRNA表达水平及其关联的研究

目的:研究AD大鼠大肠区、海马区脑肠肽NPYmRNA表达水平及其关联,探讨脾脑相关理论的微观机制。方法:运用右侧海马注射凝聚态Aβ1-40的方法制作AD大鼠模型,采用半定量RT-PCR法检测比较假手术组和模型对照组药物大鼠海马区、大肠区脑肠肽NPYmRNA的表达水平。结论:AD大鼠海马区、大肠区脑肠肽NPYmRNA表达水平均降低。脾脑相关理论的微观机制可能与NPY有关。     

The responses of hypothalamic NPY and OBRb mRNA expression to food deprivation develop during the neonatal-prepubertal period and exhibit gender differences in rats

Neuropeptide Y (NPY) is an important hypothalamic orexigenic neuropeptide that acts in the brain. It has been established that the fasting-induced up-regulation of NPY expression is mainly caused by a reduction in the activity of leptin, which is a hormone secreted by adipose tissue. We have reported that in female rats hypothalamic NPY mRNA expression does not respond to fasting during the early neonatal period, but subsequently becomes sensitive to it later in the neonatal period. In this study, we compared the developmental changes in the responses of NPY and leptin expression to fasting between male and female rats during the neonatal to pre-pubertal period. Fasting was induced by maternal deprivation during the pre-weaning period (postnatal days 10 and 20) and by food deprivation during the post-weaning period (postnatal day 30). Hypothalamic NPY mRNA expression was not affected by fasting on postnatal day 10, whereas it was increased by fasting on postnatal day 20 and 30 in both males and females. On the other hand, the serum leptin level was decreased by fasting at all examined ages in both sexes. Namely, hypothalamic NPY mRNA expression was not correlated with the reduction in the serum leptin level at postnatal day 10 in either sex. Under the fasted conditions, the hypothalamic NPY mRNA levels of the males were higher than those of the females on postnatal days 20 and 30, whereas no such differences were observed under the normal nourishment conditions. The serum leptin levels observed under the fasted conditions did not differ between males and females at any examined age. These results suggest that some hypothalamic NPY functions develop during the neonatal period and that there is no major difference between the sexes with regard to the time when NPY neurons become sensitive to fasting. They also indicate that hypothalamic NPY expression is more sensitive to under-nutrition in male rats than in female rats, at least during the pre-pubertal period.     

The neuropeptide Y antagonist PYX2 decreases lordosis behavior

Neuropeptide Y (NPY) has been localized to noradrenergic neurons and both the noradrenergic system and NPY play a facilitatory role in the control of luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH) release. The present experiments examined whether NPY also plays a role in the control of lordosis. Adult female guinea pigs were ovariectomized (ovx) and implanted with a cannula into the lateral ventricle. In Experiment 1, intracerebroventricular (ICV) administration of the NPY antagonist PYX2 (0, 0.5, 2.0 or 10.0 μg) caused a dose-dependent decrease in lordosis behavior in ovx, estrogen and progesterone-primed guinea pigs. In addition to an effect on the mean lordosis response, PYX2 also decreased the percent of animals showing lordosis and the maximum lordosis response. In Experiment 2, NPY administration (25 μg, ICV) 30 min after PYX2 (2 μg, ICV) to ovx estrogen and progesterone-primed females significantly reversed the effect of the PYX2. Because the NPY antagonist PYX2 reversibly decreased lordosis behavior this suggests that NPY plays a facilitatory role in the control of lordosis behavior.     

Effects of scorpion venom heat-resistant peptide on the hippocampal neurons of kainic acid-induced epileptic rats

Scorpion venom is a Chinese medicine for epilepsy treatment, but the underlying mechanism is not clear. Scorpion venom heat-resistant peptide (SVHRP), a peptide isolated from the venom of Buthus martensii Karsch, has an anti-epileptic effect by reducing seizure behavior according to a modified Racine scale. The present study aimed to investigate the molecular mechanism of SVHRP on temporal lobe epilepsy. The hippocampus and hippocampal neurons from kainic acid-induced epileptic rats were treated with SVHRP at different doses and duration. Quantitative RT-PCR and immunoblotting were used to detect the expression level of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), cAMP-response element binding protein (CREB), stromal interaction molecule (STIM), and calcium release-activated calcium channel protein 1 (ORAI1). In the hippocampal tissues and primary hippocampal neuron cultures, SVHRP treatment resulted in increased mRNA and protein levels of BDNF and NPY under the epileptic condition. The upregulation of BDNF and NPY expression was positively correlated with the dose level and treatment duration of SVHRP in hippocampal tissues from kainic acid-induced epileptic rats. On the other hand, no significant changes in the levels of CREB, STIM, or ORAI1 were observed. SVHRP may exhibit an anti-epileptic effect by upregulating the expression of BDNF and NPY in the epileptic hippocampus.     

Paradoxical Effect of Gonadotrophin‐Inhibiting Hormone to Negatively Regulate Neuropeptide Y Neurones in Mouse Arcuate Nucleus

Regulation of reproduction and energy homeostasis are linked, although our understanding of the central neural mechanisms subserving this connection is incomplete. Gonadotrophin‐inhibiting hormone (GnIH) is a neuropeptide that negatively regulates reproduction and stimulates food intake. Neuropeptide Y (NPY) and products of the pro‐opiomelanocortin (POMC) precursor (β‐endorphin melanocortins) are appetite regulating peptides produced in the neurones of the arcuate nucleus; these peptides also regulate reproduction. In the present study, we determined the effects of GnIH on NPY and POMC neurones. Using brain slices from mice with transgenes for fluorescent tags in the two types of neurone and patch clamp electrophysiology, a predominant inhibitory effect of GnIH was observed. GnIH (100 nm ) inhibited the firing rate in POMC cells, confirming the results of previous studies and consistent with the stimulatory effect of GnIH on food intake. Paradoxically (i.e. because both GnIH and NPY stimulate food intake), GnIH also had a predominantly inhibitory effect on action potential activity in NPY cells. GnIH also inhibited the secretion of NPY and α‐melanocyte‐stimulating hormone secretion in incubated hypothalamic blocks. GnIH (100 ng) injected into the cerebral ventricles of mice did not increase the number of NPY cells that were positively immunostained for c‐Fos. Finally, dual label immunocytochemistry showed that 20% of NPY neurones had close contacts from GnIH fibres/varicosities. In conclusion, we confirm a negative effect of GnIH on POMC cells and demonstrate a paradoxical reduction of electrophysiological and functional activity in NPY cells.     

妊高征患者血浆神经肽Y水平变化及与妊高征发病的相关性探讨

目的：探讨妊娠期高血压综合征（简称妊高征）患者血浆神经肽Y（NPY）水平的变化及其与妊高征发病的关系。方法：入选我院2013年6月~2014年6月收治的80例妊高征孕妇作为观察对象,分别于产前和产后检测NPY水平,并与同期26例健康孕妇作比较,将观察组80例妊高征孕妇按照病情程度分为轻度妊高征组32例,中度妊高征组28例和重度妊高征组20例,比较产前和产后NPY水平,分析NPY水平变化与妊高征发病的关系。结果：观察组产前NPY水平[（165.6±70.2）ng/L]显著高于对照组[（89.5±13.4）ng/L],产后[（89.3±14.5）ng/L]显著低于产前,差异均具有统计学意义（P均〈0.05）;轻度组产前NPY水平[（90.3±16.5）ng/L]显著低于中度组[（155.5±18.2）ng/L]和重度组[（240.2±30.8）ng/L],中度组也显著低于重度组,3组产后均显著低于产前,且轻度组产后[（80.7±12.0）ng/L]和中度组产后[（82.1±13.5）ng/L]均显著低于重度组[（130.4±32.2）ng/L],差异均具有统计学意义（P均〈0.05）。结论：妊高征患者产前NPY水平升高,并可预测妊高征的发生和发展。