Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP

Recently, hippocampal neuropeptide Y (NPY) gene therapy has been shown to effectively suppress both acute and chronic seizures in animal model of epilepsy, thus representing a promising novel antiepileptic treatment strategy, particularly for patients with intractable mesial temporal lobe epilepsy (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY gene therapy.Here we report how rAAV vector-mediated overexpression of NPY in the hippocampus affects rapid kindling, and subsequently explore how synaptic plasticity and transmission is affected by kindling and NPY overexpression by field recordings in CA1 stratum radiatum of brain slices. In animals injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected by rAAV-NPY treatment, and may be considered less critical for clinical application in epilepsy patients already experiencing memory disturbances.     

肾衰养真胶囊对慢性肾衰竭营养不良大鼠下丘脑神经肽Y mRNA及原阿片黑皮素mRNA表达的影响

目的 观察肾衰养真胶囊对慢性肾衰竭 (CRF) 营养不良大鼠下丘脑神经肽 Y (NPY) mRNA 及原阿片黑皮素 (POMC) mRNA 的表达及其营养状态的影响。方法 采用含 0.5% 腺嘌呤及 4% 酪蛋白饲料联合喂养的方法制作 CRF 营养不良大鼠模型,观察其营养不良发生时间,符合 CRF 营养不良模型的随机分为模型组、肾衰养真胶囊组和开同组。治疗4周后,检测下丘脑 NPY mRNA 和 POMC mRNA 表达水平。结果 肾衰养真胶囊组大鼠营养状况明显改善,下丘脑的 NPY mRNA 表达上调及 POMC mRNA 表达下调。结论 肾衰养真胶囊可改善 CRF 营养不良大鼠的营养状况,其机制可能是通过上调下丘脑 NPY mRNA 表达,下调下丘脑 POMC mRNA 表达,从而促进大鼠摄食。     

Oxytocin inhibits the stimulatory effect of ghrelin on circulating neuropeptide Y levels in humans

Oxytocin (OT) effect on ghrelin-stimulated neuropeptide Y (NPY) secretion was evaluated in 12 normal men. Tests: ghrelin (1 mug/kg B.W. as an intravenous bolus); OT (2 mIU/min infusion); ghrelin plus OT; normal saline. Plasma NPY did not change during saline or OT infusions, whereas it showed a significant 29% increase vs baseline at 15 min after ghrelin injection. When OT was present, ghrelin-induced NPY increment was completely abolished. Results show that oxytocin modulates the NPY response to ghrelin, whereas it is unable to produce direct inhibitions of basal circulating NPY levels.     

Acute stress differentially affects corticotropin-releasing hormone mRNA expression in the central amygdala of the "depressed" flinders sensitive line and the control flinders resistant line rats

Preclinical and clinical evidence suggests that neuropeptides play a role in the pathophysiology of mood disorders. In the present study, we investigated the involvement of the peptides corticotropin-releasing hormone (CRH), neuropeptide Y (NPY) and nociceptin/orphanin FQ (N/OFQ) and of their receptors in the regulation of emotional behaviours. In situ hybridization experiments were performed in order to evaluate the mRNA expression levels of these neuropeptidergic systems in limbic and limbic-related brain regions of the Flinders Sensitive Line (FSL) rats, a putative genetic animal model of depression. The FSL and their controls, the Flinders Resistant Line (FRL) rats, were subjected to one hour acute restraint and the effects of the stress exposure, including possible strain specific changes on these neuropeptidergic systems, were studied. In basal conditions, no significant differences between FSL and FRL rats in the CRH mRNA expression were found, however an upregulation of the CRH mRNA hybridization signal was detected in the central amygdala of the stressed FRL, compared to the non stressed FRL rats, but not in the FSL, suggesting a hypoactive mechanism of response to stressful stimuli in the "depressed" FSL rats. Baseline levels of NPY and N/OFQ mRNA were lower in the FSL rats compared to the FRL in the dentate gyrus of hippocampus and in the medial amygdala, respectively. However, the exposure to stress induced a significant upregulation of the N/OFQ mRNA levels in the paraventricular thalamic nucleus, while in the same nucleus the N/OFQ receptor mRNA expression was higher in the FSL rats. In conclusion, selective alterations of the NPY and N/OFQ mRNA in limbic and limbic-related regions of the FSL rats, a putative animal model of depression, provide further support for the involvement of these neuropeptides in depressive disorders. Moreover, the lack of CRH activation following stress in the "depressed" FSL rats suggests a form of allostatic load, that could alter their interpretation of environmental stimuli and influence their behavioural response to stressful situations.     

扇贝多肽对化疗后食欲减退模型大鼠食欲及NPY表达的影响

目的研究扇贝多肽（PCF）对化疗后食欲减退大鼠食欲刺激因子神经肽Y（NPY）表达的影响。方法将36只大鼠随机分为3组,即空白组、模型组、PCF组,每组12只。PCF组用PCF对化疗后食欲减退模型大鼠进行灌喂,观察其进食量、体重的变化,并应用放射免疫检测法测定其下丘脑和血浆NPY的含量,比较其与空白组、模型组的差异。结果试验后空白组进食量、体重与模型组有显著差异（P〈0.01）;PCF组与空白组进食量、体重也有显著差异（均P〈0.01）。试验后空白组与模型组下丘脑NPY含量有显著差异（P〉0.05）,PCF组与空白组下丘脑NPY含量有显著差异（P〈0.05）;试验后空白组与模型组血清NPY含量有显著差异（P〈0.05）,PCF组与空白组血清NPY含量有显著差异（P〈0.05）;试验后空白组与模型组脑血NPY之比有显著差异（P〈0.05）,PCF组与空白组脑血NPY之比有显著差异（P〈0.05）。体重与下丘脑NPY含量相关系数为0.704,P=0.0026;体重与血浆NPY含量相关系数为0.628,P=0.0037,均P〈0.05。结论 PCF可显著增加化疗后大鼠的进食量与体重,其机理与PCF能增加化疗后食欲减退大鼠外周血和中枢神经肽Y的含量有关。     

穴位埋线及中药对去势肥胖大鼠瘦素与下丘脑-垂体-性腺轴的影响

目的:探讨穴位埋线与中药加味对去势肥胖大鼠瘦素(LP)、神经肽Y(NPY)及下丘脑-垂体-卵巢轴(H-P-O)的调节作用。方法:选用双侧卵巢切除法复制去势肥胖模型,分组治疗后观察去势肥胖大鼠体质量、Lee,s指数、腹腔脂肪湿重、血清雌二醇E2、促卵泡生成素(FSH)、LP、NPY,下丘脑促性腺激素释放素(GnRH)、下丘脑弓状核瘦素受体(OB-R)阳性细胞数及脂肪细胞计数的变化。结果:各治疗组治疗后大鼠肥胖指标不同程度下降。LP、NPY、GnRH、FSH水平下降,E2水平上升,下丘脑弓状核瘦素受体(OB-R)阳性细胞数增加。结论:经过穴位埋线加中药治疗,可改善H-P-O轴平衡失调和瘦素抵抗,达到减肥效果。     

氯沙坦对高血压血浆神经肽Y含量的干预研究

目的 观察应用氯沙坦前后高血压患者血浆神经肽Y(NPY)含量的变化,探讨血管紧张素Ⅱ(AⅡ)受体拮抗剂与NPY的相关性。方法 采用放免法测定40例高血压患者应用氯沙坦前后血浆NPY的含量及AⅡ水平,同期测定另外40例高血压患者应用美托洛尔前后血浆NPY的含量及AⅡ水平。结果40例高血压患者应用氯沙坦前后血浆NPY水平分别为(152.4±12.3)pg/ml、(125.5±9.5)pg/ml,P<0.01;血浆AⅡ水平分别为(49.6±7.1)pg/ml、(62.4±7.8)pg/ml,P<0.01。40例高血压患者应用美托洛尔前后血浆NPY水平分别为(144.1±11.3)pg/ml、(140.6±12.2)pg/ml,P>0.05;血浆AⅡ水平分别为(45.5±5.8)pg/ml、(48.3±7.2)pg/ml,P>0.05。治疗后2组之间比较,NPY、AⅡ水平均有非常显著性差异(P<0.01)。结论 氯沙坦能影响血浆NPY水平,提示该药降压的过程中有NPY参与的因素,而美托洛尔却不影响血浆NPY水平。     

The role of selected neuropeptides in pathogenesis of atopic dermatitis

Background Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD. Objective The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease. Material and methods Forty‐nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay. Results Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation.