Direct inhibition of arcuate kisspeptin neurones by neuropeptide Y in the male and female mouse

Adverse energy states exert a potent suppressive influence on the reproductive axis by inhibiting the pulsatile release of gonadotrophin‐releasing hormone and luteinising hormone. One potential mechanism underlying this involves the metabolic‐sensing pro‐opiomelanocortin and agouti‐related peptide/neuropeptide Y (AgRP/NPY) neuronal populations directly controlling the activity of the arcuate nucleus kisspeptin neurones comprising the gonadotrophin‐releasing hormone pulse generator. Using acute brain slice electrophysiology and calcium imaging approaches in Kiss1‐GFP and Kiss1‐GCaMP6 mice, we investigated whether NPY and α‐melanocyte‐stimulating hormone provide a direct modulatory influence on the activity of arcuate kisspeptin neurones in the adult mouse. NPY was found to exert a potent suppressive influence upon the neurokinin B‐evoked firing of approximately one‐half of arcuate kisspeptin neurones in both sexes. This effect was blocked partially by the NPY1R antagonist BIBO 3304, whereas the NPY5R antagonist L152,804 was ineffective. NPY also suppressed the neurokinin B‐evoked increase in intracellular calcium levels in the presence of tetrodotoxin and amino acid receptor antagonists, indicating that the inhibitory effects of NPY are direct on kisspeptin neurones. By contrast, no effects of α‐melanocyte‐stimulating hormone were found on the excitability of arcuate kisspeptin neurones. These studies provide further evidence supporting the hypothesis that AgRP/NPY neurones link energy status and luteinising hormone pulsatility by demonstrating that NPY has a direct suppressive influence upon the activity of a subpopulation of arcuate kisspeptin neurones.     

Inhibitory neuronal changes following a mixed diffuse-focal model of traumatic brain injury

Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range of chronic neurological deficits. However, how TBI affects different interneurons, and how this relates to behavioral abnormalities, remains poorly understood. This study examined the effects of a mixed diffuse-focal model of TBI, the lateral fluid percussion injury (LFPI), on interneurons, 8 weeks post-TBI in rats. Brains were labeled with antibodies against calbindin, parvalbumin, calretinin, neuropeptide Y, and somatostatin, and the number of interneurons were assessed in the cortex and hippocampus following LFPI. LFPI caused a reduction in the numbers of interneurons mediating both perisomatic and dendritic inhibition in the somatosensory cortex. In hippocampus, there were heterogenous changes in the number of interneurons while motor cortex, showed no obvious loss in any of the subsets of interneurons after TBI. In parallel to the investigations of changes in the number of interneurons, we also investigated the long-term behavioral consequences of LFPI. Behaviorally, rats given an LFPI displayed transient reduction in performance in motor tasks and were significantly impaired in reversal learning in the water maze task post-TBI. We also report here progressive neurodegeneration in cortex and hippocampus indicated by Fluoro-Jade C in the different brain areas examined after injury. Our findings suggest differential vulnerability of inhibitory neurons to LFPI in the different brain areas examined after injury. These data will aid in evaluation of new treatments for TBI and help target specific neuronal subtypes as a function of injury time and type.     

Neuropeptide Y modulates membrane excitability in neonatal rat mesencephalic V neurons

Neuropeptide Y (NPY) is one of a number of neuropeptides with powerful orexigenic effects. Intracerebroventricular administration of NPY induces increases in food intake and alters feeding rate. Besides it role in feeding behavior, NPY also has significant effects on neuronal systems related to other spontaneous behaviors such as rearing and grooming. In the present study, we examined the direct effects of NPY on mesencephalic V neurons (Mes V), which are important sensory neurons involved in oral motor reflexes and rhythmical jaw movements, as well as masticatory proprioception. Coronal brain slices were prepared from neonatal Sprague-Dawley rats (P3-17) and whole-cell patch clamp recordings were obtained from Mes V neurons. Bath application of NPY depolarized the membrane potential and induced inward current in most neurons. Application of NPY shortened the duration of the afterhyperpolarization following an action potential, and increased the mean spike frequency during repetitive discharge. In those neurons which exhibited rhythmical burst discharge in response to maintained current injection, the bursting frequency was also increased. These effects were mediated predominately by both Y1 and Y5 receptors.     

鼠颞下颌关节创伤后感觉神经肽阳性纤维的变化

目的:观察间接创伤后鼠颞下颌关节中感觉神经肽阳性纤维分布及密度的动态变化,探讨感觉神经肽在颞下颌关节疾病中的作用。方法:将42只SD大鼠随机均分为6组,分别在创伤前、创伤后1、3、7、14和28d时处死,灌注同定后取双侧颞下颌关节,脱钙后恒冷切片,ABC法漂染,并对结果进行半定量分析。结果:创伤前鼠颞下颌关节中有广泛而丰富的降钙素基因相关肽和P物质阳性纤维的分布。创伤后两种神经肽阳性纤维的密度均显著降低,分别在创伤后3、1d达到最低值。然后逐渐增加,至28d时达到或超过正常值。结论:创伤后颞下颌关节中感觉神经肽的逆行释放显著增加。它们不仅参与痛觉传导,而且是颞下颌关节病理改变的神经源因素。     

下牙槽神经相关神经肽及其非神经传导功能

下牙槽神经作为一种混合神经,不仅可以通过外感受器发挥神经传导功能,而且还可通过释放神经肽发挥其非神经传导功能。神经肽是一类由神经细胞合成并释放,通过细胞外的受体对目标细胞发挥调节作用的生物活性多肽,与下牙槽神经相关的神经肽主要有P物质、降钙素基因相关肽、神经肽Y和神经激肽A等。下牙槽神经可以通过释放这些神经肽调节牙体发育及神经源性炎症,维持体内免疫稳态、促进骨折愈合,在组织的修复再生中起重要作用。通过对下牙槽神经非传导作用的研究,进一步从分子、细胞及组织多层面探讨神经与组织再生间的关系,揭示神经因素在促进组织再生并提高其再生质量等方面的作用,将成为未来重要的研究方向。本文将就下牙槽神经及其非神经传导作用作一综述。     

Effects of SR 48968 on the neuropeptide gamma-induced contraction of the human isolated bronchus

Summary— Neuropeptide gamma (NPγ) induced a contractile response of the human isolated bronchus which was potentiated by the neutral endopeptidase inhibitor, phosphoramidon, but was not modified by atropine and indomethacin. NPγ was 3.31-fold more potent than NKA. Contractile response curves to NPγ were shifted to the right and maximal responses reduced by the non-peptide NK₂-receptor antagonist, SR 48968. The pK_B of SR 48968 (8.94 ± 0.18, n = 15), calculated according to Kenakin (1987) was very close to that reported for [Nle¹⁰]-NKA (4–10), a specific agonist of neurokinin NK₂-receptors (8.86 ± 0.13, n = 13), suggesting that the contractile effects of NPγ on the human isolated bronchus were mediated through NK_2A-receptors.     

氯氮平、阿立哌唑对精神分裂症患者血浆神经肽Y、瘦素水平的影响及其与体质量变化的关系

目的:探讨氯氮平和阿立哌唑对精神分裂症患者血浆神经肽Y、瘦素水平的影响及其与体质量变化的关系。方法:60例精神分裂症患者随机分为氯氮平组和阿立哌唑组各30例,分别接受氯氮平和阿立哌唑治疗6周。于治疗前及治疗3周和6周后分别测定两组血浆神经肽Y、瘦素水平及体质量,并进行治疗前后的比较及回归分析。结果:重复测量方差分析显示,血浆神经肽Y、瘦素水平及体质量存在交互效应(F=11.203,P=0.000;F=5.981,P=0.033;F=7.523,P=0.003)和组别主效应(F=6.772,P=0.023;F=37.771,P=0.000;F=5.674,P=0.039)。治疗3周和6周时,氯氮平组血浆神经肽Y水平(F=30.764,P=0.000;F=59.963,P=0.000)、体质量(F=5.424,P=0.042;F=11.423,P=0.000)均高于治疗前;治疗6周时,血浆瘦素水平显著高于治疗前(F=10.132,P=0.004)。阿立哌唑组血浆神经肽Y(F=0.143,P=0.708;F=0.293,P=0.593)、瘦素水平(F=1.343,P=0.256;F=1.030,P=0.326)、体质量(F=2.743,P=0.113;F=0.132,P=0.722)与治疗前比较差异无统计学意义。逐步回归分析显示,治疗3周和6周时神经肽Y变化值可以解释同期体质量变化值变异的41.9%和21.8%。结论:与阿立哌唑比较,氯氮平可显著增加精神分裂症患者血浆神经肽Y、瘦素水平;神经肽Y水平增高可能是氯氮平导致患者体质量增加的内因之一。