Neuropeptides and the central regulation of body temperature during fever and hibernation

Neuropeptides, acting on structures within the central nervous system influence body temperature. Non-opioid peptides induce hypothermia usually, while opioid peptides are mostly hyperthermic. Neuropeptides exert their effect only when injected into specific brain areas.

Hypo- Or hyperthermic effect of neuropeptides may be either due to changes in threshold body temperatures for induction of thermoregulatory effectors or due to changes in hypothalamic thermosensitivity.

At the cellular level the opioid peptides also act differently than the non-opioid peptides. The opioid peptides mostly inhibit spontaneous neuronal firing, while the non-opioid peptides usually stimulate it. Neuropeptides exert their influence on all neurones in the hypothalamus, independently on their temperature characteristics.

Neuropeptides may play a role in the regulation of body temperature under stressful conditions and during fever or hibernation, in particular. Some neuropeptides, namely AVP, -MSH and ACTH, act as natural antipyretic substances by lowering the threshold for cold thermogenesis.

Neuropeptides also modulate food intake, reproduction and many other functions which are substantially changed during hibernation. There appears to be a correlation between the effect of peptides on the control of food intake and on the control of body temperature. Opioid peptides, which increase food intake, induce hyperthermia, while non-opioid peptides, which are appetite inhibiting, induce hypothermia. The exact role o neuropeptides in the regulation of body temperature, food intake and gonadal activity of hibernators remains unclear, however.     

Hydra Peptide Project 1993–2007

A systematic screening of peptide signaling molecules (<5000 da) in Hydra magnipapillata (the Hydra Peptide Project) was launched in 1993 and at least the first phase of the project ended in 2007. From the project a number of interesting suggestions and results have been obtained. First, a simple metazoan-like Hydra appears to contain a few hundred peptide signaling molecules: half of them neuropeptides and the rest epitheliopeptides that are produced by epithelial cells. Second, epitheliopeptides were identified for the first time in Hydra . Some exhibit morphogen-like activities, which accord with the notion that epithelial cells are primarily responsible for patterning in Hydra . A family of epitheliopeptides was involved in regulating neuron differentiation possibly through neuron–epithelial cell interaction. Third, many novel neuropeptides were identified. Most of them act directly on muscle cells inducing contraction or relaxation. Some were involved in cell differentiation and morphogenesis. During the course of this study, a number of important technical innovations (e.g. genetic manipulations in transgenic Hydra , high-throughput purification techniques, etc.) and expressed sequence tag (EST) and genome databases were introduced in Hydra research. They have already helped to identify and characterize novel peptides and will contribute even more to the Hydra Peptide Project in the near future.     

The neuroactive substances and associated muscle system in Rhipidocotyle campanula (Digenea,Bucephalidae) from the intestine of the pike Esox lucius

We report about the muscular system and the serotonergic and FMRFamidergic components of the nervous system of the Bucephalidae trematode, Rhipidocotyle campanula, an intestinal parasite of the pike. We use immunocytochemical methods and confocal scanning laser microscopy (CLSM). The musculature is identified by histochemical staining with fluorescently labeled phalloidin. The body wall musculature of R. campanula contains three layers of muscle fibres – the outer thin circular, intermediate longitudinal and inner diagonal muscle fibres running in two opposite directions. The digestive system of R. campanula possess of a well-developed musculature: radial, longitudinal and circular muscle elements are detected in the pharynx, circular and longitudinal muscle filaments seen in the oesophagus, and longitudinal and the circular muscle fibres were found in the intestinal wall. Specific staining indicating the presence of actin muscle filaments occurs in the cirrus sac localized in the posterior body region. The frontal region of anterior attachment organ, the rhynchus, in R. campanula is represented by radial muscle fibres. The posterior part of the rhynchus comprise of radial muscles forming the organ's wall, and several strong longitudinal muscle bundles. Serotonergic and FMRFamidergic structures are detected in the central and peripheral compartments of the nervous system of R. campanula, that is, in the paired brain ganglia, the brain commissure, the longitudinal nerve cords, and connective nerve commissures. The innervations of the rhynchus, pharynx, oesophagus and distal regions of the reproductive system by the serotonergic and FMRFamidergic nervous elements are revealed. We compare our findings obtained on R. campanula with related data for other trematodes.     

Role of neurotransmitters and neuropeptides in the control of gonadotropin release: A review

Rapid progress has been recorded recently in the understanding of the role of neuro-transmitters and neuropeptides in the control of reproduction and on their apparent potential in the regulation of fertility. Peptides, as well as monoamines, are important in the control of lutinizing hormone releasing hormone and gonadotropin release. The input from brainstem noradrenergic neurons as well as dopamine mediated stimulated release of lutinizing hormone. In addition considerable evidence exist for the occurrence of a specific follicle stimulating hormone-releasing factor. A large number of brain peptides affect the secretion of lutinizing hormone releasing hormone and the endogenous opioid peptides appear to have a physiologically important function in restraining the influence on lutinizing hormone releasing hormone release under most circumstances. Vasoactive intestinal peptide and substanceP stimulate whereas cholecystokinin, neurotensin, gastrin, secretin, somatostatin α-melanosite stimulating hormone and vasotocin inhibit lutinizing hormone release. Of the inhibitory peptides, cholecystokinin and arg-vasotocin are the most potent. Inhibin injected into the ventricle selectively suppresses follicle stimulating hormone release by a hypothalamic action. Thus the control of gonadotropin release is complex and a number of aminergic and peptidergic transmitters are involved.     

Identification of two novel genes specifically expressed in the D-group neurons of the terrestrial snail CNS

A search for genes specifically expressed in the giant interneurons of parietal ganglia of the snailHelix lucorum yielded, among others, two genes named HDS1 and HDS2. According to data obtained by Northern hybridization and whole-mountin situ hybridization, both genes are neurospecific and expressed almost exclusively in the peptidergic D-group neurons (Sakharov, 1974) located in the right parietal ganglion.In situ hybridization of the HDS1 and HDS2 probes with CNS of several related species of the Helicoidea superfamily identified in all cases similarly located homologous groups of neurons. Sequencing of the near full-length cDNA copies of the HDS1 and HDS2 genes revealed open reading frames 107 and 102 amino acids long for HDS1 and HDS2, respectively. Both putative proteins contain a hydrophobic leader peptide and putative recognition sites for furin-like and PC-like endopeptidases. Predicted amino acid sequences of the HDS1 and HDS2 proteins were found to be moderately homologous to each other, as well as to the LYCP preprohormone expressed by the light yellow cells of the freshwater snailLymnaea stagnalis. These results confirm an earlier hypothesis that the D-group of theHelix family and the light yellow cells ofLymnaea stagnalis represent homologous neuronal groups. Our data suggest that the HDS1 and HDS2 genes encode precursors of secreted molecules, most likely neuropeptides or neurohormones.     

A phylogenetic analysis of the adipokinetic neuropeptides of Ensifera

Abstract.  Adipokinetic neuropeptides, from the corpora cardiaca of various species of the suborder Ensifera, encompassing members of all superfamilies (except the Gryllacridoidea), were isolated by liquid chromatography, and identified structurally by comparison of retention times and mass spectrometry data with respect to information from known members of this peptide family. Ensiferan species always contain only one adipokinetic hormone (AKH) peptide, as assessed for a few species by monitoring typical AKH mass peaks from a crude corpora cardiaca extract. This AKH is an octapeptide, and is either Scg-AKH-II (pGlu-Leu-Asn-Phe-Ser-Thr-Gly-Trp amide) which occurs in all Tettigoniidea (except Schizodactyloidea) and in Gryllotalpoidea, or Grb-AKH (pGlu-Val-Asn-Phe-Ser-Thr-Gly-Trp amide) which occurs in Grylloidea (except Gryllotalpoidea) and Schizodactyloidea. Using the structural information of these neuropeptides in conjunction with morpho-anatomical characters, these data are interpreted in a phylogenetic framework. The lack of a decapeptide and the presence of the octapeptide Scg-AKH-II are ancestral in Ensifera. The ancestral Scg-AKH-II twice underwent an independent and convergent modification to Grb-AKH.     

D-Amino Acids in Living Higher Organisms

The homochirality of biological amino acids (L-amino acids) andof the RNA/DNA backbone (D-ribose) might have become establishedbefore the origin of life. It has been considered that D-aminoacids and L-sugars were eliminated on the primitive Earth.Therefore, the presence and function of D-amino acids in livingorganisms have not been studied except for D-amino acids in thecell walls of microorganisms. However, D-amino acids wererecently found in various living higher organisms in the form offree amino acids, peptides, and proteins. Free D-aspartate andD-serine are present and may have important physiologicalfunctions in mammals. D-amino acids in peptides are well knownas opioid peptides and neuropeptides. In protein, D-aspartateresidues increase during aging. This review deals with recentadvances in the study of D-amino acids in higher organisms.     

强噪声对豚鼠认知功能和血清某些生化指标的影响

目的：探讨强噪声对豚鼠认知功能和血清应激激素、代谢酶、神经肽、脑红蛋白等的影响,筛选噪声性认知功能损伤的敏感指标。方法：将24只豚鼠进行5 d的认知功能训练,第6天随机分为2组（n=12）：噪声组和对照组。噪声组在120 dB噪声下连续暴露4h后,用Morris水迷宫测试豚鼠的认知能力;用Elisa试剂盒检测豚鼠血清神经肽Y（NPY）、神经肽P（NPP）、脑红蛋白（NGB）、C反应蛋白（CRP）、皮质醇（CORT）、促肾上腺皮质激素（ACTH）、促肾上腺皮质激素释放激素（CRH）、肾上腺素（E）、去甲肾上腺素（NE）、血管紧张素Ⅱ（AngⅡ）、醛固酮（ALD）、催产素（OT）、血管升压素（VAP）含量、谷草转氨酶（ALT）、谷丙转氨酶（AST）、乳酸脱氢酶（LDH）、肌酸激酶（CK）的活性;用回归分析评价各项敏感指标对认知功能的影响及程度。结果：Morris水迷宫测试显示,与对照组相比,噪声组豚鼠的平均逃避潜伏期明显延长,跨越平台次数和目标象限停留时间均明显降低（P<0.01）。Elisa检测发现,除AngⅡ外,噪声组豚鼠血清中上述指标均与对照组有明显的统计学差异（P<0.05,P<0.01）,其中变化显著且对认知功能影响较大的指标依次为CORT、NPY、NE、NGB、NPP、CK。结论：强噪声急性暴露引起豚鼠认知功能显著下降,可能与外周血应激激素、代谢酶、神经肽、脑红蛋白等生化指标的异常有关,并初步筛选出了CORT、NPY、NE、NGB、NPP、CK等与噪声性认知功能损伤有关的敏感指标群。     

Neuropeptides and photic behavior in Cnidaria

Peptides of the RFamide family occur in neurosecretory cells of all nervous systems of Cnidaria so far studied. Photoreceptive organs – if evolved in a cnidarian species – are always associated with neural cells showing RFamide immunoreactivity. Experimental evidence for the function of RFamides and other neuropeptides in nervous systems and photoreceptive organs is, however, scarce or lacking. RFamide and LWamide immunoreactivity were surveyed in photoreceptive organs of the hydromedusa Cladonema radiatum, in rhopalia of the scyphozoan Aurelia aurita, and in rhopalia of the cubomedusa Tripedalia cystophora. A possible function of neuropeptides in transmission of photic stimuli was assayed by analysing photic behavior in Tripedalia, which has highly developed eyes, and in the simply constructed planula of the hydroid Hydractinia echinata, in which the mode of light perception is unknown. In both species, light orientation was effectively prevented by RFamides administered to the animals in micromolar concentration. In contrast, among four other neuropeptides occurring in the larva of Hydractinia, only one interfered with phototaxis and then only at 10× higher concentrations. Planulae depleted of bioactive peptideamides also lost phototaxis while still locomotorily active. The results support the hypothesis that one possible function of RFamides in Cnidaria is to transmit photic stimuli to epitheliomuscular targets.     

Regulation of the pharynx of Caenorhabditis elegans by 5‐HT,octopamine, and FMRFamide‐like neuropeptides

More than fifty FMRFamide‐like neuropeptides have been identified in nematodes. We addressed the role of a subset of these in the control of nematode feeding by electrophysiological recording of the activity of C. elegans pharynx. AF1 (KNEFIRFamide), AF2 (KHEYLRFamide), AF8 (KSAYMRFamide), and GAKFIRFamide (encoded by the C. elegans genes flp‐8, flp‐14, flp‐6, and flp‐5, respectively) increased pharyngeal action potential frequency, in a manner similar to 5‐HT. In contrast, SDPNFLRFamide, SADPNFLRFamide, SAEPFGTMRFamide, KPSVRFamide, APEASPFIRFamide, and AQTVRFamide (encoded by the C. elegans genes flp‐1; flp‐1; flp‐3; flp‐9; flp‐13, and flp‐16, respectively) inhibited the pharynx in a manner similar to octopamine. Only three of the neuropeptides had potent effects at low nanomolar concentrations, consistent with a physiological role in pharyngeal regulation. Therefore, we assessed whether these three peptides mediated their actions either directly on the pharynx or indirectly via the neural circuit controlling its activity by comparing actions between wild‐type and mutants with deficits in synaptic signaling. Our data support the conclusion that AF1 and SAEPFGTMRFamide regulate the activity of the pharynx indirectly, whereas APEASPFIRFamide exerts its action directly. These results are in agreement with the expression pattern for the genes encoding the neuropeptides (Kim and Li, 1999) as both flp‐8 and flp‐3 are expressed in extrapharyngeal neurons, whereas flp‐13 is expressed in I5, a neuron with synaptic output to the pharyngeal muscle. These results provide the first, direct, functional information on the action of neuropeptides in C. elegans. Furthermore, we provide evidence for a putative inhibitory peptidergic synapse, which is likely to have a role in the control of feeding. © 2001 John Wiley & Sons, Inc. J Neurobiol 49: 235–244, 2001