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1.
Results Probl Cell Differ ; 68: 107-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598854

RESUMO

The critical phylogenetic position of the ascidian, Ciona intestinalis, as the closest relative of vertebrates, suggested its potential applicability as a model organism in a wide variety of biological events including the nervous, neuroendocrine, and endocrine regulation. To date, approximately 40 neuropeptides and/or peptide hormones and several cognate receptors have been identified. These peptides are categorized into two types: (1) orthologs of vertebrate peptides, such as cholecystokinin, GnRH, tachykinin, vasopressin, and calcitonin, and (2) novel family peptides such as LF peptides and YFL/V peptides. Ciona GnRH receptors (Ci-GnRHR) were found to be multiplicated in the Ciona-specific lineages and to form unique heterodimers between Ci-GnRHR1 and R4 and between Ci-GnRHR2 and R4, leading to fine-tuning of the generation of second messengers. Furthermore, Ciona tachykinin was shown to regulate a novel protease-associated follicle growth pathway. These findings will pave the way for the exploration of both conserved and diversified endocrine, neuroendocrine, and nervous systems in the evolutionary lineage of invertebrate deuterostomes and/or chordates. In this chapter, we provide an overview of primary sequences, functions, and evolutionary aspects of neuropeptides, peptide hormones, and their receptors in C. intestinalis.


Assuntos
Ciona intestinalis/metabolismo , Neuropeptídeos/metabolismo , Hormônios Peptídicos/metabolismo , Receptores de Peptídeos/metabolismo , Animais , Filogenia
2.
Arch Insect Biochem Physiol ; 102(1): e21598, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290186

RESUMO

At present, the effect of ultraviolet (UV) radiation on the interaction between Bombyx mori nucleopolyhedrovirus (BmNPV) and host remains unclear. In the current study, UV treatment significantly reduced the activity of BmNPV budded viruses (BVs), and UV-damaged BmN cells were not conducive to BmNPV proliferation. BmNPV infection significantly reduced the viability of host cells, but increased the viability of high-dose UV-treated host cells. Furthermore, the quantitative reverse-transcription PCR (qPCR) results suggested that BmNPV and Bombyx mori might mutually use the same DNA repair proteins for repairing UV-induced damage and BmNPV infection promote the ability of host cells to repair UV-induced damage.


Assuntos
Bombyx/virologia , Interações Hospedeiro-Patógeno/efeitos da radiação , Nucleopolyhedrovirus/efeitos da radiação , Animais , Bombyx/imunologia , Bombyx/metabolismo , Bombyx/efeitos da radiação , Sobrevivência Celular , Células Cultivadas , Endonucleases Flap/metabolismo , Neuropeptídeos/metabolismo , Raios Ultravioleta
3.
Nat Commun ; 10(1): 3097, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308381

RESUMO

Dopaminergic neurons in the brain of the Drosophila larva play a key role in mediating reward information to the mushroom bodies during appetitive olfactory learning and memory. Using optogenetic activation of Kenyon cells we provide evidence that recurrent signaling exists between Kenyon cells and dopaminergic neurons of the primary protocerebral anterior (pPAM) cluster. Optogenetic activation of Kenyon cells paired with odor stimulation is sufficient to induce appetitive memory. Simultaneous impairment of the dopaminergic pPAM neurons abolishes appetitive memory expression. Thus, we argue that dopaminergic pPAM neurons mediate reward information to the Kenyon cells, and in turn receive feedback from Kenyon cells. We further show that this feedback signaling is dependent on short neuropeptide F, but not on acetylcholine known to be important for odor-shock memories in adult flies. Our data suggest that recurrent signaling routes within the larval mushroom body circuitry may represent a mechanism subserving memory stabilization.


Assuntos
Encéfalo/fisiologia , Neurônios Dopaminérgicos/fisiologia , Drosophila melanogaster/fisiologia , Memória/fisiologia , Corpos Pedunculados/fisiologia , Recompensa , Acetilcolina/metabolismo , Animais , Apetite/fisiologia , Encéfalo/citologia , Condicionamento Clássico , Retroalimentação Fisiológica , Larva , Modelos Psicológicos , Corpos Pedunculados/citologia , Vias Neurais/fisiologia , Neuropeptídeos/metabolismo , Odorantes , Percepção Olfatória/fisiologia , Optogenética
4.
Arch Insect Biochem Physiol ; 101(4): e21587, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31271487

RESUMO

The codling moth, Cydia pomonella, is a worldwide pest of pome fruits. Neuropeptides regulate most physiological functions in insects and represent new targets for the development of control agents. The only neuropeptides reported from the codling moth to date are the allatostatin A family peptides. To identify other neuropeptides and peptide hormones from codling moth, we analyzed head transcriptomes, identified 50 transcripts, and predicted 120 prepropeptides for the codling moth neuropeptides and peptide hormones. All transcripts were amplified, and these sequences were verified. One of the notable findings in this study is that diapause hormones (DHs) reported from Tortricid moths, including the codling moth, do not have the WFGPRL sequence in C-terminal ends in the pban genes. The C-terminal motif is critical to characterize insect DH peptides, and always conserved in pban/dh genes in Lepidoptera and many insect orders. Interestingly, the WFGPRL sequence was produced only from the capa gene in the codling moth. The allatostatin A-family encoding transcript predicted nine peptides, seven of which, as expected, are identical to those previously isolated from the moth. We also identified new codling moth orthologs of insect neuropeptides including CCHamides, allatostatin CC, RYamides, and natalisins. The information provided in this study will benefit future codling moth investigations using peptidoproteomics to determine peptide presence and functions.


Assuntos
Mariposas/metabolismo , Neuropeptídeos/metabolismo , Hormônios Peptídicos/metabolismo , Sequência de Aminoácidos , Animais , Clonagem Molecular , Regulação da Expressão Gênica , Neuropeptídeos/química , Hormônios Peptídicos/química
5.
BMC Complement Altern Med ; 19(1): 147, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234859

RESUMO

BACKGROUND: Ethanol withdrawal (EtOHW) anxiety is a crucial risk factor for alcoholic relapse. The neuropeptide nociceptin/orphanin FQ (N/OFQ) acts upon its receptor (NOP) to antagonize corticotropin-releasing factor (CRF) and elicit anxiolytic actions. Semen Ziziphi Spinosae (SZS), a prototypical hypnotic-sedative herb in Oriental medicine, exhibits anxiolytic effects during nicotine withdrawal by improving amygdaloid CRF/CRF1 receptor (CRFR1) signaling. Therefore, we evaluated the effects of SZS on EtOHW anxiety and the involvement of amygdaloid CRF/CRFR1 and N/OFQ/NOP pathways. METHODS: Male Sprague Dawley rats received intraperitoneal injections of 2 g/kg EtOH (20% v/v) once daily for 28 d followed by a 3-d withdrawal. During EtOHW, the rats were given once-daily intragastric treatments of a methanol extract of SZS (MESZS, 60 or 180 mg/kg/d). Anxiety-like behaviors were measured with the open field (OF) and elevated plus maze (EPM) tests, and plasma corticosterone (CORT) levels were examined by an enzyme-linked immunosorbent assay. mRNA and protein expression levels of the neuropeptides and their receptors were determined by quantitative polymerase chain reaction and Western blot assays. RESULTS: MESZS increased the distance traveled in the center zone of the OF and dose-dependently elongated the duration of staying in the center zone in EtOHW rats. MESZS increased both the number of entries into and the time spent in the open arms of the EPM by EtOHW rats. And, MESZS inhibited the over secretion of plasma CORT during EtOHW. EtOHW enhanced CRF and CRFR1 gene and protein expression in the central nucleus of the amygdala (CeA), which were inhibited by 180 mg/kg/d MESZS. EtOHW increased amygdaloid NOP mRNA and protein expression but spared N/OFQ mRNA expression, and 180 mg/kg/d MESZS further promoted these increases. Additionally, a post-MESZS intra-CeA infusion of either CRF or the selective NOP antagonist UFP-101 abolished the expected anxiolytic effect of 180 mg/kg/d MESZS. CONCLUSIONS: These results suggest that MESZS ameliorates EtOHW anxiety by improving both CRF/CRFR1 and N/OFQ/NOP transmissions in the CeA.


Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Núcleo Central da Amígdala/efeitos dos fármacos , Etanol/efeitos adversos , Neuropeptídeos/metabolismo , Síndrome de Abstinência a Substâncias/complicações , Ziziphus/química , Animais , Ansiedade/etiologia , Ansiedade/genética , Ansiedade/metabolismo , Núcleo Central da Amígdala/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Sementes/química
6.
Biochim Biophys Acta Rev Cancer ; 1872(1): 66-73, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152820

RESUMO

Increasing studies have demonstrated that neuroendocrine system is involved in the development and progression of cholangiocarcinoma. The neuroendocrine hormones, neurotransmitters and neuropeptides regulate cholangiocarcinoma via affecting pathophysiology of tumor cells. The developing interaction and interplay between neuroendocrine-associated factors and tumor cells provide novel insights into neural control of tumorigenesis and reveal potential therapeutic effect on patients with cholangiocarcinoma. Herein we reviewed the latest findings and achievements which demonstrate the close interactions between neuroendocrine regulation and progression of cholangiocarcinoma. Also, future therapeutic approaches targeting neuroendocrine-associated factors are discussed which may help improve management and treatment of cholangiocarcinoma.


Assuntos
Colangiocarcinoma/genética , Neoplasias Hepáticas/genética , Sistemas Neurossecretores/metabolismo , Colangiocarcinoma/patologia , Humanos , Neoplasias Hepáticas/patologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Sistemas Neurossecretores/patologia , Neurotransmissores/genética , Neurotransmissores/metabolismo
7.
Mol Cells ; 42(4): 301-312, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31091556

RESUMO

Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24 h rhythms of free-running locomotor activity. RNA interference-mediated depletion of key NMD factors in timeless-expressing clock cells decreased the amplitude of circadian locomotor behaviors. Transgenic manipulation of the NMD pathway in clock neurons expressing a neuropeptide PIGMENT-DISPERSING FACTOR (PDF) was sufficient to dampen or lengthen free-running locomotor rhythms. Confocal imaging of a transgenic NMD reporter revealed that arrhythmic Clock mutants exhibited stronger NMD activity in PDF-expressing neurons than wild-type. We further found that hypomorphic mutations in Suppressor with morphogenetic effect on genitalia 5 (Smg5 ) or Smg6 impaired circadian behaviors. These NMD mutants normally developed PDF-expressing clock neurons and displayed daily oscillations in the transcript levels of core clock genes. By contrast, the loss of Smg5 or Smg6 function affected the relative transcript levels of cAMP response element-binding protein B (CrebB ) in an isoform-specific manner. Moreover, the overexpression of a transcriptional repressor form of CrebB rescued free-running locomotor rhythms in Smg5-depleted flies. These data demonstrate that CrebB is a rate-limiting substrate of the genetic NMD pathway important for the behavioral output of circadian clocks in Drosophila.


Assuntos
Relógios Circadianos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/genética , Mutação , Degradação do RNAm Mediada por Códon sem Sentido , Transativadores/metabolismo , Animais , Animais Geneticamente Modificados , Proteínas CLOCK/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Endorribonucleases/genética , Endorribonucleases/metabolismo , Neurônios/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Processamento Pós-Transcricional do RNA , Transdução de Sinais
8.
Can J Vet Res ; 83(2): 133-141, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31097875

RESUMO

Osteoarthritis, the leading cause of chronic joint pain, is studied through different animal models, but none of them is ideal in terms of reliability and translational value. In this pilot study of female rats, 3 surgical models of osteoarthritic pain, i.e., destabilization of the medial meniscus (DMM), cranial cruciate ligament transection (CCLT), and the combination of both surgical models (COMBO) and 1 chemical model [intra-articular injection of monosodium iodoacetate (MIA)] were compared for their impact on functional pain outcomes [static weight-bearing (SWB) and punctate tactile paw withdrawal threshold (PWT)] and spinal neuropeptides [substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), and somatostatin (SST)]. Six rats were assigned to each model group and a sham group. Both the chemical model (MIA) and surgical COMBO model induced functional alterations in SWB and PWT, with the changes being more persistent in the surgical combination group. Both models also produced an increase in levels of pro-nociceptive and anti-nociceptive neuropeptides at different timepoints. Pain comparison with the MIA model showed the advantage of a surgical model, especially the combination of the DMM and CCLT models, whereas each surgical model alone only led to temporary functional alterations and no change in neuropeptidomics.


Assuntos
Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Neuropeptídeos/metabolismo , Osteoartrite/etiologia , Dor/metabolismo , Animais , Feminino , Injeções Intra-Articulares , Medição da Dor , Projetos Piloto , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Suporte de Carga
9.
Int J Mol Sci ; 20(9)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086044

RESUMO

The central pacemakers of circadian timekeeping systems are highly robust yet adaptable, providing the temporal coordination of rhythms in behavior and physiological processes in accordance with the demands imposed by environmental cycles. These features of the central pacemaker are achieved by a multi-oscillator network in which individual cellular oscillators are tightly coupled to the environmental day-night cycle, and to one another via intercellular coupling. In this review, we will summarize the roles of various neurotransmitters and neuropeptides in the regulation of circadian entrainment and synchrony within the mammalian and Drosophila central pacemakers. We will also describe the diverse functions of protein kinases in the relay of input signals to the core oscillator or the direct regulation of the molecular clock machinery.


Assuntos
Ritmo Circadiano/fisiologia , Neuropeptídeos/metabolismo , Transdução de Sinais/fisiologia , Animais , Drosophila , Humanos , Camundongos , Núcleo Supraquiasmático/metabolismo
10.
Neuron ; 102(3): 529-552, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071288

RESUMO

The mesocorticolimbic pathway is canonically known as the "reward pathway." Embedded within the center of this circuit is the striatum, a massive and complex network hub that synthesizes motivation, affect, learning, cognition, stress, and sensorimotor information. Although striatal subregions collectively share many anatomical and functional similarities, it has become increasingly clear that it is an extraordinarily heterogeneous region. In particular, the nucleus accumbens (NAc) medial shell has repeatedly demonstrated that the rules dictated by more dorsal aspects of the striatum do not apply or are even reversed in functional logic. These discrepancies are perhaps most easily captured when isolating the functions of various neuromodulatory peptide systems within the striatum. Endogenous peptides are thought to play a critical role in modulating striatal signals to either amplify or dampen evoked behaviors. Here we describe the anatomical-functional backdrop upon which several neuropeptides act within the NAc to modulate behavior, with a specific emphasis on nucleus accumbens medial shell and stress responsivity. Additionally, we propose that, as the field continues to dissect fast neurotransmitter systems within the NAc, we must also provide considerable contextual weight to the roles local peptides play in modulating these circuits to more comprehensively understand how this important subregion gates motivated behaviors.


Assuntos
Motivação/fisiologia , Neuropeptídeos/metabolismo , Núcleo Accumbens/metabolismo , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Humanos , Interneurônios , Neurônios , Núcleo Accumbens/fisiologia
11.
Yakugaku Zasshi ; 139(5): 783-791, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31061348

RESUMO

This review focuses on the anti-dementia and antidepressant-like effects of peptides including glucagon-like peptide (GLP)-1, GLP-2, neuromedin U (NmU), and oxytocin, and the intranasal delivery of these peptides to the brain. Intracerebroventricularly administered GLP-1, NmU, and oxytocin improved impairment of learning and memory in mice treated with lipopolysaccharide or ß-amyloid protein. GLP-1 also improved impairment of learning and memory in juvenile diabetes model rats. On the other hand, GLP-2 exhibited antidepressant-like effects in mice during the forced-swim test, which were associated with 5-HT1A, α2, ß1, and D2 receptors. GLP-2 also exerted antidepressant-like effects in adrenocorticotropic hormone (ACTH)-treated mice through restoration of the hypothalamic-pituitary-adrenal-axis and neurogenesis in the subgranular zone of the dentate gyrus. Because intracerebroventricular administration is invasive and the peptides are unable to penetrate the blood-brain barrier, we introduced our new method of intranasal administration to deliver the peptides to the brain. We prepared a GLP-2 derivative containing cell-penetrating peptides (CPPs) and a penetration accelerating sequence (PAS). Intranasally administered PAS-CPPs-GLP-2 was distributed throughout the brain, and exhibited antidepressant-like effects in both naive and ACTH-treated mice. The derivatives of GLP-1, NmU, and oxytocin with the PAS and CPPs were also distributed throughout the brain after intranasal administration, and improved impairment of learning and memory. We confirmed that our peptide derivatives were effectively delivered into the brain by intranasal administration. As such, these derivatives may be useful for the clinical treatment of psychiatric and neurological diseases.


Assuntos
Administração Intranasal/métodos , Encéfalo/metabolismo , Demência/tratamento farmacológico , Depressão/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Peptídeos/metabolismo , Animais , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 2 Semelhante ao Glucagon/administração & dosagem , Peptídeo 2 Semelhante ao Glucagon/metabolismo , Humanos , Camundongos , Neuropeptídeos/administração & dosagem , Neuropeptídeos/metabolismo , Ocitocina/administração & dosagem , Ocitocina/metabolismo , Ratos
12.
Med Sci Monit ; 25: 2886-2895, 2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31002658

RESUMO

BACKGROUND Sleep deprivation (SD) is common in humans, and sleep loss has a significant influence on health and produces related diseases. Orexin-A has been demonstrated to play a role in physiological processes, including feeding, sleep/wake cycle, and energy metabolism. The aim of this study was to investigate the effect of SD on rats and to define the underlying mechanism. MATERIAL AND METHODS We constructed an SD rat model. The Morris water maze test was used to assess rat learning and memory. Imaging of hippocampus and hippocampal tissue in rats were captured by magnetic resonance imaging or electron microscopy. We used the CCK-8 kit to assess cell viability. The level of protein was measured using Western blot analysis, and qRT-PCR was used to evaluate mRNA level. RESULTS SD rats had poorer learning and memory and had damage to the hippocampus. SD resulted in shrinkage of hippocampal volume and encephalocele size. SD increased the expression of Orexin-A, OX1R, OX2R, and PARP-1, and decreased the expression of ERK1/2 and p-ERK1/2. Orexin-A (0-10 µM) improved neuron viability, whereas orexin-A (10-100 µM) attenuated neuron viability. SB334867 treatment reduced the viability of neurons treated with orexin-A. NU1025 treatment increased cell viability, especially in neurons treated with orexin-A. SB334867 treatment decreased the p-ERK1/2 levels in neurons treated with orexin-A. NU1025 increased the expression of p-ERK1/2 in neurons treated with orexin-A. CONCLUSIONS SD decreases learning and memory through damage to the hippocampus. Higher concentrations of orexin-A had a major negative effect on hippocampal neurons via OX1R and PARP-1 through inhibition of the ERK1/2 signaling pathway.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Privação do Sono/enzimologia , Animais , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Hipocampo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Memória/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Orexinas/metabolismo , Orexinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Privação do Sono/metabolismo
13.
Diabetes Res Clin Pract ; 151: 163-168, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31004673

RESUMO

AIMS: Neuromedin U (NMU), a highly conserved peptide, is implicated in energy homeostasis and is involved in regulating insulin secretion as a decretin hormone in animals. However, there have been no reports on the relationship between NMU and type 2 diabetes mellitus (T2DM). The aim of this study was to investigate circulating NMU concentrations in healthy subjects and T2DM patients and to evaluate the association between serum NMU levels and glucose-stimulated insulin secretion. METHODS: We used ELISA to analyze NMU concentrations in blood samples from newly diagnosed T2DM patients (n = 57) and age-, sex- and BMI-matched healthy control subjects (n = 50). Anthropometric parameters, oral glucose tolerance, glycosylated hemoglobin, blood lipids, insulin sensitivity, and insulin secretion were measured. RESULTS: No difference was observed in serum NMU levels between control subjects and newly diagnosed T2DM patients (p = 0.788). The oral glucose tolerance test (OGTT) results indicated that serum NMU concentrations did not change and did not correlate with insulin levels at fasting and 1 h, 2 h and 3 h after glucose load in both healthy controls and newly diagnosed T2DM patients. CONCLUSION: Circulating NMU concentrations were similar in control subjects and newly diagnosed T2DM patients and were not associated with glucose-stimulated insulin secretion. Serum NMU is not a human decretin hormone and may not play a role in the pathogenesis of T2DM.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Secreção de Insulina/fisiologia , Neuropeptídeos/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Neurochem Res ; 44(7): 1517-1532, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004261

RESUMO

Fibromyalgia is a chronic complex syndrome of non-articulate origin characterized by musculoskeletal pain, painful tender points, sleep problems and co-morbidities including depression, migraine. The etiopathogenesis of fibromyalgia is complex, variable and remains inconclusive. The etiological factors that have been defined include stress, genetic predisposition and environmental components. As per the reports of the American College of Rheumatology (ACR) the prevalence of fibromyalgia varies from 2 to 22% among the general population with poor diagnostic features primarily pain. Fibromyalgia encompasses a spectrum of co-morbid conditions with multifarious pathogenesis. The highly prevalent manifestations of fibromyalgia include heterogeneous pain and aches. Biochemical and neurobiological elements of fibromyalgia include neurotransmitters, hypothalamic pituitary adrenal axis (HPA axis), inflammatory cytokines, monoaminergic pathway, opioid peptides, sex hormones, nerve growth factor (NGF) and local free radical insult. An imbalance in the serotonergic system is the major underlying etiological factor that has been explored most widely. Owing to complex interplay of diverse pathophysiological pathways, overlapping co-morbidities such as depression have been clinically observed. Therapeutic management of fibromyalgia involves both non pharmacological and pharmacological measures. The current review presents various dysregulations and their association with symptoms of fibromyalgia along with their underlying neurobiological aspects.


Assuntos
Depressão/etiologia , Fibromialgia/etiologia , Hepatite C Crônica/etiologia , Doenças Inflamatórias Intestinais/etiologia , Transtornos de Enxaqueca/etiologia , Animais , Comorbidade , Citocinas/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Fibromialgia/metabolismo , Fibromialgia/fisiopatologia , Hepatite C Crônica/metabolismo , Hepatite C Crônica/fisiopatologia , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Neuropeptídeos/metabolismo , Estresse Oxidativo/fisiologia , Dor/metabolismo , Dor/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia
15.
Psychopharmacology (Berl) ; 236(5): 1597-1609, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30997526

RESUMO

The gut microbiota is comprised of a vast variety of microbes that colonize the gastrointestinal tract and exert crucial roles for the host health. These microorganisms, partially via their breakdown of dietary components, are able to modulate immune response, mood, and behavior, establishing a chemical dialogue in the microbiota-gut-brain interphase. Changes in the gut microbiota composition and functionality are associated with multiple diseases, in which altered levels of gut-associated neuropeptides are also detected. Gut neuropeptides are strong neuroimmune modulators; they mediate the communication between the gut microbiota and the host (including gut-brain axis) and have also recently been found to exert antimicrobial properties. This highlights the importance of understanding the interplay between gut neuropeptides and microbiota and their implications on host health. Here, we will discuss how gut neuropeptides help to maintain a balanced microbiota and we will point at the missing gaps that need to be further investigated in order to elucidate whether these molecules are related to neuropsychiatric disorders, which are often associated with gut dysbiosis and altered gut neuropeptide levels.


Assuntos
Encéfalo/imunologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/imunologia , Neuropeptídeos/imunologia , Animais , Anti-Infecciosos/efeitos adversos , Encéfalo/metabolismo , Disbiose/induzido quimicamente , Disbiose/imunologia , Disbiose/metabolismo , Trato Gastrointestinal/metabolismo , Humanos , Neuropeptídeos/metabolismo
16.
Toxicol Lett ; 310: 61-69, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31018152

RESUMO

PM2.5 is the main particulate air pollutant that is capable of inducing airway injury. Previous studies have indicated that Rac1 is involved in cigarette smoke-induced lung inflammation and lipopolysaccharide-mediated pulmonary injury. However, the contribution of Rac1 activity to PM2.5-induced lung inflammation remains largely unclear. Here, we investigated the regulation of Rac1 in PM2.5-induced inflammation in mouse airways and human bronchial epithelial cells (16HBE). The lungs of mice exposed to PM2.5 showed increased IL-1ß expression and an accumulation of inflammatory cells, thereby indicating high Rac1 activity. The exposure of 16HBE cells to PM2.5 resulted in elevated Rac1 levels, as well as an increased release of IL-1ß. Particularly, the selective inhibition of Rac1 ameliorated the IL-1ß release and inflammation in model lungs. Histological assessment showed that treatment with a Rac1 inhibitor, NSC23766, reduced the infiltration of neutrophils and macrophages into the airway lumen. Moreover, the selective inhibition or knockdown of Rac1 decreased IL-1ß release in 16HBE cells induced by PM2.5, which correlated with PM2.5-induced Rac1-regulated AKT signaling. Our data suggest an important role for Rac1 in the pathological alterations associated with PM2.5-mediated lung inflammation. Rac1 may be a promising therapeutic target for the treatment of the inflammatory diseases induced by PM2.5 inhalation.


Assuntos
Aminoquinolinas/farmacologia , Anti-Inflamatórios/farmacologia , Pulmão/efeitos dos fármacos , Neuropeptídeos/antagonistas & inibidores , Material Particulado/toxicidade , Pneumonia/prevenção & controle , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Animais , Linhagem Celular , Humanos , Exposição por Inalação/efeitos adversos , Interleucina-1beta/metabolismo , Pulmão/enzimologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos ICR , Neuropeptídeos/metabolismo , Tamanho da Partícula , Pneumonia/induzido quimicamente , Pneumonia/enzimologia , Pneumonia/patologia , Interferência de RNA , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
17.
Int J Mol Sci ; 20(7)2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30959962

RESUMO

Neurotensin and its high-affinity receptor, NTR1, are involved in the growth of various tumors. Few data are available regarding NTR1 expression in normal and tumoral human prostate tissue samples. NTR1 expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and 15 related metastatic lymph nodes (one per patient, when available). NTR1-staining was negative in normal prostate and BPH samples. NTR1 was overexpressed in four out of 44 (9.1%) primary tumors. There was no clear association between NTR1 overexpression and age, PSA-values, Gleason score, pT-status, nodal-status, or margin. NTR1 was expressed at a high level of five out of 15 (33.3%) metastatic lymph nodes. NTR1 overexpression was thus more frequent in metastatic lymph nodes than in primary tumors (p = 0.038). In this limited series of samples, NTR1 overexpression was observed in few primary prostate cancers. Upregulation was more frequent in related lymph nodes. The presence of this target in metastatic lymph nodes may open new perspectives for imaging and radionuclide therapy of prostate cancer. Factors driving NTR1 expression in primary prostate cancer and in nodal and distant metastases still need to be characterized.


Assuntos
Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Receptores de Neurotensina/metabolismo , Western Blotting , Células HT29 , Humanos , Técnicas In Vitro , Metástase Linfática/patologia , Masculino , Microscopia Confocal , Neuropeptídeos/metabolismo , Células PC-3 , Próstata/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Nat Med ; 25(4): 554-560, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30911133

RESUMO

The hippocampus is one of the most affected areas in Alzheimer's disease (AD)1. Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life2. This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry3,4. Nonetheless, direct evidence of AHN in humans has remained elusive. Thus, determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential. By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life. These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced. These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies.


Assuntos
Doença de Alzheimer/patologia , Hipocampo/patologia , Neurogênese , Adulto , Biomarcadores/metabolismo , Diferenciação Celular , Giro Denteado/patologia , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropeptídeos/metabolismo
19.
Cell Physiol Biochem ; 52(3): 455-467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873821

RESUMO

BACKGROUND/AIMS: Transient receptor potential canonical 6 (TRPC6) protein is a nonselective cation channel permitting the uptake of essential elements such as iron (Fe) and zinc (Zn). TRPC6 is found throughout the body with high expression levels in the placenta. However, its role in this organ is still to be determined. To further advance our understanding of the physiological relevance of TRPC6, we have studied the placental histology, pregnancy outcome and the Fe and Zn status of organs (placenta, brain, kidney, liver and lung) collected from TRPC6 deficient (TRPC6-/-) mice and sex and age-matched C57Bl6/J and B6129SF2/J mice. METHODS: Metal content was quantified by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Quantitative reverse transcriptase PCR (qRT-PCR) and Western Blottings (WB) were performed to analyze the expression of placental markers and TRPC6. RESULTS: Our data show that TRPC6-/- mice displayed reduced litter sizes, structural changes of the placenta, along with altered mRNA levels of CD31 and Gcm1, two markers of placental development. Furthermore, immunoblots revealed elevated amounts of TRPC6 proteins in placentas from women diagnosed with preeclampsia, a common gestational disease. When compared to C57Bl6/J and B6129SF2/J, TRPC6-/- mice had elevated Zn levels in placenta, liver and kidney during embryonic development and postnatally, but not at adulthood. High amounts of Fe were found in the adult brain and liver of TRPC6-/- mice. The lung was however not affected by the deletion of TRPC6, indicating that this mouse strain developed organ and age-dependent perturbations in their Zn and Fe status. CONCLUSION: This work indicates that TRPC6 exerts critical pathophysiological functions in placenta, and provides further evidence for a role of this channel in the homeostasis of cations like Zn and Fe.


Assuntos
Encéfalo/metabolismo , Ferro/metabolismo , Fígado/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/genética , Canais de Cátion TRPC/genética , Zinco/metabolismo , Adulto , Animais , Cátions Bivalentes , Feminino , Expressão Gênica , Homeostase/genética , Humanos , Transporte de Íons , Rim/metabolismo , Tamanho da Ninhada de Vivíparos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Canais de Cátion TRPC/deficiência
20.
Int J Dev Neurosci ; 74: 18-26, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822517

RESUMO

The decline in neurogenesis is a very critical problem in Alzheimer disease. Different biological activities have been reported for medicinal application of quercetin. Herein, we investigated the neurogenesis potential of quercetin in a rat model of Alzheimer's disease induced by amyloid-beta injection. Rats were randomly divided into Control, Alzheimer + Saline and Alzheimer + Quercetin groups. Following the administration of Amyloid-beta, rats in the Alzheimer + Quercetin group received 40 mg/kg/day quercetin orally for one month. Our data demonstrated amyloid-ß injection could impair learning and memory processing in rats indicated by passive avoidance test evaluation. We noted that one-month quercetin treatment alleviated the detrimental effects of amyloid-ß on spatial learning and memory parameters using Morris water maze analysis. Quercetin was found to increase the number of proliferating neural stem/progenitor cells. Notably, quercetin increased the number of DCX-expressing cells, indicating the active dynamic growth of neural progenitor cells in the dentate gyrus of the hippocampus. We further observed that the quercetin improved the number of BrdU/NeuN positive cells contributed to enhanced adult neurogenesis. Based on our results, quercetin had the potential to promote the expression of BDNF, NGF, CREB, and EGR-1 genes involved in regulating neurogenesis. These data suggest that quercetin can play a valuable role in alleviating Alzheimer's disease symptoms by enhancing adult neurogenesis mechanism.


Assuntos
Antioxidantes/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Giro Denteado/patologia , Transtornos de Aprendizagem/tratamento farmacológico , Células-Tronco Neurais/fisiologia , Neurogênese/efeitos dos fármacos , Quercetina/uso terapêutico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Giro Denteado/efeitos dos fármacos , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Transtornos de Aprendizagem/etiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Neuropeptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade , Ratos , Ratos Wistar
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