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1.
Sci Rep ; 9(1): 14290, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582799

RESUMO

The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI). Mesenteric nerve recordings were conducted in mice after treatment with SSRI to ascertain if this class of drugs resulted in increased vagal excitability. Patch clamp recordings of enteric neurons were carried out to measure activity of primary afferent neurons in the gut in response to SSRI and to assess the importance of gut epithelium in transducing signal. The tail suspension test (TST) was used following 14d feeding of SSRI in vagotomised and surgical sham mice to measure depressive-like behaviour. Brain mRNA expression was examined via PCR and the intestinal microbiome was assessed. Mesenteric nerve recordings in BALB/c mice demonstrated that oral treatment with SSRI leads to a significant increase in vagal activity. This effect was not observed in mice treated with a representative noradrenaline-dopamine reuptake inhibitor. It is known that signals from the gut can be transmitted to the vagus via the enteric nervous system. Exposure of the gut to SSRI increased the excitability of intrinsic primary afferent neurons in the myenteric plexus, through an intestinal epithelium dependent mechanism, and alpha-diversity of gut microbiota was altered. Critically, blocking vagal signaling from gut to brain, via subdiaphragmatic vagotomy, abolished the antidepressive effects of oral SSRI treatment as determined by the tail suspension test. This work suggests that vagus nerve dependent gut-brain signaling contributes to the effects of oral SSRI and further, highlights the potential for pharmacological approaches to treatment of mood disorders that focus on vagal stimulation and may not even require therapeutic agents to enter the circulation.


Assuntos
Encéfalo/efeitos dos fármacos , Sistema Nervoso Entérico/efeitos dos fármacos , Inibidores de Captação de Serotonina/farmacologia , Nervo Vago/efeitos dos fármacos , Administração Oral , Animais , Encéfalo/fisiologia , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/inervação , Sistema Nervoso Entérico/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Serotonina/metabolismo , Inibidores de Captação de Serotonina/administração & dosagem , Nervo Vago/fisiologia
2.
Development ; 145(9)2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29678817

RESUMO

The enteric nervous system (ENS) arises from neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the intestinal wall. Many extracellular matrix (ECM) components are present in the embryonic gut, but their role in regulating ENS development is largely unknown. Here, we identify heparan sulfate proteoglycan proteins, including collagen XVIII (Col18) and agrin, as important regulators of enteric neural crest-derived cell (ENCDC) development. In developing avian hindgut, Col18 is expressed at the ENCDC wavefront, while agrin expression occurs later. Both proteins are normally present around enteric ganglia, but are absent in aganglionic gut. Using chick-mouse intestinal chimeras and enteric neurospheres, we show that vagal- and sacral-derived ENCDCs from both species secrete Col18 and agrin. Whereas glia express Col18 and agrin, enteric neurons only express the latter. Functional studies demonstrate that Col18 is permissive whereas agrin is strongly inhibitory to ENCDC migration, consistent with the timing of their expression during ENS development. We conclude that ENCDCs govern their own migration by actively remodeling their microenvironment through secretion of ECM proteins.


Assuntos
Agrina/metabolismo , Proteínas Aviárias/metabolismo , Galinhas/metabolismo , Colágeno/metabolismo , Sistema Digestório , Crista Neural/embriologia , Nicho de Células-Tronco/fisiologia , Agrina/genética , Animais , Proteínas Aviárias/genética , Movimento Celular/fisiologia , Embrião de Galinha , Galinhas/genética , Colágeno/genética , Sistema Digestório/citologia , Sistema Digestório/embriologia , Sistema Digestório/inervação , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Camundongos , Crista Neural/citologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo
3.
Gastroenterology ; 154(5): 1249-1257, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29410117

RESUMO

Chronic digestive diseases, including irritable bowel syndrome, gastroesophageal reflux disease, and inflammatory bowel diseases, cannot be disentangled from their psychological context-the substantial burden of these diseases is co-determined by symptom and disease severity and the ability of patients to cope with their symptoms without significant interruption to daily life. The growing field of psychogastroenterology focuses on the application of scientifically based psychological principles and techniques to the alleviation of digestive symptoms. In this Clinical Practice Update, we describe the structure and efficacy of 2 major classes of psychotherapy-cognitive behavior therapy and gut-directed hypnotherapy. We focus on the impact of these brain-gut psychotherapies on gastrointestinal symptoms, as well as their ability to facilitate improved coping, resilience, and self-regulation. The importance of the gastroenterologist in the promotion of integrated psychological care cannot be overstated, and recommendations are provided on how to address psychological issues and make an effective referral for brain-gut psychotherapy in routine practice.


Assuntos
Encéfalo/fisiopatologia , Terapia Cognitivo-Comportamental/normas , Doenças do Sistema Digestório/terapia , Sistema Digestório/inervação , Gastroenterologia/normas , Hipnose , Benchmarking/normas , Doenças do Sistema Digestório/diagnóstico , Doenças do Sistema Digestório/fisiopatologia , Doenças do Sistema Digestório/psicologia , Medicina Baseada em Evidências/normas , Gastroenterologistas/normas , Humanos , Comunicação Interdisciplinar , Saúde Mental , Equipe de Assistência ao Paciente/normas , Psiquiatria/normas , Encaminhamento e Consulta , Fatores de Risco , Resultado do Tratamento
4.
Invert Neurosci ; 18(1): 2, 2018 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-29332202

RESUMO

The crustacean stomatogastric nervous system (STNS) is a well-known model for investigating neuropeptidergic control of rhythmic behavior. Among the peptides known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster, Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies were generated against one of the non-amidated peptides (AST-C I) and against the amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II antibody does not cross-react with either non-amidated peptide. Wholemount immunohistochemistry shows that both subclasses (non-amidated and amidated) of AST-C are distributed throughout the lobster STNS. Specifically, the antibody that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG). The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG, and two somata in the STG. Double immunolabeling shows that, except for one soma in each CoG, the non-amidated and amidated peptides are present in distinct sets of neuronal profiles. The differential distributions of the two AST-C subclasses suggest that the two peptide groups are likely to serve different modulatory roles in the lobster STNS.


Assuntos
Sistema Digestório/citologia , Sistema Digestório/inervação , Gânglios dos Invertebrados/metabolismo , Neuropeptídeos/metabolismo , Animais , Nephropidae/anatomia & histologia
5.
PLoS One ; 12(3): e0174172, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28334024

RESUMO

This study showed that in adult Drosophila melanogaster, the type of sugar-either present within the crop lumen or in the bathing solution of the crop-had no effect on crop muscle contraction. What is important, however, is the volume within the crop lumen. Electrophysiological recordings demonstrated that exogenous applications of serotonin on crop muscles increases both the amplitude and the frequency of crop contraction rate, while adipokinetic hormone mainly enhances the crop contraction frequency. Conversely, octopamine virtually silenced the overall crop activity. The present study reports for the first time an analysis of serotonin effects along the gut-brain axis in adult D. melanogaster. Injection of serotonin into the brain between the interocellar area shows that brain applications of serotonin decrease the frequency of crop activity. Based on our results, we propose that there are two different, opposite pathways for crop motility control governed by serotonin: excitatory when added in the abdomen (i.e., directly bathing the crop) and inhibitory when supplied within the brain (i.e., by injection). Finally, our results point to a double brain-gut serotonergic circuitry suggesting that not only the brain can affect gut functions, but the gut can also affect the central nervous system. On the basis of our results, and data in the literature, a possible mechanism for these two discrete serotonergic functions is suggested.


Assuntos
Encéfalo/efeitos dos fármacos , Sistema Digestório/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Hormônios de Inseto/farmacologia , Contração Muscular/efeitos dos fármacos , Octopamina/farmacologia , Oligopeptídeos/farmacologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Serotonina/farmacologia , Animais , Encéfalo/fisiologia , Sistema Digestório/inervação , Drosophila melanogaster/anatomia & histologia , Masculino , Contração Muscular/fisiologia , Ácido Pirrolidonocarboxílico/farmacologia
6.
J Exp Biol ; 218(Pt 18): 2905-17, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26206359

RESUMO

Many neuropeptides are members of peptide families, with multiple structurally similar isoforms frequently found even within a single species. This raises the question of whether the individual peptides serve common or distinct functions. In the accompanying paper, we found high isoform specificity in the responses of the lobster (Homarus americanus) cardiac neuromuscular system to members of the pyrokinin peptide family: only one of five crustacean isoforms showed any bioactivity in the cardiac system. Because previous studies in other species had found little isoform specificity in pyrokinin actions, we examined the effects of the same five crustacean pyrokinins on the lobster stomatogastric nervous system (STNS). In contrast to our findings in the cardiac system, the effects of the five pyrokinin isoforms on the STNS were indistinguishable: they all activated or enhanced the gastric mill motor pattern, but did not alter the pyloric pattern. These results, in combination with those from the cardiac ganglion, suggest that members of a peptide family in the same species can be both isoform specific and highly promiscuous in their modulatory capacity. The mechanisms that underlie these differences in specificity have not yet been elucidated; one possible explanation, which has yet to be tested, is the presence and differential distribution of multiple receptors for members of this peptide family.


Assuntos
Nephropidae/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Neuropeptídeos/farmacologia , Isoformas de Proteínas , Animais , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/inervação , Gânglios dos Invertebrados/efeitos dos fármacos , Gânglios dos Invertebrados/fisiologia , Contração Muscular/efeitos dos fármacos , Nephropidae/fisiologia , Isoformas de Proteínas/farmacologia
7.
Best Pract Res Clin Gastroenterol ; 28(6): 967-79, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25439064

RESUMO

The stomach has distinct functions in relation to the ingestion and handling of solids and liquids. These functions include storage of the food before it is gradually emptied into the duodenum, mechanical crushing of larger food particles to increase the surface area, secretion of an acidic enzyme rich gastric juice and mixing the ingested food with the gastric juice. In addition, the stomach 'senses' the composition of the gastric content and this information is passed via the vagal nerve to the lateral hypothalamus and the limbic system, most likely as palatability signals that influence eating behaviour. Other sensory qualities related to the stimulation of gastric tension receptors are satiety and fullness. Receptors that respond to macronutrient content or gastric wall tension influence appetite and meal related hormone responses. The ingestion of food - in contrast to an infusion of nutrients into the stomach - has distinct effects on the activation of specific brain regions. Brain areas such as thalamus, amygdala, putamen and praecuneus are activated by the ingestion of food. Gastric nutrient infusion evokes greater activation in the hippocampus and anterior cingulate. The brain integrates these interrelated neural and hormonal signals arising from the stomach as well as visual, olfactory and anticipatory stimuli that ultimately influence eating and other behavioural patterns. Furthermore, there is now good evidence from experimental studies that gastric afferents influence mood, and animal studies point towards the possibility that gastric dysfunction may be a risk factor for mood disorders such as anxiety and depression. The stomach is also not only colonised by Helicobacter pylori but a large array of bacteria. While there is sufficient evidence to suggest that H. pylori may alter caloric intake and mood, the role of other gastric microbiome for the brain function is unknown. To address this appropriate targeted gastric microbiome studies would be required instead of widely utilised opportunistic stool microbiome studies. In summary, it is now well established that there are important links between the brain and the stomach that have significant effects on gastric function. However, the stomach also influences the brain. Disturbances in the crosstalk between the stomach and the brain may manifest as functional GI disorders while disturbances in the stomach-brain communication may also result in an altered regulation of satiety and as a consequence may affect eating behaviour and mood. These observations may enable the identification of novel therapies targeted at the gastroduodenum that positively alter brain function and treat or prevent conditions such as obesity or functional gastrointestinal disorders.


Assuntos
Encéfalo/fisiologia , Transdução de Sinais/fisiologia , Estômago/fisiologia , Animais , Sistema Digestório/inervação , Gastroenteropatias/fisiopatologia , Humanos , Microbiota/fisiologia
8.
Elife ; 32014 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-25358089

RESUMO

Defecation allows the body to eliminate waste, an essential step in food processing for animal survival. In contrast to the extensive studies of feeding, its obligate counterpart, defecation, has received much less attention until recently. In this study, we report our characterizations of the defecation behavior of Drosophila larvae and its neural basis. Drosophila larvae display defecation cycles of stereotypic frequency, involving sequential contraction of hindgut and anal sphincter. The defecation behavior requires two groups of motor neurons that innervate hindgut and anal sphincter, respectively, and can excite gut muscles directly. These two groups of motor neurons fire sequentially with the same periodicity as the defecation behavior, as revealed by in vivo Ca(2+) imaging. Moreover, we identified a single mechanosensitive sensory neuron that innervates the anal slit and senses the opening of the intestine terminus. This anus sensory neuron relies on the TRP channel NOMPC but not on INACTIVE, NANCHUNG, or PIEZO for mechanotransduction.


Assuntos
Defecação/fisiologia , Drosophila melanogaster/fisiologia , Mecanotransdução Celular , Neurônios Motores/fisiologia , Células Receptoras Sensoriais/fisiologia , Potenciais de Ação/efeitos da radiação , Canal Anal/fisiologia , Canal Anal/efeitos da radiação , Animais , Axônios/metabolismo , Defecação/efeitos da radiação , Sistema Digestório/inervação , Sistema Digestório/efeitos da radiação , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/efeitos da radiação , Retroalimentação Fisiológica/efeitos da radiação , Processamento de Imagem Assistida por Computador , Larva/fisiologia , Larva/efeitos da radiação , Luz , Mecanotransdução Celular/efeitos da radiação , Modelos Neurológicos , Neurônios Motores/efeitos da radiação , Contração Muscular/efeitos da radiação , Mutação/genética , Fenótipo , Células Receptoras Sensoriais/efeitos da radiação
9.
Annu Rev Genet ; 47: 377-404, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24016187

RESUMO

The digestive tract plays a central role in the digestion and absorption of nutrients. Far from being a passive tube, it provides the first line of defense against pathogens and maintains energy homeostasis by exchanging neuronal and endocrine signals with other organs. Historically neglected, the gut of the fruit fly Drosophila melanogaster has recently come to the forefront of Drosophila research. Areas as diverse as stem cell biology, neurobiology, metabolism, and immunity are benefitting from the ability to study the genetics of development, growth regulation, and physiology in the same organ. In this review, we summarize our knowledge of the Drosophila digestive tract, with an emphasis on the adult midgut and its functional underpinnings.


Assuntos
Sistema Digestório/anatomia & histologia , Drosophila melanogaster/anatomia & histologia , Animais , Dieta , Digestão , Sistema Digestório/imunologia , Sistema Digestório/inervação , Sistema Digestório/microbiologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/imunologia , Drosophila melanogaster/fisiologia , Metabolismo Energético , Sistema Nervoso Entérico/fisiologia , Células Enteroendócrinas/fisiologia , Células Epiteliais/citologia , Hormônios Gastrointestinais/fisiologia , Interações Hospedeiro-Patógeno , Absorção Intestinal , Larva , Longevidade , Muco/fisiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-22526113

RESUMO

Previous in vitro and in vivo studies showed that the frequency of rhythmic pyloric network activity in the lobster is modulated directly by oxygen partial pressure (PO(2)). We have extended these results by (1) increasing the period of exposure to low PO(2) and by (2) testing the sensitivity of the pyloric network to changes in PO(2) that are within the narrow range normally experienced by the lobster (1 to 6 kPa). We found that the pyloric network rhythm was indeed altered by changes in PO(2) within the range typically observed in vivo. Furthermore, a previous study showed that the lateral pyloric constrictor motor neuron (LP) contributes to the O(2) sensitivity of the pyloric network. Here, we expanded on this idea by testing the hypothesis that pyloric pacemaker neurons also contribute to pyloric O(2) sensitivity. A 2-h exposure to 1 kPa PO(2), which was twice the period used previously, decreased the frequency of an isolated group of pacemaker neurons, suggesting that changes in the rhythmogenic properties of these cells contribute to pyloric O(2) sensitivity during long-term near-anaerobic (anaerobic threshold, 0.7-1.2 kPa) conditions.


Assuntos
Limiar Anaeróbio , Relógios Biológicos , Sistema Digestório/inervação , Nephropidae/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , Periodicidade , Potenciais de Ação , Animais , Nephropidae/anatomia & histologia , Rede Nervosa/metabolismo , Fatores de Tempo
13.
J Comp Neurol ; 519(13): 2658-76, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21491432

RESUMO

The crustacean stomatogastric ganglion (STG) is modulated by a large number of amines and neuropeptides that are found in descending pathways from anterior ganglia or reach the STG via the hemolymph. Among these are the allatostatin (AST) B types, also known as myoinhibitory peptides (MIPs). We used mass spectrometry to determine the sequences of nine members of the AST-B family of peptides that were found in the stomatogastric nervous system of the crab Cancer borealis. We raised an antibody against Cancer borealis allatostatin-B1 (CbAST-B1; VPNDWAHFRGSWa) and used it to map the distribution of CbAST-B1-like immunoreactivity (-LI) in the stomatogastric nervous system. CbAST-B1-LI was found in neurons and neuropil in the commissural ganglia (CoGs), in somata in the esophageal ganglion (OG), in fibers in the stomatogastric nerve (stn), and in neuropilar processes in the STG. CbAST-B1-LI was blocked by preincubation with 10(-6) M CbAST-B1 and was partially blocked by lower concentrations. Electrophysiological recordings of the effects of CbAST-B1, CbAST-B2, and CbAST-B3 on the pyloric rhythm of the STG showed that all three peptides inhibited the pyloric rhythm in a state-dependent manner. Specifically, all three peptides at 10(-8) M significantly decreased the frequency of the pyloric rhythm when the initial frequency of the pyloric rhythm was below 0.6 Hz. These data suggest important neuromodulatory roles for the CbAST-B family in the stomatogastric nervous system.


Assuntos
Braquiúros/anatomia & histologia , Braquiúros/metabolismo , Neuropeptídeos/metabolismo , Sequência de Aminoácidos , Animais , Sistema Digestório/inervação , Gânglios dos Invertebrados/citologia , Gânglios dos Invertebrados/metabolismo , Dados de Sequência Molecular , Neuropeptídeos/genética , Periodicidade
14.
Adv Ther ; 28(4): 279-94, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21437762

RESUMO

Adverse effects on the gastrointestinal system are problematic for pain patients receiving opioid treatment. Opioid-induced bowel dysfunction (OIBD) is often misinterpreted as constipation as this is the most frequently reported symptom of OIBD; however, it actually comprises the whole gut with symptoms such as nausea, reflux, bloating, and anorexia being very prevalent as well. Validated methods to evaluate these symptoms are essential before the action of a drug on bowel dysfunction can be evaluated, but only the effect on the most frequently reported symptom, constipation, has been evaluated systematically. Constipation is a personal symptom and there is little correlation between subjective methods for assessment of constipation and objective evaluations, such as transit time and fecal loading. Few questionnaires specific to constipation exist, since most that are regularly used form part of general gastrointestinal investigations, which furthermore are often complicated and time consuming to complete. This article gives an overview of the different evaluation regimes for OIBD with a particular focus on the most frequently reported symptom; constipation.


Assuntos
Analgésicos Opioides/efeitos adversos , Constipação Intestinal , Sistema Digestório , Sistema Nervoso Entérico/efeitos dos fármacos , Gastroenteropatias , Autorrelato/normas , Analgésicos Opioides/farmacocinética , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Constipação Intestinal/terapia , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/inervação , Sistema Digestório/fisiopatologia , Impacção Fecal/diagnóstico , Impacção Fecal/etiologia , Impacção Fecal/fisiopatologia , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Gastroenteropatias/terapia , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Absorção Intestinal/efeitos dos fármacos , Hipertonia Muscular/induzido quimicamente , Hipertonia Muscular/diagnóstico , Hipertonia Muscular/fisiopatologia , Qualidade de Vida , Padrões de Referência , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
15.
Neurosci Res ; 70(1): 55-61, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21291921

RESUMO

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a peptidergic neurotransmitter that is highly expressed in the nervous system. We have previously reported that a central injection of PACAP leads to changes in the autonomic nervous system tones including sympathetic excitation and parasympathetic inhibition. An anatomical study revealed that melanocortin and PACAP are colocalized in some hypothalamic nuclei. Here, we investigated the possible role of the melanocortin system in autonomic control by PACAP using SHU9119, an antagonist of the melanocortin receptors (MC3-R/MC4-R). Pretreatment with SHU-9119 did not affect the activating neural responses of adrenal, renal, and lumbar sympathetic nerves following a PACAP injection However, SHU9119 significantly eliminated the suppressing effect of a PACAP injection on gastric vagal nerve activity and excitation effects on liver and brown adipose tissue sympathetic nerve activities. These results suggest that the brain melanocortin system might play a key role in the control of thermogenic sympathetic outflows and digestive parasympathetic outflow by PACAP, but this system does not participate in the central effects of PACAP on cardiovascular function and neural activities of renal, adrenal, and lumbar sympathetic nerves.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Vias Autônomas/fisiologia , Hipotálamo/fisiologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Pró-Opiomelanocortina/fisiologia , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Vias Autônomas/efeitos dos fármacos , Sistema Digestório/inervação , Hipotálamo/efeitos dos fármacos , Masculino , Hormônios Estimuladores de Melanócitos/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Ratos , Ratos Wistar , Receptores de Melanocortina/antagonistas & inibidores , Receptores de Melanocortina/fisiologia , Fibras Simpáticas Pós-Ganglionares/efeitos dos fármacos , Fibras Simpáticas Pós-Ganglionares/fisiologia , Termogênese/fisiologia , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiologia , Vísceras/inervação , Vísceras/fisiologia
16.
Hum Genet ; 127(6): 675-83, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20361209

RESUMO

Hirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 x 10(-6) [OR = 3.32 (1.99, 5.59)] after replication. The HSCR-association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system.


Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos Par 9 , Doença de Hirschsprung/genética , Mapeamento Físico do Cromossomo/métodos , Proteínas Proto-Oncogênicas c-ret/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Sistema Digestório/inervação , Família , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Elongação da Transcrição , Distúrbios Congênitos do Ciclo da Ureia/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-19823843

RESUMO

Neuromodulation by peptides and amines is a primary source of plasticity in the nervous system as it adapts the animal to an ever-changing environment. The crustacean stomatogastric nervous system is one of the premier systems to study neuromodulation and its effects on motor pattern generation at the cellular level. It contains the extensively modulated central pattern generators that drive the gastric mill (chewing) and pyloric (food filtering) rhythms. Neuromodulators affect all stages of neuronal processing in this system, from membrane currents and synaptic transmission in network neurons to the properties of the effector muscles. The ease with which distinct neurons are identified and their activity is recorded in this system has provided considerable insight into the mechanisms by which neuromodulators affect their target cells and modulatory neuron function. Recent evidence suggests that neuromodulators are involved in homeostatic processes and that the modulatory system itself is under modulatory control, a fascinating topic whose surface has been barely scratched. Future challenges include exploring the behavioral conditions under which these systems are activated and how their effects are regulated.


Assuntos
Ritmo Circadiano/fisiologia , Sistema Digestório/inervação , Fenômenos Fisiológicos do Sistema Nervoso , Neurônios/fisiologia , Animais , Braquiúros/anatomia & histologia , Braquiúros/fisiologia , Gânglios dos Invertebrados/citologia , Gânglios dos Invertebrados/fisiologia , Modelos Neurológicos , Piloro/citologia
19.
Zh Evol Biokhim Fiziol ; 45(1): 110-21, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19370997

RESUMO

Localization and peculiarities of NO-ergic elements were studied for he first time throughout the entire length of digestive tract of the marine gastropod mollusc Achatina fulica (Prosobranchia) and the terrestrial molusc Littorina littorea (Pulmonata) by using histochemical method of detection of NADPH-diaphorase (NADPHd). NO-ergic cells and fibers were revealed in all parts of the mollusc digestive tract beginning from pharynx. An intensive NADPHd activity was found in many intraepithelial cells of the open type and in their processes in intra- and subepithelial nerve plexuses, single subepithelial neurons, granular connective tissue cells, and numerous nerve fibers among muscle elements of he digestive tract wall as well as in nerves innervating the tract. NADPHd was also present in receptor cells of he oral area and in the central A. fulica ganglia participating in innervation of the digestive tract. The digestive tract NO-ergic system ofA. fulica has a more complex organization that that of L. littorea. In the A. fulica pharynx, stomach, and midgut, directly beneath epithelium, there is revealed a complex system of glomerular structures formed by thin NADPHd-positive nerve fibers coming from the side of epithelium. More superficially under the main groups of muscle elements, small agglomerations of NADPHd-positive neurons are seen, which could be considered as primitive, non-formed microganglia. Peculiarities of distribution and a possible functional role of NO-ergic elements in the digestive tract of molluscs are discussed as compared with other invertebrate and vertebrate animals.


Assuntos
Sistema Digestório/enzimologia , Di-Hidrolipoamida Desidrogenase/metabolismo , Gastrópodes/enzimologia , Óxido Nítrico/metabolismo , Animais , Sistema Digestório/inervação , Gastrópodes/ultraestrutura
20.
J Vis Exp ; (25)2009 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-19308017

RESUMO

The stomatogastric ganglion (STG) is an excellent model for studying cellular and network interactions because it contains a relatively small number of cells (approximately 25 in C. borealis) which are well characterized. The cells in the STG exhibit a broad range of outputs and are responsible for the motor actions of the stomach. The stomach contains the gastric mill which breaks down food with three internal teeth, and the pylorus which filters the food before it reaches the midgut. The STG produces two rhythmic outputs to control the gastric mill and pylorus known as central pattern generators (CPGs). Each cell in the STG can participate in one or both of these rhythms. These CPGs allow for the study of neuromodulation, homeostasis, cellular and network variability, network development, and network recovery. The dissection of the stomatogastric nervous system (STNS) from the Jonah crab (Cancer borealis) is done in two parts; the gross and fine dissection. In the gross dissection the entire stomach is dissected from the crab. During the fine dissection the STNS is extracted from the stomach using a dissection microscope and micro-dissection tools (see figure 1). The STNS includes the STG, the oesophageal ganglion (OG), and the commissural ganglia (CoG) as well as the nerves that innervate the stomach muscles. Here, we show how to perform a complete dissection of the STNS in preparation for an electrophysiology experiment where the cells in the STG would be recorded from intracellularly and the peripheral nerves would be used for extracellular recordings. The proper technique for finding the desired nerves is shown as well as our technique of desheathing the ganglion to reveal the somata and neuropil.


Assuntos
Braquiúros/anatomia & histologia , Sistema Digestório/inervação , Dissecação/métodos , Sistema Nervoso/anatomia & histologia , Animais , Gânglios dos Invertebrados/anatomia & histologia , Microscopia/métodos
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