RESUMO
Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE.
Assuntos
Esofagite Eosinofílica/metabolismo , Esôfago/inervação , Azia/metabolismo , Gânglio Nodoso/metabolismo , Nervo Vago/metabolismo , Acrilamidas/farmacologia , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Capsaicina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esofagite Eosinofílica/induzido quimicamente , Esofagite Eosinofílica/fisiopatologia , Cobaias , Azia/induzido quimicamente , Azia/fisiopatologia , Concentração de Íons de Hidrogênio , Masculino , Potenciais da Membrana , Gânglio Nodoso/efeitos dos fármacos , Gânglio Nodoso/fisiopatologia , Gânglio Nodoso/cirurgia , Ovalbumina , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Fatores de Tempo , Vagotomia , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiopatologia , Nervo Vago/cirurgiaRESUMO
The jugular-nodose ganglia contain the sensory peripheral neurons of the vagus nerve, linking visceral organs to the medulla oblongata. Accessing these ganglia in smaller animals without damaging the vascular and neural structures may be challenging, as ganglionic fibers imbed deeply into the carotid sheath, and vagal parasympathetic fibers cross through the interior of the ganglia. We describe a practical protocol for locating and accessing the mouse jugular-nodose ganglia in vivo, including instructions for intraganglionic injections and postperfusion dissection. For complete details on the use and execution of this protocol, please refer to Han et al. (2018).
Assuntos
Dissecação/métodos , Gânglio Nodoso , Animais , Feminino , Forâmen Jugular/inervação , Masculino , Camundongos , Gânglio Nodoso/anatomia & histologia , Gânglio Nodoso/cirurgiaRESUMO
Vagal afferent neuron (VAN) signaling sends information from the gut to the brain and is fundamental in the control of feeding behavior and metabolism [1]. Recent findings reveal that VAN signaling also plays a critical role in cognitive processes, including affective motivational behaviors and hippocampus (HPC)-dependent memory [2-5]. VANs, located in nodose ganglia, express receptors for various gut-derived peptide signals; however, the function of these receptors with regard to feeding behavior, metabolism, and memory control is poorly understood. We hypothesized that VAN-mediated processes are influenced by ghrelin, a stomach-derived orexigenic hormone, via communication to its receptor (GHSR) expressed on gut-innervating VANs. To examine this hypothesis, rats received nodose ganglia injections of an adeno-associated virus (AAV) expressing short hairpin RNAs targeting GHSR (or a control AAV) for RNAi-mediated VAN-specific GHSR knockdown. Results reveal that VAN GHSR knockdown induced various feeding and metabolic disturbances, including increased meal frequency, impaired glucose tolerance, delayed gastric emptying, and increased body weight compared to controls. Additionally, VAN-specific GHSR knockdown impaired HPC-dependent contextual episodic memory and reduced HPC brain-derived neurotrophic factor expression, but did not affect anxiety-like behavior or general activity levels. A functional role for endogenous VAN GHSR signaling was further confirmed by results revealing that VAN signaling is required for the hyperphagic effects of ghrelin administered at dark onset, and that gut-restricted ghrelin-induced increases in VAN firing rate require intact VAN GHSR expression. Collective results reveal that VAN GHSR signaling is required for both normal feeding and metabolic function as well as HPC-dependent memory.
Assuntos
Grelina/metabolismo , Hipocampo/fisiologia , Gânglio Nodoso/metabolismo , Receptores de Grelina/metabolismo , Vias Aferentes/fisiologia , Animais , Peso Corporal/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Comportamento Alimentar/fisiologia , Esvaziamento Gástrico/fisiologia , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Fome/fisiologia , Masculino , Memória Episódica , Camundongos , Modelos Animais , Neurônios/metabolismo , Gânglio Nodoso/citologia , Gânglio Nodoso/cirurgia , Ratos , Ratos Transgênicos , Receptores de Grelina/genética , VagotomiaRESUMO
BACKGROUND: The anatomy and physiology of the pig nervous system is more similar to humans compared to traditional rodent models. This makes the pig an attractive model to answer questions relating to human health and disease. Yet the technical and molecular tools available to pig researchers are limited compared to rodent researchers. NEW METHOD: We developed simple and rapid methods to isolate the trigeminal, nodose (distal vagal), and dorsal root ganglia from neonatal pigs. We selected these ganglia due to their broad applicability to basic science researchers and clinicians. RESULTS: Use of these methods resulted in reproducible isolation of all three types of ganglia as validated by histological examination. COMPARISON WITH EXISTING METHOD(S): There are currently no methods that describe a step-by-step protocol to isolate these porcine ganglia. CONCLUSIONS: In conclusion, these methods for ganglia collection will facilitate and accelerate future neuroscience investigations in pig models of human disease.
Assuntos
Dissecação/métodos , Gânglios Espinais , Gânglio Nodoso , Suínos , Gânglio Trigeminal , Animais , Animais Recém-Nascidos , Feminino , Gânglios Espinais/citologia , Gânglios Espinais/cirurgia , Técnicas Histológicas , Masculino , Gânglio Nodoso/citologia , Gânglio Nodoso/cirurgia , Suínos/anatomia & histologia , Gânglio Trigeminal/citologia , Gânglio Trigeminal/cirurgiaRESUMO
We have previously shown that following unilateral nodose ganglionectomy, [125I] CGP42112 binds to a non-angiotensin II (Ang II) related binding site in rat dorsal motor nucleus of the vagus nerve, ambiguus nucleus and nucleus of the solitary tract. Furthermore, this up-regulated binding site localizes with activated microglia. Given that some tetracyclines may inhibit microglia activation in brain, we examined the effect of minocycline treatment on the binding of [125I] CGP42112 and [3H] PK11195 (an established radioligand for microglia), as well as OX-42 immunoreactivity (an immunomarker for activated microglia), following nodose ganglionectomy. Male Wistar Kyoto rats underwent unilateral nodose ganglionectomy or sham operation and were treated with saline or minocycline (50 mg/kg i.p.) 12 h before surgery and twice daily after surgery (each 50mg/kg i.p.) for 3 days. Subsequent to nodose ganglionectomy, [125I] CGP42112 binding (insensitive to PD123319 or Ang II) was increased approximately two-fold in the ipsilateral nucleus of the solitary tract and was also induced in the ipsilateral dorsal motor nucleus of the vagus nerve and ambiguus nucleus of saline-treated rats. Treatment with minocycline reduced this non-angiotensin II [125I] CGP42112 binding (40-50% reduction) in the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve and ambiguus nucleus. Analogous experiments using [3H] PK11195 also revealed up-regulated binding in the ipsilateral nucleus of the solitary tract ( approximately 205%), dorsal motor nucleus of the vagus nerve (approximately 80%) and ambiguus nucleus (approximately 210%) of saline-treated rats following nodose ganglionectomy, which was reduced by 40-100% with minocycline treatment. Immunoreactivity to OX-42 confirmed an increase in microglia activation and accumulation of macrophages in these brain stem nuclei following nodose ganglionectomy, which was also attenuated following treatment with minocycline. These data demonstrate that non-Ang II [125I] CGP42112 binding following nodose ganglionectomy is attenuated by minocycline treatment. This minocycline-induced effect was associated with reduced activation of microglia and an apparent reduction in the number of macrophages in the abovementioned nuclei. This evidence suggests that a non-Ang II [125I] CGP42112 binding site is located on, or associated with, activated microglia and macrophages, providing a useful tool with which to quantitate the neuroprotective effects of centrally acting anti-inflammatory compounds.
Assuntos
Antibacterianos/farmacologia , Tronco Encefálico/efeitos dos fármacos , Microglia/efeitos dos fármacos , Minociclina/farmacologia , Gânglio Nodoso/cirurgia , Oligopeptídeos/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Autorradiografia , Tronco Encefálico/metabolismo , Ganglionectomia , Imuno-Histoquímica , Isoquinolinas/farmacologia , Masculino , Microglia/metabolismo , Oligopeptídeos/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 2 de Angiotensina/metabolismoRESUMO
After lesions in the nucleus of the tractus solitarius (NTS) in cats and kittens, the termination of degenerating fibers was localized using the Nauta and the Fink-Heimer techniques. The distribution of degenerating fibers was compared with that seen after lesions of the dorsal nucleus of the vagus (DNV) and after section of the ninth and tenth cranial nerves. The projection from the NTS is to the nucleus ambiguus (A), the other divisions of the NTS including the medial NTS and the ventrolateral NTS, and DNV, the medial reticular formation ventral to the NTS (probably the paramedian reticular nucleus), the nucleus intercalatus (INC), and the intermediate nucleus (INT). The probable functional significance of projections from the NTS to these medullary nuclei is discussed in relation to pathways of cardiovascular reflexes. Of particular note is the projection to the INT which may be part of a descending pathway to spinal cardiovascular neurons in the intermediolateral horn.
Assuntos
Bulbo/anatomia & histologia , Fatores Etários , Animais , Gatos , Nervo Glossofaríngeo/anatomia & histologia , Bulbo/fisiologia , Vias Neurais/anatomia & histologia , Neurônios Aferentes/citologia , Gânglio Nodoso/cirurgia , Degeneração Retrógrada , Nervo Vago/anatomia & histologiaRESUMO
An anatomical basis was sought for the postulated roles of nitric oxide (NO) as a labile transcellular messenger in the dorsal vagal complex (NTS-X). The diaphorase activity of NO synthase was used as a marker of neurons in NTS-X that are presumed to convert L-arginine to L-citrulline and NO. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) staining patterns in the nucleus tractus solitarii (NTS) were spatially related to terminal sites of primary visceral afferents from 1) orosensory receptors (e.g., rostral-central nucleus); 2) soft palate, pharynx, larynx, and tracheobronchial tree (e.g., dorsal, intermediate, and interstitial nuclei); 3) esophagus (nucleus centralis); 4) stomach (nucleus gelatinosus); 5) hepatic and coeliac nerves (nucleus subpostrema); and 6) carotid body and baroreceptors (medial commissural and dorsal-lateral nuclei). Primary visceral afferents were identified as sources of NADPHd-stained fiber plexuses in the NTS-X based on three findings: 1) the presence of NADPHd in nodose ganglion cells with morphological features of first-order sensory relay neurons; 2) retrograde transport of Fluoro-Gold (FG) or cholera toxin B (CT-B) from NTS-X to NADPHd-positive nodose ganglion neurons; and 3) striking reductions of NADPHd-stained processes within primary vagal projection fields ipsilateral to unilateral nodose ganglionectomy. A central origin of NADPHd-stained processes in NTS-X was identified in the medial parvicellular subdivision of the paraventricular hypothalamic nucleus. We conclude that NO of peripheral and central origin may modulate viscerosensory signal processing in the NTS-X and autonomic reflex function.
Assuntos
Neurônios/enzimologia , Óxido Nítrico/metabolismo , Núcleo Solitário/enzimologia , Vísceras/inervação , Vias Aferentes , Animais , Especificidade de Anticorpos , Sistema Nervoso Autônomo/citologia , Sistema Nervoso Autônomo/enzimologia , Comunicação Celular/fisiologia , Membrana Celular/metabolismo , Colina O-Acetiltransferase/imunologia , Colina O-Acetiltransferase/metabolismo , Fibras Colinérgicas/enzimologia , Ganglionectomia , Histocitoquímica , Masculino , NADP/metabolismo , NADPH Desidrogenase/metabolismo , Neurônios/fisiologia , Óxido Nítrico Sintase/metabolismo , Gânglio Nodoso/enzimologia , Gânglio Nodoso/cirurgia , Ratos , Ratos Sprague-Dawley , Núcleo Solitário/citologia , Vísceras/citologiaRESUMO
The dorsal vagal complex of the medulla oblongata, comprising the nucleus tractus solitarii, the area postrema and the dorsal motor nucleus of the vagus nerve, is an important brainstem regulatory center for the autonomic nervous system. The major afferent input from abdominal and thoracic viscera to this region is via vagal sensory neurons which have their cell bodies in the nodose ganglion. Autoradiography has been used to study the effects of unilateral nodose ganglionectomy on receptor binding sites in this region of the brain for the neurotransmitters acetylcholine, norepinephrine, and opioids. Nodose ganglionectomy had no discernible effect on alpha 2 noradrenergic ([3H]p-aminoclonidine) or mu opioid [( 3H]Tyr-D-Ala-Gly-(NMePhe)-Gly-ol) binding sites. However, ganglionectomy did produce a 25% decrease in [3H]quinuclidinyl benzilate (muscarinic cholinergic) binding in the subnucleus gelatinosus of the solitary nucleus, and a marked decrease in [3H][D-Pen5]enkephalin (delta opioid) binding in the dorsomedial subnucleus of the nucleus tractus solitarii, ipsilateral to the lesion. These data suggest that muscarinic cholinergic and delta opioid receptors may be present on terminals of vagal afferent neurons that project to these specific brainstem regions. Since these vagal afferent neurons are known to arise, at least in part, from the gastrointestinal tract, it is possible that cholinergic and/or opioid receptors modulate specific autonomic functions associated with gastric sensory information such as satiety or nausea and emesis.
Assuntos
Bulbo/fisiologia , Gânglio Nodoso/fisiologia , Receptores Muscarínicos/metabolismo , Receptores Opioides/metabolismo , Nervo Vago/metabolismo , Nervo Vago/fisiologia , Animais , Gatos , Feminino , Masculino , Bulbo/metabolismo , Gânglio Nodoso/cirurgia , Receptores Opioides deltaRESUMO
Previously we reported that a non-angiotensin II [(125)I] CGP42112 binding site is up-regulated in rat brainstem nuclei as a result of unilateral nodose ganglionectomy. In the present study, we compared non-angiotensin II [(125)I] CGP42112 binding with microglia/macrophage activation following nodose ganglionectomy, using both in vitro autoradiography and immunohistochemistry. Specific [(125)I] CGP42112 binding was observed in the nucleus of the solitary tract (NTS) and revealed an AT(2) receptor component as well as a non-angiotensin II receptor component. Subsequent to unilateral nodose ganglionectomy, [(125)I] CGP42112 binding in the ipsilateral NTS was increased approximately two-fold and was also induced in the ipsilateral dorsal motor nucleus (DMX) and the nucleus ambiguus (n.amb). This non-angiotensin II [(125)I] CGP42112 binding site was displaced by CGP42112 but not other ligands. Increased [(3)H] PK11195 binding (a known marker of reactive gliosis) was also observed in the same brainstem nuclei as non-angiotensin II [(125)I] CGP42112 binding after nodose ganglionectomy. The similarity in binding patterns between [(125)I] CGP42112 and [(3)H] PK11195 was shown to be primarily due to retrograde degeneration in the ipsilateral NTS, DMX and n.amb, as both radioligands were localized to similar cellular targets within the interstial space and over cellular debris. Immunohistochemical data confirmed reactive gliosis within the ipsilateral NTS, DMX and n.amb, following nodose ganglionectomy, which was predominantly characterized by an increase in OX-42 immunoreactivity (a marker for activated microglia/macrophages), with only a small increase in glial fibrillary acidic protein immunoreactivity (a marker of astrogliosis) detected. These data demonstrate for the first time that non-angiotensin II [(125)I] CGP42112 binding is associated with activated microglia, as well as macrophages, following unilateral nodose ganglionectomy. Furthermore, these studies also demonstrate the potential use of non-angiotensin II [(125)I] CGP42112 binding as a marker for quantitating inflammatory events which occur as a result of damage to the CNS.
Assuntos
Angiotensina II/farmacologia , Tronco Encefálico/fisiopatologia , Gânglio Nodoso/fisiologia , Oligopeptídeos/farmacologia , Vasoconstritores/farmacologia , Angiotensina II/análogos & derivados , Angiotensina II/metabolismo , Animais , Autorradiografia , Biomarcadores , Tronco Encefálico/patologia , Ganglionectomia , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Gliose/fisiopatologia , Radioisótopos do Iodo , Isoquinolinas/metabolismo , Isoquinolinas/farmacologia , Masculino , Microglia/fisiologia , Gânglio Nodoso/cirurgia , Oligopeptídeos/metabolismo , Ratos , Ratos Endogâmicos WKY , Trítio , Vasoconstritores/metabolismoRESUMO
Substance P (SP) regulates visceral functions in the nucleus of the solitary tract (NST) area. High affinity SP binding sites labelled with [3H]SP or [125I]SP show a heterogeneous distribution in the cat medulla with high densities in the rostral and dorso-caudal parts of both the median subnucleus of NST and the dorsal motor nucleus (DMN). We previously observed a significant loss of SP immunoreactivity in the vagal area of the cat after an ipsilateral nodosectomy. It was thus important to study the correlated plasticity of SP binding in the context of the regulation of receptor function. Whichever labelled ligand was used, a unilateral nodose excision was followed by an ipsilateral increase in SP binding in the NST (200%) and the DMN (300%) after 30 days of survival. This increase was region-specific and did not match exactly the decrease in SP immunoreactivity following nodosectomy. This SP receptor density up-regulation could be due to long-term deprivation of SP afferent fibres in the NST and partly in the DMN. In the latter the increase of SP receptors occurred in both the cytoplasm of large neurons and the neuropile and did not affect the glia. The up-regulation phenomenon seems to be specific for SP receptors in the cat (at least in the DMN) and may constitute a reactive mechanism against the injury of axotomy of DMN neurons.
Assuntos
Tronco Encefálico/metabolismo , Receptores de Neurotransmissores/metabolismo , Substância P/metabolismo , Regulação para Cima , Sequência de Aminoácidos , Animais , Autorradiografia , Sítios de Ligação , Tronco Encefálico/anatomia & histologia , Gatos , Denervação , Gânglios Espinais/química , Gânglios Espinais/metabolismo , Dados de Sequência Molecular , Plasticidade Neuronal , Gânglio Nodoso/cirurgia , Receptores da Neurocinina-1 , Nervo VagoRESUMO
We have examined the binding distribution of a selective AT(2) receptor ligand [125I] CGP42112 in the brain of adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). AT(2) receptor localization was also examined in the rat brainstem following unilateral nodose ganglionectomy. Specific [125I] CGP42112 binding was observed in discrete brain regions from both rat strains, including the nucleus of the solitary tract (NTS), and did not differ between WKY and SHR. [125I] CGP42112 binding in the NTS revealed an AT(2) receptor component that was displaceable by PD 123319 and Ang II (50-58%), as well as a non-angiotensin II receptor component (42-49%). Following unilateral nodose ganglionectomy, [125I] CGP42112 binding density on the denervated side of the NTS was increased approximately two-fold in both WKY and SHR. This increased [125I] CGP42112 binding density in the ipsilateral NTS was comprised of a greater non-angiotensin II component than that observed in the sham groups, since only approximately 30% was displaced by PD123319 and angiotensin II. Furthermore, [125I] CGP42112 also revealed high binding density on the denervated side in the dorsal motor nucleus and the nucleus ambiguus in both WKY and SHR. AT(2) receptor immunoreactivity was also visualised in the NTS of sham operated rats, but was not observed in the dorsal motor nucleus or the nucleus ambiguus, nor was it up-regulated following nodose ganglionectomy. These results demonstrate, for the first time, an AT(2) receptor binding site in the NTS, as well as a non-angiotensin II [125I] CGP42112 binding site. These studies also demonstrate that nodose ganglionectomy represents a useful model in which to study a non-angiotensin II [125I] CGP42112 binding site that is up-regulated following degeneration of afferent vagal nerves.
Assuntos
Oligopeptídeos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Receptores de Angiotensina/metabolismo , Núcleo Solitário/metabolismo , Angiotensina II/análogos & derivados , Angiotensina II/farmacocinética , Antagonistas de Receptores de Angiotensina , Animais , Anti-Hipertensivos/farmacocinética , Autorradiografia , Ligação Competitiva , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Lateralidade Funcional , Ganglionectomia/métodos , Imidazóis/farmacocinética , Imuno-Histoquímica , Radioisótopos do Iodo , Losartan/farmacocinética , Masculino , Gânglio Nodoso/cirurgia , Piridinas/farmacocinética , Ensaio Radioligante , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Núcleo Solitário/fisiopatologiaRESUMO
The present study reports the results of physiological and anatomical experiments in which the purpose was to determine whether desheathing the nodose ganglion is a reliable method of vagal de-efferentation in the ferret. In physiological studies, the effects of electrically stimulating the treated and untreated vagal nerves on cardiovascular and intestinal responses were examined and compared with previously obtained data after left supranodose vagotomy. The anatomical studies illustrated the effects of desheathing the left nodose ganglion on the transport of horseradish peroxidase (HRP) within a thoracic vagal communicating branch. These data were compared to data from control animals and animals that had undergone left supranodose vagotomy. The results demonstrated that severing the fascicles overlying the left nodose ganglion and allowing the nerve fibers to degenerate, caused no reduction in labeled efferent cell bodies in the left dorsal motor nucleus of the vagus as compared to controls. However, after left supranodose vagotomy there were no efferent cell bodies labeled in the left dorsal motor nucleus of the vagus. Following degeneration of the fascicles, electrical stimulation of the peripheral cut end of this nerve did not abolish the efferent responses in 7 out of 9 animals studied, whereas supranodose vagotomy abolished the responses in all animals. These findings demonstrate that desheathing the nodose ganglion and thereby removing the nerve bundles overlying the nodose ganglion is not a guaranteed method of destroying the efferent fibers in the vagus nerve of the ferret. Supranodose vagotomy, therefore, is a more reliable method of de-efferentation in this species.
Assuntos
Carnívoros/cirurgia , Furões/cirurgia , Neurônios Eferentes/cirurgia , Gânglio Nodoso/cirurgia , Vagotomia/veterinária , Nervo Vago/cirurgia , Animais , Estimulação Elétrica , Feminino , Furões/anatomia & histologia , Peroxidase do Rábano Silvestre , Masculino , Gânglio Nodoso/anatomia & histologia , Gânglio Nodoso/fisiologia , Vagotomia/métodosRESUMO
The vagus nerve innervates visceral organs providing a link between key metabolic cues and the CNS. However, it is not clear whether vagal neurons can directly respond to changing lipid levels and whether altered "lipid sensing" by the vagus nerve regulates energy balance. In this study, we systematically profiled the expression of all known nuclear receptors in laser-captured nodose ganglion (NG) neurons. In particular, we found PPARγ expression was reduced by high-fat-diet feeding. Deletion of PPARγ in Phox2b neurons promoted HFD-induced thermogenesis that involved the reprograming of white adipocyte into a brown-like adipocyte cell fate. Finally, we showed that PPARγ in NG neurons regulates genes necessary for lipid metabolism and those that are important for synaptic transmission. Collectively, our findings provide insights into how vagal afferents survey peripheral metabolic cues and suggest that the reduction of PPARγ in NG neurons may serve as a protective mechanism against diet-induced weight gain.
Assuntos
Dieta Hiperlipídica , Metabolismo dos Lipídeos/fisiologia , Neurônios/metabolismo , Gânglio Nodoso/citologia , PPAR gama/metabolismo , Termogênese/fisiologia , Adipócitos/citologia , Animais , Diferenciação Celular/fisiologia , Deleção de Genes , Regulação da Expressão Gênica/fisiologia , Microdissecção e Captura a Laser , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Neurônios/fisiologia , Gânglio Nodoso/cirurgia , PPAR gama/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The N-methyl-D-aspartate (NMDA) ion channel blocker MK-801 administered systemically or as a nanoliter injection into the nucleus of the solitary tract (NTS), increases meal size. Furthermore, we have observed that ablation of the NTS abolishes increased meal size following systemic injection of dizocilpine (MK-801) and that MK-801-induced increases in intake are attenuated in rats pretreated with capsaicin to destroy small, unmyelinated, primary afferent neurons. These findings led us to hypothesize that NMDA receptors on central vagal afferent terminals or on higher-order NTS neurons innervated by these vagal afferents might mediate increased food intake. To evaluate this hypothesis, we examined 15% sucrose intake after 50-nl MK-801 injections ipsilateral or contralateral to unilateral nodose ganglion removal (ganglionectomy). On the side contralateral to ganglionectomy, vagal afferent terminals would be intact and functional, whereas ipsilateral to ganglionectomy vagal afferent terminals would be absent. Three additional control preparations also were included: 1) sham ganglionectomy and 2) subnodose vagotomy either contralateral or ipsilateral to NTS cannula placement. We found that rats with subnodose vagotomies increased their sucrose intake after injections of MK-801 compared with saline, regardless of whether injections were made contralateral (12.6 +/- 0.2 vs. 9.6 +/- 0.3 ml) or ipsilateral (14.2 +/- 0.6 vs. 9.7 +/- 0.4 ml) to vagotomy. Rats with NTS cannula placements contralateral to nodose ganglionectomy also increased their intake after MK-801 (12.2 +/- 0.9 and 9.2 +/- 1.1 ml for MK-801 and saline, respectively). However, rats with placements ipsilateral to ganglionectomy did not respond to MK-801 (8.0 +/- 0.5 ml) compared with saline (8.3 +/- 0.4 ml). We conclude that central vagal afferent terminals are necessary for increased food intake in response to NMDA ion channel blockade. The function of central vagal afferent processes or the activity of higher-order NTS neurons driven by vagal afferents may be modulated by NMDA receptors to control meal size.
Assuntos
Apetite/fisiologia , Ingestão de Alimentos/fisiologia , Neurônios Aferentes/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Resposta de Saciedade/fisiologia , Nervo Vago/fisiologia , Animais , Apetite/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Gânglio Nodoso/citologia , Gânglio Nodoso/metabolismo , Gânglio Nodoso/cirurgia , Ratos , Ratos Sprague-Dawley , Núcleo Solitário/fisiologia , Nervo Vago/cirurgiaRESUMO
Prolongation of the QT interval in the ECG can be induced in d 17 chick embryos by ablating the nodose placode on the right side on d 1 of development. The nodose placode contains the precursor cells which form the neurons of the nodose (inferior vagal) ganglion. Neurons in this ganglion provide sensory innervation to the heart and other viscera. In this study, we measured ganglion volume and neuron size and number in the right and left nodose ganglia in d 17 experimental and control embryos from whom electrocardiograms had been obtained. A significant reduction in the number of neurons present in the right nodose ganglion, relative to the left ganglion, was evident in all embryos with abnormally prolonged QT intervals. Embryos with prolonged QT, as well as lesioned embryos who demonstrated normal.QT on d 17, also had abnormally small neurons in both right and left nodose ganglia, indicating an additional nonspecific, perhaps permissive, effect of the lesion. These results suggest that abnormal development of the sensory innervation of the heart may be an important link in the chain of events leading to the developmental long QT syndrome expressed by these embryos.
Assuntos
Coração/inervação , Síndrome do QT Longo/fisiopatologia , Gânglio Nodoso/cirurgia , Animais , Embrião de Galinha , Modelos Animais de Doenças , Frequência Cardíaca , Gânglio Nodoso/citologiaRESUMO
The nodose ganglion is the distal cranial ganglion of the vagus nerve which provides sensory innervation to the heart and other viscera. In this study, removal of the neuronal precursors which normally populate the right nodose ganglion was accomplished by ablating the right nodose placode in stage 9 chick embryos. Subsequent histological evaluation showed that in 54% of lesioned embryos surviving to day 6, the right ganglion was absent. Most embryos surviving to day 12, however, had identifiable right ganglia. In day 12 embryos, the right ganglion which developed was abnormal, with ganglion volume and ganglion cell diameter reduced by 50% and 20%, respectively, compared to control ganglia. To investigate the source of the neuron population in the regenerated ganglion, we combined nodose placode ablation with bilateral replacement of chick with quail "cardiac" neural crest (from mid-otic placode to somite 3). These cells normally provide only non-neuronal cells to the nodose ganglion, but produce neurons in other regions. At day 9, quail-derived neurons were identified in the right nodose ganglia of these chimeras, indicating that cardiac neural crest cells can generate neurons in the ganglion when placode-derived neurons are absent or reduced in number. On the other hand, we found that "sympathetic" neural crest (from somites 10 to 20) does not support ganglion development, suggesting that only neural crest cells normally present in the ganglion participate in reconstituting its neuronal population. Our previous work has shown that right nodose placode ablation produces abnormal cardiac function, which mimics a life-threatening human heart condition known as long QT syndrome. The present results suggest that the presence of neural crest-derived neurons in the developing right nodose ganglion may contribute to the functional abnormality in long QT syndrome.
Assuntos
Gânglio Nodoso/embriologia , Animais , Embrião de Galinha , Denervação , Crista Neural/citologia , Crista Neural/transplante , Gânglio Nodoso/cirurgia , Gânglio Nodoso/ultraestrutura , Células-Tronco , Transplante de TecidosRESUMO
These first ultrastructural studies of the effect caused by thermocoagulation of a ganglion (ganglion inferius nervi vagi) akin to the Gasserian ganglion have shown that selective pain fiber elimination can only be expected from thermocoagulation at temperatures not higher than 50 degrees C/60 s or 60 degrees C/60 s. Even if the results of these animal experiments can only be applicable to clinical practice in the sense of an analogical conclusion, we are nevertheless of the opinion that it can be recommended to begin the thermocoagulation in trigeminus neuralgia at low temperatures (50 degrees C/60 s or 60 degrees C/60 s) and only if found necessary, after checking the sensitivity to pain, to increase it in steps of 5--10 degrees C.
Assuntos
Gânglio Trigeminal/cirurgia , Nervo Trigêmeo/cirurgia , Neuralgia do Trigêmeo/cirurgia , Animais , Eletrocoagulação , Humanos , Gânglio Nodoso/cirurgia , Coelhos , TemperaturaRESUMO
A case of a 47-years-old female patient treated for a vagal body tumor is presented. The origin, clinical appearance and special diagnostic and therapeutic problems created by this rare tumor are discussed.
Assuntos
Neoplasias dos Nervos Cranianos/patologia , Gânglio Nodoso/patologia , Paraganglioma/patologia , Nervo Vago/patologia , Neoplasias dos Nervos Cranianos/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Gânglio Nodoso/cirurgia , Paraganglioma/cirurgiaRESUMO
BACKGROUND: The ultrastructure of the vagal and spinal accessory nerves was studied 1) in normal sheep and 2) in sheep in which an experimental crossed-nerve anastomosis had been made by sectioning the supranodose vagal and spinal accessory nerves, then suturing the distal end of the vagal nerve to the distal end of the spinal accessory nerve, and allowing time for regeneration to occur. This study was carried out in order to analyze the modifications liable to occur when this technique is used and to specify the origin and the nature of the fibers that colonize the spinal accessory nerve. METHODS: The study was performed in 4- to 5-month-old-sheep. After the surgical procedure, the animals were housed indoors during 1 year until their sacrifice by fixative perfusion. Then, nerve samples were dissected out, processed for electron microscopy, examined, and systematically photographed. After printing, the diameters of the nerve fibers were determined. RESULTS: In sheep, the ratios of nonmyelinated to myelinated fibers (NF/MF) in the infranodose and supranodose vagal nerve and accessory spinal nerve were 1.21, 1.67, and 3.21, respectively. In both parts of the vagal nerve, the myelinated fibers had a unimodal diameter distribution around a peak of 4 microns; whereas, in the spinal accessory nerve, they were distributed bimodally, and 53% had values of 15-18 microns. After making the above anastomosis, the centrifugal vagal fibers degenerated, and the NF/MF ratios increased in the centripetal infranodose vagal nerve, in the reinnervating supranodose vagal nerve, and in the reinnervated spinal accessory nerve (approximately 1.87, 1.72, and 6.04, respectively). In all of these nerves, the myelinated fibers had a unimodal distribution with a peak at 4 microns, as in the vagal nerve of normal sheep. CONCLUSIONS: These results reveal the large part taken by the nonmyelinated fibers in the nerve fiber population of the vagal nerve and support the vagal origin of the fibers reinnervating the spinal accessory nerve.
Assuntos
Nervo Acessório/cirurgia , Nervo Acessório/ultraestrutura , Ovinos/anatomia & histologia , Nervo Vago/cirurgia , Nervo Vago/ultraestrutura , Nervo Acessório/fisiologia , Anastomose Cirúrgica , Animais , Microscopia Eletrônica , Fibras Nervosas/ultraestrutura , Fibras Nervosas Mielinizadas/ultraestrutura , Regeneração Nervosa , Gânglio Nodoso/fisiologia , Gânglio Nodoso/cirurgia , Gânglio Nodoso/ultraestrutura , Nervo Vago/fisiologiaRESUMO
The cardiovascular effects of substance P (SP) microinjections in the nucleus tractus solitarii (NTS) were evaluated in conscious rats. We chose this model because it is an effective way to access some of the cardiovascular effects of neurotransmitters in the NTS without the inconvenience of blunting pathways with anesthetic agents or removing forebrain projections by decerebration. The cardiovascular responses to SP injections were also evaluated after chronic nodose ganglionectomy. We found that, in conscious rats, SP microinjections into the NTS induced hypertension and tachycardia. Unilateral and bilateral SP injections into the NTS caused a slow increase in blood pressure and heart rate that peaked 1.5-5 min after injection and lasted for 20-30 min. Nodose ganglionectomy increased the duration of the pressor and tachycardic effects of SP and enhanced the pressor response. These data show that SP in the NTS is involved in pressor pathways. The supersensitivity to SP seen after nodose ganglionectomy suggests that vagal afferent projections are involved in those pressor pathways activated by SP in the NTS.