RESUMO
Pomacea canaliculata is an invasive snail species causing major problems in agriculture. The snail biology was then investigated. The main objective of the present study was to investigate the nervous system of the snail. The nervous system comprises pairs of cerebral, buccal, pedal, pleural, parietal ganglia and an unpaired visceral ganglion. Most neurons were concentrated at the periphery of the ganglia. The neurons were classified into four types: NR1, NR2, NR3, and NR4. The percentages of the NR3 and NR4 in the pleural and pedal ganglia were significantly higher than those of other ganglia. Ultrastructural study revealed that nuclei of all neuronal types exhibited mostly euchromatins. Many organelles including ribosomes and endoplasmic reticulum were found in their cytoplasm. However, various mitochondria were found in the NR2 and NR3. The immunohistochemistry revealed immunoreactivity of ghrelin-like peptide in the neurons of the cerebral, pleural and pedal ganglia. However, immunoreactivity of GHS-R1a-like peptide existed only in the neurons of the pleural and pedal ganglia. The present study is the first to demonstrate the existence of ghrelin-like peptide and its receptor in P. canaliculata nervous system.
Assuntos
Neurônios , Caramujos , Animais , Caramujos/metabolismo , Caramujos/ultraestrutura , Neurônios/metabolismo , Neurônios/ultraestrutura , Grelina/metabolismo , Gânglios dos Invertebrados/metabolismo , Gânglios dos Invertebrados/ultraestrutura , Gânglios/metabolismo , Gânglios/ultraestruturaRESUMO
The inner ear sensory neurons play a pivotal role in auditory processing and balance control. Though significant progresses have been made, the underlying mechanisms controlling the differentiation and survival of the inner ear sensory neurons remain largely unknown. During development, ISL1 and POU4F transcription factors are co-expressed and are required for terminal differentiation, pathfinding, axon outgrowth and the survival of neurons in the central and peripheral nervous systems. However, little is understood about their functional relationship and regulatory mechanism in neural development. Here, we have knocked out Isl1 or Pou4f1 or both in mice of both sexes. In the absence of Isl1, the differentiation of cochleovestibular ganglion (CVG) neurons is disturbed and with that Isl1-deficient CVG neurons display defects in migration and axon pathfinding. Compound deletion of Isl1 and Pou4f1 causes a delay in CVG differentiation and results in a more severe CVG defect with a loss of nearly all of spiral ganglion neurons (SGNs). Moreover, ISL1 and POU4F1 interact directly in developing CVG neurons and act cooperatively as well as independently in regulating the expression of unique sets of CVG-specific genes crucial for CVG development and survival by binding to the cis-regulatory elements including the promoters of Fgf10, Pou4f2, and Epha5 and enhancers of Eya1 and Ntng2 These findings demonstrate that Isl1 and Pou4f1 are indispensable for CVG development and maintenance by acting epistatically to regulate genes essential for CVG development.
Assuntos
Orelha Interna , Regulação da Expressão Gênica no Desenvolvimento , Animais , Feminino , Masculino , Camundongos , Gânglios/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Células Receptoras Sensoriais/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
IMPORTANCE: Herpes simplex virus 1 is an important human pathogen that has been intensively studied for many decades. Nevertheless, the molecular mechanisms regulating its establishment, maintenance, and reactivation from latency are poorly understood. Here, we show that HSV-1-encoded miR-H2 is post-transcriptionally edited in latently infected human tissues. Hyperediting of viral miRNAs increases the targeting potential of these miRNAs and may play an important role in regulating latency. We show that the edited miR-H2 can target ICP4, an essential viral protein. Interestingly, we found no evidence of hyperediting of its homolog, miR-H2, which is expressed by the closely related virus HSV-2. The discovery of post-translational modifications of viral miRNA in the latency phase suggests that these processes may also be important for other non-coding viral RNA in the latency phase, including the intron LAT, which in turn may be crucial for understanding the biology of this virus.
Assuntos
Herpes Simples , Herpesvirus Humano 1 , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Herpesvirus Humano 1/fisiologia , Latência Viral/genética , Proteínas Virais/metabolismo , Gânglios/metabolismo , Gânglio Trigeminal , Ativação Viral/genéticaRESUMO
Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) infect and establish latency in neurons of the peripheral nervous system to persist lifelong in the host and to cause recurrent disease. During primary infection, HSV replicates in epithelial cells in the mucosa and skin and then infects neurites, highly dynamic structures that grow or retract in the presence of attracting or repelling cues, respectively. Following retrograde transport in neurites, HSV establishes latency in the neuronal nucleus. Viral and cellular proteins participate in the chromatinization of the HSV genome that regulates gene expression, persistence, and reactivation. HSV-2 modulates neurite outgrowth during primary infection and upon reactivation, probably to facilitate infection and survival of neurons. Whether HSV-1 modulates neurite outgrowth and the underlying mechanism is currently under investigation. This review deals with HSV-1 and HSV-2 colonization of peripheral neurons, with a focus on the modulation of neurite outgrowth by these viruses.
Assuntos
Herpes Simples , Herpesvirus Humano 1 , Humanos , Herpesvirus Humano 1/genética , Gânglios/metabolismo , Latência ViralRESUMO
The aganglionic bowel in short-segment Hirschsprung's disease is characterized both by the absence of enteric ganglia and the presence of extrinsic thickened nerve bundles (TNBs). The relationship between the TNBs and the loss of enteric ganglia is unknown. Previous studies have described decreasing numbers of ganglia with increasing density of TNBs within the transition zone (TZ) between ganglionic and aganglionic gut, and there is some evidence of spatial contact between them in this region. To determine the cellular interactions involved, we have analysed the expression of perineurial markers of TNBs and enteric ganglionic markers for both neural cells and their ensheathing telocytes across four cranio-caudal segments consisting of most proximal ganglionic to most distal aganglionic from pull-through resected colon. We show that in the TZ, enteric ganglia are abnormal, being surrounded by perineurium cells characteristic of TNBs. Furthermore, short processes of ganglionic neurons extend caudally towards the aganglionic region, where telocytes in the TNB are located between the perineurium and nerve fibres into which they project telopodes. Thus, enteric ganglia within the TZ have abnormal structural characteristics, the cellular relationships of which are shared by the TNBs. These findings will help towards elucidation of the cellular mechanisms involved in the aetiology of Hirschsprung's disease.
Assuntos
Doença de Hirschsprung , Humanos , Lactente , Doença de Hirschsprung/genética , Doença de Hirschsprung/metabolismo , Colo/metabolismo , Gânglios/metabolismo , Fibras Nervosas , Nervos Periféricos/metabolismoRESUMO
Traumatic optic neuropathy or other neurodegenerative diseases, including optic nerve transection, glaucoma, and diabetic retinopathy, can lead to progressive and irreversible visual damage. Long non-coding RNAs (lncRNAs), which belong to the family of non-protein-coding transcripts, have been linked to the pathogenesis, progression, and prognosis of these lesions. Retinal ganglion cells (RGCs) are critical for the transmission of visual information to the brain, damage to which results in visual loss. Apoptosis has been identified as one of the most essential modes of RGC death. Emerging evidence suggests that lncRNAs can regulate RGC degeneration by directly or indirectly modulating apoptosis-associated signaling pathways. This review presents a comprehensive overview of the role of lncRNAs in RGC apoptosis at transcriptional, post-transcriptional, translational, and post-translational levels, emphasizing on the potential mechanisms of action. The current limitations and future perspectives of exploring the connection between lncRNAs and RGC apoptosis have been summarized. Understanding the intricate molecular interaction network of lncRNAs and RGC apoptosis will open new avenues for the identification of novel diagnostic biomarkers, therapeutic targets, and molecules for prognostic evaluation of diseases related to RGC injury.
Assuntos
Glaucoma , RNA Longo não Codificante , Humanos , Células Ganglionares da Retina/metabolismo , RNA Longo não Codificante/metabolismo , Apoptose/fisiologia , Gânglios/metabolismo , Glaucoma/metabolismo , Glaucoma/patologiaRESUMO
The diversity of visual input processed by the mammalian visual system requires the generation of many distinct retinal ganglion cell (RGC) types, each tuned to a particular feature. The molecular code needed to generate this cell-type diversity is poorly understood. Here, we focus on the molecules needed to specify one type of retinal cell: the upward-preferring ON direction-selective ganglion cell (up-oDSGC) of the mouse visual system. Single-cell transcriptomic profiling of up- and down-oDSGCs shows that the transcription factor Tbx5 is selectively expressed in up-oDSGCs. The loss of Tbx5 in up-oDSGCs results in a selective defect in the formation of up-oDSGCs and a corresponding inability to detect vertical motion. A downstream effector of Tbx5, Sfrp1, is also critical for vertical motion detection but not up-oDSGC formation. These results advance our understanding of the molecular mechanisms that specify a rare retinal cell type and show how disrupting this specification leads to a corresponding defect in neural circuitry and behavior.
Assuntos
Células Ganglionares da Retina , Fatores de Transcrição , Animais , Gânglios/metabolismo , Regulação da Expressão Gênica , Camundongos , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Proteínas com Domínio T , Fatores de Transcrição/metabolismoRESUMO
Studied by electron microscopy and morphometry, Auerbach's ganglia comprise nerve cell bodies that occupy ~ 40% of volume; of the neuropil, little over 30% is neural processes (axons, dendrites) and little less than 30% is glia (cell bodies, processes). The amount of surface membrane of neural elements only marginally exceeds that of glia. Glial cells extend laminar processes radially between axons, reaching the ganglion's surface with specialized membrane domains. Nerve cells and glia are tightly associated, eliminating any free space in ganglia. Glia expands maximally its cell membrane with a minimum of cytoplasm, contacting a maximal number of axons, which, with their near-circular profile, have minimal surface for a given volume. Shape of glia is moulded by the neural elements (predominantly concave the first, predominantly convex the second); the glia extends its processes to maximize contact with neural elements. Yet, a majority of axons is not reached by glia and only few are wrapped by it. Despite the large number of cells, the glia is not sufficiently developed to wrap around or just contact many of the neural elements. Mitochondria are markedly fewer in glia than in neurons, indicating a lower metabolic rate. Compactness of ganglia, their near-circular profile, absence of spaces between elements and ability to withstand extensive deformation suggest strong adhesion between the cellular elements, holding them together and keeping them at a fixed distance. Many axonal varicosities, with vesicles and membrane densities, abut on non-specialized areas of glia, suggesting the possibility of neurotransmitters being released outside synaptic sites.
Assuntos
Plexo Mientérico , Neuroglia , Animais , Axônios/metabolismo , Gânglios/metabolismo , Cobaias , Mitocôndrias , Plexo Mientérico/metabolismo , Neuroglia/metabolismoRESUMO
The nervous system expresses neuromolecules that play a crucial role in regulating physiological processes. Neuromolecule synthesis can be regulated by oxygen-dependent enzymes. Bivalves are a convenient model for studying air exposure-induced hypoxia. Here, we studied the effects of hypoxia on the expression and dynamics of neurotransmitters, and on neurotransmitter enzyme distribution, in the central nervous system (CNS) of the scallop Azumapecten farreri. We analyzed the expression of the neurotransmitters FMRFamide and serotonin (5-HT) and the choline acetyltransferase (CHAT) and universal NO-synthase (uNOS) enzymes during air exposure-induced hypoxia. We found that, in early-stage hypoxia, total serotonin content decreased in some CNS regions but increased in others. CHAT-lir cell numbers increased in all ganglia after hypoxia; CHAT probably appears de novo in accessory ganglia. Short-term hypoxia caused increased uNOS-lir cell numbers, while long-term exposure led to a reduction in their number. Thus, hypoxia weakly influences the number of FMRFamide-lir neurons in the visceral ganglion and does not affect peptide expression in the pedal ganglion. Ultimately, we found that the localization and level of synthesis of neuromolecules, and the numbers of cells expressing these molecules, vary in the scallop CNS during hypoxia exposure. This indicates their possible involvement in hypoxia resistance mechanisms.
Assuntos
Gânglios/metabolismo , Hipóxia/metabolismo , Neurotransmissores/metabolismo , Pectinidae/metabolismo , Transmissão Sináptica/fisiologia , Animais , Sistema Nervoso Central/metabolismo , Colina O-Acetiltransferase/metabolismo , FMRFamida/metabolismo , Neurônios/metabolismo , Serotonina/metabolismoRESUMO
The expression of 5-HT (serotonin) receptors (sr) was analyzed in the spinal cord and ganglia of 15 human conceptuses (5-10-weeks), and in the 9-week fetus with spina bifida. We used immunohistochemical method to detect sr-positive, apoptotic (caspase-3) and proliferating (Ki-67) cells, double immunofluorescence for co-localization with protein gene peptide (pgp) 9.5 and GFAP, as well as semiquantification and statistical measurements. Following the neurulation process, moderate (sr1 and sr2) and mild (sr3) expression characterized neuroblasts in the spinal cord and ganglia. During further development, sr1 expression gradually increased in the motoneurons, autonomic and sensory neurons, while sr2 and sr3 increased strongly in floor and roof plates. In the ganglia, sr3 expression increased during limited developmental period, while sr1 and sr2 increased throughout the investigated period. Co-expression of sr/pgp 9.5 characterized developing neurons, while sr/GFAP co-localized in the roof plate. In the spinal cord and ganglia of malformed fetus, weaker sr1 and sr2 and stronger sr3 expression accompanied morphological abnormalities. Anomalous roof plate morphology showed an excess of apoptotic and proliferating cells and increased sr3 expression. Our results indicate a human-species specific sr expression pattern, and the importance of sr1 in neuronal differentiation, and sr2 and sr3 in the control of the roof plate morphogenesis in normal and disturbed development.
Assuntos
Feto/metabolismo , Gânglios Espinais/metabolismo , Gânglios/metabolismo , Receptores de Serotonina/metabolismo , Medula Espinal/metabolismo , Disrafismo Espinal/metabolismo , Apoptose/fisiologia , Caspase 3/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Antígeno Ki-67/metabolismo , Células Receptoras Sensoriais/metabolismo , Serotonina/metabolismoRESUMO
Neonicotinoid insecticides are nicotine-derived molecules which exert acute neurotoxic effects over the insect central nervous system by activating nicotinic acetylcholine receptors (nAChRs). However, these receptors are also present in the mammalian central and peripheral nervous system, where the effects of neonicotinoids are faintly known. In mammals, cholinergic synapses are crucial for the control of vascular tone, blood pressure and skeletal muscle contraction. We therefore hypothesized that neonicotinoids could affect cholinergic networks in mammals and sought to highlight functional consequences of acute intoxication in rats with sub-lethal concentrations of the highly used acetamiprid (ACE) and clothianidin (CLO). In this view, we characterized their electrophysiological effects on rat α3ß4 nAChRs, knowing that it is predominantly expressed in ganglia of the vegetative nervous system and the adrenal medulla, which initiates catecholamine secretion. Both molecules exhibited a weak agonist effect on α3ß4 receptors. Accordingly, their influence on epinephrine secretion from rat adrenal glands was also weak at 100 µM, but it was stronger at 500 µM. Challenging ACE or CLO together with nicotine (NIC) ended up with paradoxical effects on secretion. In addition, we measured the rat arterial blood pressure (ABP) in vivo by arterial catheterization. As expected, NIC induced a significant increase in ABP. ACE and CLO did not affect the ABP in the same conditions. However, simultaneous exposure of rats to both NIC and ACE/CLO promoted an increase of ABP and induced a biphasic response. Modeling the interaction of ACE or CLO on α3ß4 nAChR is consistent with a binding site located in the agonist pocket of the receptor. We present a transversal experimental approach of mammal intoxication with neonicotinoids at different scales, including in vitro, ex vivo, in vivo and in silico. It paves the way of the acute and chronic toxicity for this class of insecticides on mammalian organisms.
Assuntos
Epinefrina/metabolismo , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Nicotina/toxicidade , Receptores Nicotínicos/metabolismo , Medula Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/metabolismo , Animais , Pressão Arterial/efeitos dos fármacos , Modelos Animais de Doenças , Agonismo Parcial de Drogas , Gânglios/efeitos dos fármacos , Gânglios/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Guanidinas/toxicidade , Masculino , Ratos , Tiazóis/toxicidade , Testes de Toxicidade SubagudaRESUMO
Although first described over a hundred years ago, tissue optical clearing is undergoing renewed interest due to numerous advances in optical clearing methods, microscopy systems, and three-dimensional (3-D) image analysis programs. These advances are advantageous for intact mouse tissues or pieces of human tissues because samples sized several millimeters can be studied. Optical clearing methods are particularly useful for studies of the neuroanatomy of the central and peripheral nervous systems and tissue vasculature or lymphatic system. Using examples from solvent- and aqueous-based optical clearing methods, the mouse and human pancreatic structures and networks will be reviewed in 3-D for neuro-insular complexes, parasympathetic ganglia, and adipocyte infiltration as well as lymphatics in diabetes. Optical clearing with multiplex immunofluorescence microscopy provides new opportunities to examine the role of the nervous and circulatory systems in pancreatic and islet functions by defining their neurovascular anatomy in health and diabetes.
Assuntos
Imageamento Tridimensional/métodos , Pâncreas/diagnóstico por imagem , Adipócitos/patologia , Animais , Sistema Nervoso Autônomo/diagnóstico por imagem , Diabetes Mellitus/diagnóstico por imagem , Diabetes Mellitus/patologia , Gânglios/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Técnicas In Vitro , Ilhotas Pancreáticas/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Neuroanatomia , Pâncreas/irrigação sanguínea , Células de Schwann/patologiaRESUMO
BACKGROUND: Recent studies reported metabolic uptake in at least one of the evaluated ganglia in 98.5% of patients undergoing 68Ga -PSMA-11 and in 96.9% of patients undergoing 18F-DCFPyL PET/CT examination. We have observed different patterns of ganglion visualization with 18F-DCFPyL compared to 68Ga-PSMA-11. This includes more frequent visualization of cervical and sacral ganglia, which may be attributable to better imaging characteristics with 18F PET imaging. CASE PRESENTATION: This pictorial essay is to illustrate and compare, in the same patient, various representative cases of 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia at different anatomic locations, with different patterns and distribution of metabolic activity. CONCLUSION: Reading physicians should be aware of the frequently encountered and occasionally different physiologic uptake of 68Ga-PSMA-11 and 18F DCFPyL in different ganglia.
Assuntos
Ácido Edético/análogos & derivados , Gânglios/metabolismo , Oligopeptídeos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/fisiopatologia , Ácido Edético/metabolismo , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , MasculinoRESUMO
The MAPK pathway is a major growth signal that has been implicated during the development of progenitors, neurons, and glia in the embryonic brain. Here, we show that the MAPK pathway plays an important role in the generation of distinct cell types from progenitors in the ventral telencephalon. Our data reveal that phospho-p44/42 (called p-ERK1/2) and the ETS transcription factor Etv5, both downstream effectors in the MAPK pathway, show a regional bias in expression during ventral telencephalic development, with enriched expression in the dorsal region of the LGE and ventral region of the MGE at E13.5 and E15.5. Interestingly, expression of both factors becomes more uniform in ventricular zone (VZ) progenitors by E18.5. To gain insight into the role of MAPK activity during progenitor cell development, we used a cre inducible constitutively active MEK1 allele (RosaMEK1DD/+) in combination with a ventral telencephalon enriched cre (Gsx2e-cre) or a dorsal telencephalon enriched cre (Emx1cre/+). Sustained MEK/MAPK activity in the ventral telencephalon (Gsx2e-cre; RosaMEK1DD/+) expanded dorsal lateral ganglionic eminence (dLGE) enriched genes (Gsx2 and Sp8) and oligodendrocyte progenitor cell (OPC) markers (Olig2, Pdgfrα, and Sox10), and also reduced markers in the ventral (v) LGE domain (Isl1 and Foxp1). Activation of MEK/MAPK activity in the dorsal telencephalon (Emx1cre/+; RosaMEK1DD/+) did not initially activate the expression of dLGE or OPC genes at E15.5 but ectopic expression of Gsx2 and OPC markers were observed at E18.5. These results support the idea that MAPK activity as readout by p-ERK1/2 and Etv5 expression is enriched in distinct subdomains of ventral telencephalic progenitors during development. In addition, sustained activation of the MEK/MAPK pathway in the ventral or dorsal telencephalon influences dLGE and OPC identity from progenitors.
Assuntos
Diferenciação Celular/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Telencéfalo/metabolismo , Animais , Proteínas de Ligação a DNA/metabolismo , Embrião de Mamíferos/metabolismo , Gânglios/metabolismo , Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Homeodomínio/metabolismo , MAP Quinase Quinase 1/metabolismo , Camundongos , Camundongos Transgênicos , Células-Tronco Neurais/citologia , Neurogênese/fisiologia , Neuroglia/metabolismo , Neurônios/metabolismo , Fatores de Transcrição SOXE/genética , Telencéfalo/embriologia , Telencéfalo/fisiologia , Fatores de Transcrição/metabolismoRESUMO
In vertebrates, gonadotropin-releasing hormone (GnRH) regulates gonadal maturation by stimulating the synthesis and release of pituitary gonadotropins. GnRH has also been identified in invertebrates. Crustacea consists of several classes including Cephalocarida, Remipedia, Branchiopoda (e.g., tadpole shrimp), Hexanauplia (e.g., barnacle) and Malacostraca (e.g., shrimp, crab). In the malacostracan crustaceans, the presence of GnRH has been detected in several species, mainly by immunohistochemistry. In the present study, we examined whether a GnRH-like peptide exists in the brain and/or nerve ganglion of three classes of crustaceans, the tadpole shrimp Triops longicaudatus (Branchiopoda), the barnacle Balanus crenatus (Hexanauplia), and the hermit crab Pagurus filholi (Malacostraca), by immunohistochemistry using a rabbit polyclonal antibody raised against chicken GnRH-II (GnRH2). This antibody was found to recognize the giant freshwater prawn Macrobrachium rosenbergii GnRH (MroGnRH). In the tadpole shrimp, GnRH-like-immunoreactive (ir) cell bodies were located in the circumesophageal connective of the deuterocerebrum, and GnRH-like-ir fibers were detected also in the ventral nerve cord. In the barnacle, GnRH-like-ir cell bodies and fibers were located in the supraesophageal ganglion (brain), the subesophageal ganglion, and the circumesophageal connective. In the hermit crab, GnRH-like-ir cell bodies were detected in the anterior-most part of the supraesophageal ganglion and the subesophageal ganglion. GnRH-like-ir fibers were observed also in the thoracic ganglion and the eyestalk. These results suggest that a GnRH-like peptide exists widely in crustacean species.
Assuntos
Crustáceos/anatomia & histologia , Crustáceos/metabolismo , Gânglios/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Animais , Imuno-Histoquímica , Peptídeos/análiseRESUMO
A 74-year-old man with a history of prostate cancer with proven osseous metastatic disease underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT under antiandrogen therapy. The scan revealed a long segment of increased PSMA tracer uptake within the right sciatic nerve, which appeared edematous and swollen, and the respective ganglia. Clinically, the patient suffered from pain and paresis in the right leg. As infiltration of a long segment of a single nerve seems unlikely, primarily neuronal disease such as neuritis (induced by metastases or radiotherapy) was considered. The observed uptake of PSMA-targeting PET tracers may then represent a peripheral nerve disorder.
Assuntos
Ácido Edético/análogos & derivados , Gânglios/metabolismo , Nervos Periféricos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Transporte Biológico , Neoplasias Ósseas/secundário , Ácido Edético/metabolismo , Gânglios/diagnóstico por imagem , Gânglios/patologia , Humanos , Masculino , Nervos Periféricos/diagnóstico por imagem , Nervos Periféricos/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
Plexitis in the proximal margin of intestinal resections are associated with post-operative recurrence of Crohn's disease. To understand their formation, in vitro analyzes were performed. T cells adhered preferentially to neuron and glial cells in mixed primary cultures of enteric nervous system and T cell activation increased their adhesion capacity. Higher number of T lymphocytes in close proximity to enteric glial cells was also observed in the myenteric ganglia of Crohn's patients as compared to control. These data show that close proximity between lymphocytes and enteric neural cells exists and may contribute to the formation of plexitis.
Assuntos
Adesão Celular/fisiologia , Doença de Crohn/metabolismo , Gânglios/metabolismo , Plexo Mientérico/metabolismo , Neurônios/metabolismo , Linfócitos T/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Doença de Crohn/patologia , Sistema Nervoso Entérico/metabolismo , Sistema Nervoso Entérico/patologia , Feminino , Gânglios/patologia , Humanos , Plexo Mientérico/patologia , Neurônios/patologia , Gravidez , Ratos , Ratos Sprague-Dawley , Linfócitos T/patologiaRESUMO
S-nitroso-l-cysteine (L-CSNO) behaves as a ligand. Its soluble guanylate cyclase-independent (sGC-independent) effects are stereoselective - that is, not recapitulated by S-nitroso-d-cysteine (D-CSNO) - and are inhibited by chemical congeners. However, candidate L-CSNO receptors have not been identified. Here, we have used 2 complementary affinity chromatography assays - followed by unbiased proteomic analysis - to identify voltage-gated K+ channel (Kv) proteins as binding partners for L-CSNO. Stereoselective L-CSNO-Kv interaction was confirmed structurally and functionally using surface plasmon resonance spectroscopy; hydrogen deuterium exchange; and, in Kv1.1/Kv1.2/Kvß2-overexpressing cells, patch clamp assays. Remarkably, these sGC-independent L-CSNO effects did not involve S-nitrosylation of Kv proteins. In isolated rat and mouse respiratory control (petrosyl) ganglia, L-CSNO stereoselectively inhibited Kv channel function. Genetic ablation of Kv1.1 prevented this effect. In intact animals, L-CSNO injection at the level of the carotid body dramatically and stereoselectively increased minute ventilation while having no effect on blood pressure; this effect was inhibited by the L-CSNO congener S-methyl-l-cysteine. Kv proteins are physiologically relevant targets of endogenous L-CSNO. This may be a signaling pathway of broad relevance.
Assuntos
Cisteína/análogos & derivados , Gânglios/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Proteoma/metabolismo , S-Nitrosotióis/metabolismo , Animais , Cisteína/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , EstereoisomerismoRESUMO
Intestinal ischemia/reperfusion (I/R) injury has severe consequences on myenteric neurons, which can be irreversibly compromised resulting in slowing of transit and hindered food digestion. Myenteric neurons synthesize hyaluronan (HA) to form a well-structured perineuronal net, which undergoes derangement when myenteric ganglia homeostasis is perturbed, i.e. during inflammation. In this study we evaluated HA involvement in rat small intestine myenteric plexus after in vivo I/R injury induced by clamping a branch of the superior mesenteric artery for 60 min, followed by 24 h of reperfusion. In some experiments, 4-methylumbelliferone (4-MU, 25 mg/kg), a HA synthesis inhibitor, was intraperitoneally administered to normal (CTR), sham-operated (SH) and I/R animals for 24 h. In longitudinal muscle myenteric plexus (LMMP) whole-mount preparations, HA binding protein staining as well as HA levels were significantly higher in the I/R group, and were reduced after 4-MU treatment. HA synthase 1 and 2 (HAS1 and HAS2) labelled myenteric neurons and mRNA levels in LMMPs increased in the I/R group with respect to CTR, and were reduced by 4-MU. The efficiency of the gastrointestinal transit was significantly reduced in I/R and 4-MU-treated I/R groups with respect to CTR and SH groups. In the 4-MU-treated I/R group gastric emptying was reduced with respect to the CTR, SH and I/R groups. Carbachol (CCh) and electrical field (EFS, 0.1-40 Hz) stimulated contractions and EFS-induced (10 Hz) NANC relaxations were reduced in the I/R group with respect to both CTR and SH groups. After I/R, 4-MU treatment increased EFS contractions towards control values, but did not affect CCh-induced contractions. NANC on-relaxations after I/R were not influenced by 4-MU treatment. Main alterations in the neurochemical coding of both excitatory (tachykinergic) and inhibitory pathways (iNOS, VIPergic) were also observed after I/R, and were influenced by 4-MU administration. Overall, our data suggest that, after an intestinal I/R damage, changes of HA homeostasis in specific myenteric neuron populations may influence the efficiency of the gastrointestinal transit. We cannot exclude that modulation of HA synthesis in these conditions may ameliorate derangement of the enteric motor function preventing, at least in part, the development of dysmotility.
Assuntos
Trânsito Gastrointestinal/fisiologia , Ácido Hialurônico/metabolismo , Intestino Delgado/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Modelos Animais de Doenças , Gânglios/metabolismo , Motilidade Gastrointestinal/genética , Motilidade Gastrointestinal/fisiologia , Trânsito Gastrointestinal/genética , Humanos , Hialuronan Sintases/genética , Íleo/metabolismo , Íleo/fisiologia , Intestino Delgado/patologia , Plexo Mientérico/metabolismo , Fenômenos Fisiológicos do Sistema Nervoso , Neurônios/metabolismo , Neurônios/patologia , Ratos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologiaRESUMO
The jugular ganglion (JG) contains sensory neurons of the vagus nerve which innervate somatic and visceral structures in cranial and cervical regions. In this study, the number of sensory neurons in the human JG was investigated. And, the morphology of sensory neurons in the human JG and nodose ganglion (NG) was compared. The estimated number of JG neurons was 2721.8-9301.1 (average number of sensory neurons⯱â¯S.D.â¯=â¯7975.1⯱â¯3312.8). There was no significant difference in sizes of the neuronal cell body and nucleus within the JG (cell body, 1128.8⯱â¯99.7 µâ¯m2; nucleus, 127.7⯱â¯20.8 µâ¯m2) and NG (cell body, 963.8⯱â¯225.7 µâ¯m2; nucleus, 123.2⯱â¯32.3 µâ¯m2). These findings indicate that most of sensory neurons show the similar morphology in the JG and NG. Our immunohistochemical method also demonstrated the distribution of ion channels, neurotransmitter agents and calcium-binding proteins in the human JG. Numerous JG neurons were immunoreactive for transient receptor potential cation channel subfamily V member 1 (TRPV1, mean⯱â¯SDâ¯=â¯19.9⯱â¯11.5 %) and calcitonin gene-related peptide (CGRP, 28.4⯱â¯6.7 %). A moderate number of JG neurons contained TRPV2 (12.0⯱â¯4.7 %), substance P (SP, 15.7⯱â¯6.9 %) and secreted protein, acidic and rich in cysteine-like 1 (SPARCL1, 14.6⯱â¯7.4 %). A few JG neurons had vesicular glutamate transporter 2 (VGLUT2, 5.6⯱â¯2.9 %) and parvalbumin (PV, 2.3⯱â¯1.4 %). SP- and TRPV2-containing JG neurons had mainly small and medium-sized cell bodies, respectively. TRPV1- and VGLUT2- containing JG neurons were small to medium-sized. CGRP- and SPARCL1-containing JG neurons were of various cell body sizes. Sensory neurons in the human JG were mostly free of vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH) and neuropeptide Y (NPY). In the external auditory canal skin, subepithelial nerve fibers contained TRPV1, TRPV2, SP, CGRP and VGLUT2. Perivascular nerve fibers also had TRPV1, TRPV2, SP, CGRP, VIP, NPY and TH. However, PV- and SPARCL1-containing nerve endings could not be seen in the external auditory canal. It is likely that sensory neurons in the human JG can transduce nociceptive and mechanoreceptive information from the external auditory canal. Theses neurons may be also associated with neurogenic inflammation in the external auditory canal and ear-cough reflex through the vagus nerve.