RESUMO
Taste information is encoded in the gustatory nervous system much as in other sensory systems, with notable exceptions. The concept of adequate stimulus is common to all sensory modalities, from somatosensory to auditory, visual, and so forth. That is, sensory cells normally respond only to one particular form of stimulation, the adequate stimulus, such as photons (photoreceptors in the visual system), odors (olfactory sensory neurons in the olfactory system), noxious heat (nociceptors in the somatosensory system), etc. Peripheral sensory receptors transduce the stimulus into membrane potential changes transmitted to the brain in the form of trains of action potentials. How information concerning different aspects of the stimulus such as quality, intensity, and duration are encoded in the trains of action potentials is hotly debated in the field of taste. At one extreme is the notion of labeled line/spatial coding - information for each different taste quality (sweet, salty, sour, etc.) is transmitted along a parallel but separate series of neurons (a "line") that project to focal clusters ("spaces") of neurons in the gustatory cortex. These clusters are distinct for each taste quality. Opposing this are concepts of population/combinatorial coding and temporal coding, where taste information is encrypted by groups of neurons (circuits) and patterns of impulses within these neuronal circuits. Key to population/combinatorial and temporal coding is that impulse activity in an individual neuron does not provide unambiguous information about the taste stimulus. Only populations of neurons and their impulse firing pattern yield that information.
Assuntos
Células Receptoras Sensoriais , Paladar , Potenciais de Ação/fisiologia , Humanos , Percepção , Paladar/fisiologiaRESUMO
BACKGROUND: Eya2 expression during mouse development has been studied by in situ hybridization and it has been shown to be involved skeletal muscle development and limb formation. Here, we generated Eya2 knockout (Eya2- ) and a lacZ knockin reporter (Eya2lacZ ) mice and performed a detailed expression analysis for Eya2lacZ at different developmental stages to trace Eya2lacZ -positive cells in Eya2-null mice. We describe that Eya2 is not only expressed in cranial sensory and dorsal root ganglia, retina and olfactory epithelium, and somites as previously reported, but also Eya2 is specifically detected in other organs during mouse development. RESULTS: We found that Eya2 is expressed in ocular and trochlear motor neurons. In the inner ear, Eya2lacZ is specifically expressed in differentiating hair cells in both vestibular and cochlear sensory epithelia of the inner ear and Eya2-/- or Eya2lacZ/lacZ mice displayed mild hearing loss. Furthermore, we detected Eya2 expression during both salivary gland and thymus development and Eya2-null mice had a smaller thymus. CONCLUSIONS: As Eya2 is coexpressed with other members of the Eya family genes, these results together highlight that Eya2 as a potential regulator may act synergistically with other Eya genes to regulate the differentiation of the inner ear sensory hair cells and the formation of the salivary gland and thymus.
Assuntos
Orelha Interna/metabolismo , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Perda Auditiva/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Animais , Diferenciação Celular/fisiologia , Orelha Interna/embriologia , Perda Auditiva/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas Nucleares/genética , Proteínas Tirosina Fosfatases/genéticaRESUMO
Astroglia are neural cells, heterogeneous in form and function, which act as supportive elements of the central nervous system; astrocytes contribute to all aspects of neural functions in health and disease. Through their highly ramified processes, astrocytes form close physical contacts with synapses and blood vessels, and are integrated into functional syncytia by gap junctions. Astrocytes interact among themselves and with other cells types (e.g., neurons, microglia, blood vessel cells) by an elaborate repertoire of chemical messengers and receptors; astrocytes also influence neural plasticity and synaptic transmission through maintaining homeostasis of neurotransmitters, K+ buffering, synaptic isolation and control over synaptogenesis and synaptic elimination. Satellite glial cells (SGCs) are the most abundant glial cells in sensory ganglia, and are believed to play major roles in sensory functions, but so far research into SGCs attracted relatively little attention. In this review we compare SGCs to astrocytes with the purpose of using the vast knowledge on astrocytes to explore new aspects of SGCs. We survey the main properties of these two cells types and highlight similarities and differences between them. We conclude that despite the much greater diversity in morphology and signaling mechanisms of astrocytes, there are some parallels between them and SGCs. Both types serve as boundary cells, separating different compartments in the nervous system, but much more needs to be learned on this aspect of SGCs. Astrocytes and SGCs employ chemical messengers and calcium waves for intercellular signaling, but their significance is still poorly understood for both cell types. Both types undergo major changes under pathological conditions, which have a protective function, but an also contribute to disease, and chronic pain in particular. The knowledge obtained on astrocytes is likely to benefit future research on SGCs.
Assuntos
Astrócitos/classificação , Astrócitos/fisiologia , Animais , Astrócitos/citologia , Astrócitos/patologia , Sinalização do Cálcio/fisiologia , Extensões da Superfície Celular/fisiologia , Junções Comunicantes/fisiologia , Humanos , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/fisiopatologiaRESUMO
In vertebrates, cranial placodes contribute to all sense organs and sensory ganglia and arise from a common pool of Six1/Eya2+ progenitors. Here we dissect the events that specify ectodermal cells as placode progenitors using newly identified genes upstream of the Six/Eya complex. We show in chick that two different tissues, namely the lateral head mesoderm and the prechordal mesendoderm, gradually induce placode progenitors: cells pass through successive transcriptional states, each identified by distinct factors and controlled by different signals. Both tissues initiate a common transcriptional state but over time impart regional character, with the acquisition of anterior identity dependent on Shh signalling. Using a network inference approach we predict the regulatory relationships among newly identified transcription factors and verify predicted links in knockdown experiments. Based on this analysis we propose a new model for placode progenitor induction, in which the initial induction of a generic transcriptional state precedes regional divergence.
Assuntos
Transdução de Sinais/fisiologia , Vertebrados/embriologia , Animais , Comunicação Celular/genética , Comunicação Celular/fisiologia , Embrião de Galinha , Galinhas , Ectoderma/citologia , Ectoderma/embriologia , Ectoderma/metabolismo , Eletroporação , Gânglios Sensitivos/citologia , Gânglios Sensitivos/embriologia , Gânglios Sensitivos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hibridização In Situ , Análise de Sequência com Séries de Oligonucleotídeos , Codorniz , Órgãos dos Sentidos/citologia , Órgãos dos Sentidos/embriologia , Órgãos dos Sentidos/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Vertebrados/metabolismoRESUMO
Some chronic pain conditions in the orofacial region are common, the mechanisms underlying which are unresolved. Satellite glial cells (SGCs) are the glial cells of the peripheral nervous system. In the sensory ganglia, each neuronal body is surrounded by SGCs forming distinct functional units. The unique structural organization enables SGCs to communicate with each other and with their enwrapped neurons via a variety of ways. There is a growing body of evidence that SGCs can influence the level of neuronal excitability and are involved in the development and/or maintenance of pain. The aim of this review was to summarize the latest advances made about the implication of SGCs in orofacial pain. It may offer new targets for the development of orofacial pain treatment.
Assuntos
Comunicação Celular/fisiologia , Dor Facial/metabolismo , Neuralgia/metabolismo , Neuroglia/fisiologia , Células Satélites Perineuronais/metabolismo , Gânglios Sensitivos/metabolismo , Humanos , Neuroglia/metabolismo , Neurônios/fisiologia , Gânglio Trigeminal/fisiologia , Nervo TrigêmeoRESUMO
We compared apparent origins, cellular diversity and regulation of initial axon growth for differentiating cranial sensory neurons. We assessed the molecular and cellular composition of the developing olfactory and otic placodes, and cranial sensory ganglia to evaluate contributions of ectodermal placode versus neural crest at each site. Special sensory neuron populations-the olfactory and otic placodes, as well as those in vestibulo-acoustic ganglion- are entirely populated with cells expressing cranial placode-associated, rather than neural crest-associated markers. The remaining cranial sensory ganglia are a mosaic of cells that express placode-associated as well as neural crest-associated markers. We found two distinct populations of neural crest in the cranial ganglia: the first, as expected, is labeled by Wnt1:Cre mediated recombination. The second is not labeled by Wnt1:Cre recombination, and expresses both Sox10 and FoxD3. These populations-Wnt1:Cre recombined, and Sox10/Foxd3-expressing- are proliferatively distinct from one another. Together, the two neural crest-associated populations are substantially more proliferative than their placode-associated counterparts. Nevertheless, the apparently placode- and neural crest-associated populations are similarly sensitive to altered signaling that compromises cranial morphogenesis and differentiation. Acute disruption of either Fibroblast growth factor (Fgf) or Retinoic acid (RA) signaling alters axon growth and cell death, but does not preferentially target any of the three distinct populations. Apparently, mosaic derivation and diversity of precursors and early differentiating neurons, modulated uniformly by local signals, supports early cranial sensory neuron differentiation and growth.
Assuntos
Nervos Cranianos/citologia , Células Receptoras Sensoriais/citologia , Animais , Apoptose , Axônios/fisiologia , Diferenciação Celular , Linhagem da Célula , Nervos Cranianos/embriologia , Ectoderma/citologia , Fatores de Crescimento de Fibroblastos/fisiologia , Gânglios Sensitivos/citologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas Luminescentes/análise , Proteínas Luminescentes/genética , Camundongos , Camundongos Endogâmicos C57BL , Crista Neural/citologia , Neurogênese , Fatores de Transcrição/genética , Tretinoína/fisiologia , Proteína Wnt1/fisiologiaRESUMO
Varicella zoster virus (VZV) causes varicella during acute infection and establishes latency in the sensory ganglia. Reactivation of VZV results in herpes zoster, a debilitating and painful disease. It is believed that VZV reactivates due to a decline in cell-mediated immunity; however, the roles that CD4 versus CD8 T cells play in the prevention of herpes zoster remain poorly understood. To address this question, we used a well-characterized model of VZV infection where rhesus macaques are intrabronchially infected with the homologous simian varicella virus (SVV). Latently infected rhesus macaques were thymectomized and depleted of either CD4 or CD8 T cells to induce selective senescence of each T cell subset. After T cell depletion, the animals were transferred to a new housing room to induce stress. SVV reactivation (viremia in the absence of rash) was detected in three out of six CD8-depleted and two out of six CD4-depleted animals suggesting that both CD4 and CD8 T cells play a critical role in preventing SVV reactivation. Viral loads in multiple ganglia were higher in reactivated animals compared to non-reactivated animals. In addition, reactivation results in sustained transcriptional changes in the ganglia that enriched to gene ontology and diseases terms associated with neuronal function and inflammation indicative of potential damage as a result of viral reactivation. These studies support the critical role of cellular immunity in preventing varicella virus reactivation and indicate that reactivation results in long-lasting remodeling of the ganglia transcriptome.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Gânglios Sensitivos/imunologia , Herpes Zoster/veterinária , Herpesvirus Humano 3/imunologia , Proteínas do Tecido Nervoso/genética , Ativação Viral/imunologia , Animais , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Feminino , Gânglios Sensitivos/virologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Herpes Zoster/genética , Herpes Zoster/imunologia , Depleção Linfocítica/métodos , Macaca mulatta , Masculino , Anotação de Sequência Molecular , Proteínas do Tecido Nervoso/imunologia , Estresse Psicológico , Timectomia , Timo/imunologia , Timo/cirurgia , Timo/virologiaRESUMO
The main aim of the present review is to provide at first a short survey of the basic anatomical description of sensory ganglion neurons in relation to cell size, conduction velocity, thickness of myelin sheath, and functional classification of their processes. In addition, we have focused on discussing current knowledge about the distribution pattern of neuronal nitric oxide synthase containing sensory neurons especially in the dorsal root ganglia in different animal species; hence, there is a large controversy in relation to interpretation of the results dealing with this interesting field of research.
Assuntos
Gânglios Espinais/citologia , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Amielínicas/metabolismo , Neurônios Aferentes/enzimologia , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Gânglios Espinais/anatomia & histologia , Fibras Nervosas Mielinizadas/classificação , Fibras Nervosas Amielínicas/classificação , Neurônios Aferentes/classificação , Neurônios Aferentes/fisiologia , Substância P/metabolismoRESUMO
The majority of cranial sensory neurons originate in placodes in the surface ectoderm, migrating to form ganglia that connect to the central nervous system (CNS). Interactions between inward-migrating sensory neuroblasts and emigrant cranial neural crest cells (NCCs) play a role in coordinating this process, but how the relationship between these two cell populations is established is not clear. Here, we demonstrate that NCCs generate corridors delineating the path of migratory neuroblasts between the placode and CNS in both chick and mouse. In vitro analysis shows that NCCs are not essential for neuroblast migration, yet act as a superior substrate to mesoderm, suggesting provision of a corridor through a less-permissive mesodermal territory. Early organisation of NCC corridors occurs prior to sensory neurogenesis and can be recapitulated in vitro; however, NCC extension to the placode requires placodal neurogenesis, demonstrating reciprocal interactions. Together, our data indicate that NCC corridors impose physical organisation for precise ganglion formation and connection to the CNS, providing a local environment to enclose migrating neuroblasts and axonal processes as they migrate through a non-neural territory.
Assuntos
Movimento Celular/fisiologia , Gânglios Sensitivos/embriologia , Crista Neural/fisiologia , Células-Tronco Neurais/fisiologia , Células Receptoras Sensoriais/fisiologia , Crânio/embriologia , Animais , Embrião de Galinha , Gânglios Sensitivos/citologia , Hibridização In Situ , Camundongos , Microscopia Confocal , Crânio/citologiaRESUMO
Herpes simplex virus type 1 (HSV-1) initiates productive infection in mucocutaneous tissues to cause cold sores and establishes latent infection in the trigeminal ganglia. Under certain circumstances, HSV-1 may cause encephalitis. Here, we compared host innate defenses against HSV-1 in the two clinically relevant tissues, skin and brain, using a unique ex vivo system of organ culture. Upon HSV-1 infection and spread, apoptosis induction was observed in the skin, but not in brain tissues. While the two tissues elicited interferon (IFN-ß) response upon HSV1 infection, IFN induction was more robust in the skin compared to the brain. Moreover, antiviral response to exogenous IFNß treatment was much stronger in the skin compared to brain tissues. This observation was not related to the availability of the IFN receptor on cells' surface. Taken together, our study demonstrates differential innate antiviral responses to HSV-1 infection that may be exploited in future development of selective and tissue-specific anti-viral treatments.
Assuntos
Encéfalo/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Pele/imunologia , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/imunologia , Herpes Simples/genética , Herpes Simples/patologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/crescimento & desenvolvimento , Humanos , Interferon beta/farmacologia , Óperon Lac , Camundongos , Proteínas de Resistência a Myxovirus/genética , Proteínas de Resistência a Myxovirus/imunologia , Técnicas de Cultura de Órgãos , Especificidade de Órgãos , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/imunologia , Pele/efeitos dos fármacos , Pele/patologia , Replicação Viral/efeitos dos fármacosRESUMO
Primary simian varicella virus (SVV) infection in non-human primates causes varicella, after which the virus becomes latent in ganglionic neurons and reactivates to cause zoster. The host response in ganglia during establishment of latency is ill-defined. Ganglia from five African green monkeys (AGMs) obtained at 9, 13, and 20 days post-intratracheal SVV inoculation (dpi) were analyzed by ex vivo flow cytometry, immunohistochemistry, and in situ hybridization. Ganglia at 13 and 20 dpi exhibited mild inflammation. Immune infiltrates consisted mostly of CD8(dim) and CD8(bright) memory T cells, some of which expressed granzyme B, and fewer CD11c(+) and CD68(+) cells. Chemoattractant CXCL10 transcripts were expressed in neurons and infiltrating inflammatory cells but did not co-localize with SVV open reading frame 63 (ORF63) RNA expression. Satellite glial cells expressed increased levels of activation markers CD68 and MHC class II at 13 and 20 dpi compared to those at 9 dpi. Overall, local immune responses emerged as viral DNA load in ganglia declined, suggesting that intra-ganglionic immunity contributes to restricting SVV replication.
Assuntos
Gânglios Sensitivos/imunologia , Herpesvirus Humano 3/imunologia , Doenças dos Primatas/imunologia , Células Receptoras Sensoriais/imunologia , Infecção pelo Vírus da Varicela-Zoster/veterinária , Ativação Viral , Latência Viral , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígeno CD11c/genética , Antígeno CD11c/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Chlorocebus aethiops , DNA Viral/genética , DNA Viral/imunologia , Gânglios Sensitivos/virologia , Regulação da Expressão Gênica/imunologia , Granzimas/genética , Granzimas/imunologia , Herpesvirus Humano 3/patogenicidade , Interações Hospedeiro-Patógeno , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/imunologia , Memória Imunológica , Doenças dos Primatas/genética , Doenças dos Primatas/patologia , Células Receptoras Sensoriais/virologia , Infecção pelo Vírus da Varicela-Zoster/genética , Infecção pelo Vírus da Varicela-Zoster/imunologia , Infecção pelo Vírus da Varicela-Zoster/patologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Carga Viral/genética , Carga Viral/imunologiaRESUMO
Axonal branching is a prerequisite for the establishment of complex neuronal circuits and their capacity for parallel information processing. Previously, we have identified a cGMP signaling pathway composed of the ligand C-type natriuretic peptide (CNP), its receptor, the guanylyl cyclase natriuretic peptide receptor 2 (Npr2), and the cGMP-dependent kinase Iα (cGKIα) that regulates axon bifurcation of dorsal root ganglion (DRG) neurons in the spinal cord. Now we asked whether this cascade also controls axon bifurcation elsewhere in the nervous system. An Npr2-lacZ reporter mouse line was generated to clarify the pattern of the CNP receptor expression. It was found that during the period of axonal outgrowth, Npr2 and cGKIα were strongly labeled in neurons of all cranial sensory ganglia (gV, gVII, gVIII, gIX, and gX). In addition, strong complementary expression of CNP was detected in the hindbrain at the entry zones of sensory afferents. To analyze axon branching in individual Npr2-positive neurons, we generated a mouse mutant expressing a tamoxifen-inducible variant of Cre recombinase expressed under control of the Npr2-promoter (Npr2-CreER(T2)). After crossing this strain with conditional reporter mouse lines, we revealed that the complete absence of Npr2 activity indeed prohibited the bifurcation of cranial sensory axons in their entrance region. Consequently, axons only turned in either an ascending or descending direction, while collateral formation and growth of the peripheral arm was not affected. These findings indicate that in neurons of the cranial sensory ganglia, as in DRG neurons, cGMP signals are necessary for the execution of an axonal bifurcation program.
Assuntos
Axônios/química , Nervos Cranianos/química , GMP Cíclico/genética , Receptores do Fator Natriurético Atrial/deficiência , Células Receptoras Sensoriais/química , Transdução de Sinais/genética , Animais , Axônios/fisiologia , Nervos Cranianos/patologia , Nervos Cranianos/fisiologia , GMP Cíclico/fisiologia , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/patologia , Células-Tronco Embrionárias/fisiologia , Feminino , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Camundongos Transgênicos , Receptores do Fator Natriurético Atrial/genética , Receptores do Fator Natriurético Atrial/fisiologia , Células Receptoras Sensoriais/patologiaRESUMO
The dysfunction of the ubiquitin proteasome system has been related to a broad array of neurodegenerative disorders in which the accumulation of misfolded protein aggregates causes proteotoxicity. The ability of proteasome inhibitors to induce cell cycle arrest and apoptosis has emerged as a powerful strategy for cancer therapy. Bortezomib is a proteasome inhibitor used as an antineoplastic drug, although its neurotoxicity frequently causes a severe sensory peripheral neuropathy. In this study we used a rat model of bortezomib treatment to study the nucleolar and Cajal body responses to the proteasome inhibition in sensory ganglion neurons that are major targets of bortezomib-induced neurotoxicity. Treatment with bortezomib induced dose-dependent dissociation of protein synthesis machinery (chromatolysis) and nuclear retention of poly(A) RNA granules resulting in neuronal dysfunction. However, as a compensatory response to the proteotoxic stress, both nucleoli and Cajal bodies exhibited reactive changes. These include an increase in the number and size of nucleoli, strong nucleolar incorporation of the RNA precursor 5'-fluorouridine, and increased expression of both 45S rRNA and genes encoding nucleolar proteins UBF, fibrillarin and B23. Taken together, these findings appear to reflect the activation of the nucleolar transcription in response to proteotoxic stress Furthermore, the number of Cajal bodies, a parameter related to transcriptional activity, increases upon proteasome inhibition. We propose that nucleoli and Cajal bodies are important targets in the signaling pathways that are activated by the proteotoxic stress response to proteasome inhibition. The coordinating activity of these two organelles in the production of snRNA, snoRNA and rRNA may contribute to neuronal survival after proteasome inhibition. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
Assuntos
Corpos Enovelados/metabolismo , Gânglios Sensitivos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Células Receptoras Sensoriais/metabolismo , Animais , Ácidos Borônicos/administração & dosagem , Bortezomib , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Nucléolo Celular/metabolismo , Núcleo Celular , Citoplasma/metabolismo , Gânglios Sensitivos/crescimento & desenvolvimento , Humanos , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Pirazinas/administração & dosagem , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
Aquaporin-4 (AQP4) is a water channel protein that is predominantly expressed in astrocytes in the CNS. The rapid water flux through AQP4 may contribute to electrolyte/water homeostasis and may support neuronal activities in the CNS. On the other hand, little is known about the expression of AQP4 in the peripheral nervous system (PNS). Using AQP4(-/-) mice as a negative control, we demonstrated that AQP4 is also expressed in sensory ganglia, such as trigeminal ganglia and dorsal root ganglia in the PNS. Immunohistochemistry revealed that AQP4 is exclusively localized to satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in the sensory ganglia. Biochemical analyses revealed that the expression levels of AQP4 in sensory ganglia were considerably lower than those in astrocytes in the CNS. Consistently, behavioral analyses did not show any significant difference in terms of mechanical and cold sensitivity between wild type and AQP4(-/-) mice. Overall, although the pathophysiological relevance of AQP4 in somatosensory perception remains unclear, our findings provide new insight into the involvement of water homeostasis in the peripheral sensory system.
Assuntos
Aquaporina 4/biossíntese , Gânglios Sensitivos/metabolismo , Animais , Astrócitos/metabolismo , Temperatura Baixa , Homeostase , Camundongos , Neuroglia/metabolismo , Água/metabolismoRESUMO
Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons. An increasing body of evidence suggests that in the presence of inflammation and nerve damage, a significant number of satellite glial cells become activated, thus triggering a series of functional changes. This suggests that satellite glial cells are closely related to the occurrence of chronic pain. In this review, we first summarize the morphological structure, molecular markers, and physiological functions of satellite glial cells. Then, we clarify the multiple key roles of satellite glial cells in chronic pain, including gap junction hemichannel Cx43, membrane channel Pannexin1, K channel subunit 4.1, ATP, purinergic P2 receptors, and a series of additional factors and their receptors, including tumor necrosis factor, glutamate, endothelin, and bradykinin. Finally, we propose that future research should focus on the specific sorting of satellite glial cells, and identify genomic differences between physiological and pathological conditions. This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.
RESUMO
The sympathetic ganglia represent a final motor pathway that mediates homeostatic "fight and flight" responses in the visceral organs. Satellite glial cells (SGCs) form a thin envelope close to the neuronal cell body and synapses in the sympathetic ganglia. This unique morphological feature suggests that neurons and SGCs form functional units for regulation of sympathetic output. In the present study, we addressed whether SGC-specific markers undergo age-dependent changes in the postnatal development of rat sympathetic ganglia. We found that fatty acid-binding protein 7 (FABP7) is an early SGC marker, whereas the S100B calcium-binding protein, inwardly rectifying potassium channel, Kir4.1 and small conductance calcium-activated potassium channel, SK3 are late SGC markers in the postnatal development of sympathetic ganglia. Unlike in sensory ganglia, FABP7 + SGC was barely detectable in adult sympathetic ganglia. The expression of connexin 43, a gap junction channel gradually increased with age, although it was detected in both SGCs and neurons in sympathetic ganglia. Glutamine synthetase was expressed in sensory, but not sympathetic SGCs. Unexpectedly, the sympathetic SGCs expressed a water-selective channel, aquaporin 1 instead of aquaporin 4, a pan-glial marker. However, aquaporin 1 was not detected in the SGCs encircling large neurons. Nerve injury and inflammation induced the upregulation of glial fibrillary acidic protein, suggesting that this protein is a hall marker of glial activation in the sympathetic ganglia. In conclusion, our findings provide basic information on the in vivo profiles of specific markers for identifying sympathetic SGCs at different stages of postnatal development in both healthy and diseased states.
Assuntos
Neuroglia , Células Satélites Perineuronais , Ratos , Animais , Células Satélites Perineuronais/metabolismo , Neuroglia/metabolismo , Gânglios Simpáticos , Neurônios , Proteína 7 de Ligação a Ácidos Graxos/metabolismo , Gânglios Espinais/metabolismoRESUMO
Reactive oxygen species (ROS) are generated in nociceptive pathways in response to inflammation and injury. ROS are accumulated within the sensory ganglia following peripheral inflammation, but the functional role of intraganlionic ROS in inflammatory pain is not clearly understood. The aims of this study were to investigate whether peripheral inflammation leads to prolonged ROS accumulation within the trigeminal ganglia (TG), whether intraganglionic ROS mediate pain hypersensitivity via activation of TRPA1, and whether TRPA1 expression is upregulated in TG during inflammatory conditions by ROS. We demonstrated that peripheral inflammation causes excess ROS production within TG during the period when inflammatory mechanical hyperalgesia is most prominent. Additionally, scavenging intraganglionic ROS attenuated inflammatory mechanical hyperalgesia and a pharmacological blockade of TRPA1 localized within TG also mitigated inflammatory mechanical hyperalgesia. Interestingly, exogenous administration of ROS into TG elicited mechanical hyperalgesia and spontaneous pain-like responses via TRPA1, and intraganglionic ROS induced TRPA1 upregulation in TG. These results collectively suggest that ROS accumulation in TG during peripheral inflammation contributes to pain and hyperalgesia in a TRPA1 dependent manner, and that ROS further exacerbate pathological pain responses by upregulating TRPA1 expression. Therefore, any conditions that exacerbate ROS accumulation within somatic sensory ganglia can aggravate pain responses and treatments reducing ganglionic ROS may help alleviate inflammatory pain.
RESUMO
Here we describe a novel neuro-mesodermal assembloid model that recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC) induction, migration, and sensory as well as sympathetic ganglion formation. The ganglia send projections to the mesodermal as well as neural compartment. Axons in the mesodermal part are associated with Schwann cells. In addition, peripheral ganglia and nerve fibers interact with a co-developing vascular plexus, forming a neurovascular niche. Finally, developing sensory ganglia show response to capsaicin indicating their functionality. The presented assembloid model could help to uncover mechanisms of human NCC induction, delamination, migration, and PNS development. Moreover, the model could be used for toxicity screenings or drug testing. The co-development of mesodermal and neuroectodermal tissues and a vascular plexus along with a PNS allows us to investigate the crosstalk between neuroectoderm and mesoderm and between peripheral neurons/neuroblasts and endothelial cells.
Assuntos
Células Endoteliais , Células-Tronco Neurais , Humanos , Células de Schwann , Axônios , Mesoderma , Crista Neural/fisiologiaRESUMO
Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.
Assuntos
Gânglios Sensitivos/metabolismo , Gânglios Espinais/metabolismo , Neuroglia/metabolismo , Células de Schwann/metabolismo , Animais , Gânglios Simpáticos/metabolismo , Humanos , Camundongos , Neurônios/metabolismo , Neurônios Aferentes , Sistema Nervoso Periférico/metabolismoRESUMO
Injury or inflammation in the peripheral branches of neurons of sensory ganglia causes changes in neuronal properties, including excessive firing, which may underlie chronic pain. The main types of glial cell in these ganglia are satellite glial cells (SGCs), which completely surround neuronal somata. SGCs undergo activation following peripheral lesions, which can enhance neuronal firing. How neuronal injury induces SGC activation has been an open question. Moreover, the mechanisms by which the injury is signaled from the periphery to the ganglia are obscure and may include electrical conduction, axonal and humoral transport, and transmission at the spinal level. We found that peripheral inflammation induced SGC activation and that the messenger between injured neurons and SGCs was nitric oxide (NO), acting by elevating cyclic guanosine monophosphate (cGMP) in SGCs. These results, together with work from other laboratories, indicate that a plausible (but not exclusive) mechanism for neuron-SGCs interactions can be formulated as follows: Firing due to peripheral injury induces NO formation in neuronal somata, which diffuses to SGCs. This stimulates cGMP synthesis in SGCs, leading to their activation and to other changes, which contribute to neuronal hyperexcitability and pain. Other mediators such as proinflammatory cytokines probably also contribute to neuron-SGC communications.