scholarly journals Innate Receptors Expression by Lung Nociceptors: Impact on COVID-19 and Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos H. Hiroki ◽  
Nicole Sarden ◽  
Mortaza F. Hassanabad ◽  
Bryan G. Yipp
Keyword(s):  
Sensory Neurons ◽  
Tissue Injury ◽  
Sensory Nerve ◽  
Immunological Responses ◽  
Pathogen Invasion ◽  
Neuron Activation ◽  
New Findings ◽  
Pulmonary Immunity ◽  
External Stimuli ◽  
Efficient Mechanisms

The lungs are constantly exposed to non-sterile air which carries harmful threats, such as particles and pathogens. Nonetheless, this organ is equipped with fast and efficient mechanisms to eliminate these threats from the airways as well as prevent pathogen invasion. The respiratory tract is densely innervated by sensory neurons, also known as nociceptors, which are responsible for the detection of external stimuli and initiation of physiological and immunological responses. Furthermore, expression of functional innate receptors by nociceptors have been reported; however, the influence of these receptors to the lung function and local immune response is poorly described. The COVID-19 pandemic has shown the importance of coordinated and competent pulmonary immunity for the prevention of pathogen spread as well as prevention of excessive tissue injury. New findings suggest that lung nociceptors can be a target of SARS-CoV-2 infection; what remains unclear is whether innate receptor trigger sensory neuron activation during SARS-CoV-2 infection and what is the relevance for the outcomes. Moreover, elderly individuals often present with respiratory, neurological and immunological dysfunction. Whether aging in the context of sensory nerve function and innate receptors contributes to the disorders of these systems is currently unknown. Here we discuss the expression of innate receptors by nociceptors, particularly in the lungs, and the possible impact of their activation on pulmonary immunity. We then demonstrate recent evidence that suggests lung sensory neurons as reservoirs for SARS-CoV-2 and possible viral recognition via innate receptors. Lastly, we explore the mechanisms by which lung nociceptors might contribute to disturbance in respiratory and immunological responses during the aging process.

scholarly journals Imaging sensory transmission and neuronal plasticity in primary sensory neurons with genetically-encoded voltage indicators

2021 ◽  
Author(s):  
Yan Zhang ◽  
John Shannonhouse ◽  
Ruben Gomez ◽  
Hyeonwi Son ◽  
Hirotake Ishida ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Dynamic Range ◽  
Temporal Dynamics ◽  
Tissue Injury ◽  
Spatiotemporal Analysis ◽  
Primary Sensory Neurons ◽  
Simultaneous Imaging ◽  
Integration Mechanisms ◽  
External Stimuli

Detection of somatosensory inputs requires conversion of external stimuli into electrical signals by activation of primary sensory neurons. The mechanisms by which heterogeneous primary sensory neurons encode different somatosensory inputs remains unclear. In vivo dorsal root ganglia (DRG) imaging using genetically-encoded Ca2+ indicators (GECIs) is currently the best technique for this purpose by providing an unprecedented spatial and populational resolution. It permits the simultaneous imaging of >1800 neurons/DRG in live mice. However, this approach is not ideal given that Ca2+ is a second messenger and has inherently slow response kinetics. In contrast, genetically-encoded voltage indicators (GEVIs) have the potential to track voltage changes in multiple neurons in real time but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4, a novel GEVI, to dissect the temporal dynamics of noxious and non-noxious neuronal signals during mechanical, thermal, or chemical stimulation in DRG of live mice. ASAP4 is sufficiently bright and fast enough to optically characterize individual neuron coding dynamics. Notably, using ASAP4, we uncovered cell-to-cell electrical synchronization between adjacent DRG neurons and robust dynamic transformations in sensory coding following tissue injury. Finally, we found that a combination of GEVI and GECI imaging empowered in vivo optical studies of sensory signal processing and integration mechanisms with optimal spatiotemporal analysis.

scholarly journals Imaging sensory transmission and neuronal plasticity in primary sensory neurons with a positively tuned voltage indicator

2021 ◽  
Author(s):  
Yu Shin Kim ◽  
Yan Zhang ◽  
John Shannonhouse ◽  
Ruben Gomez ◽  
Hyeonwi Son ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Dynamic Range ◽  
Temporal Dynamics ◽  
Tissue Injury ◽  
Spatiotemporal Analysis ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Integration Mechanisms ◽  
External Stimuli

Abstract Detection of somatosensory inputs requires conversion of external stimuli into electrical signals by activation of primary sensory neurons. The mechanisms by which heterogeneous primary sensory neurons encode different somatosensory inputs remains unclear. In vivo dorsal root ganglia (DRG) imaging using genetically-encoded Ca2+ indicators (GECIs) is currently the best technique for this purpose mapping neuronal function in DRG circuits by providing an unprecedented spatial and populational resolution. It permits the simultaneous imaging of >1800 neurons/DRG in live mice. However, this approach is not ideal given that Ca2+ is a second messenger and has inherently slow response kinetics. In contrast, genetically-encoded voltage indicators (GEVIs) have the potential to track voltage changes in multiple neurons in real time but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4.4-Kv, a novel positively tuned GEVI, to dissect the temporal dynamics of noxious and non-noxious neuronal signals during mechanical, thermal, or chemical stimulation in DRG neurons of live mice. ASAP4.4-Kv is sufficiently bright and fast enough to optically characterize individual neuron coding dynamics. Notably, using ASAP4.4-Kv, we uncovered cell-to-cell electrical synchronization between adjacent DRG neurons and robust dynamic transformations in sensory coding following tissue injury. Finally, we found that a combination of GEVI and GECI imaging empowered in vivo optical studies of sensory signal processing and integration mechanisms with optimal spatiotemporal analysis.

scholarly journals Voltage-gated Na+ currents in human dorsal root ganglion neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Xiulin Zhang ◽  
Birgit T Priest ◽  
Inna Belfer ◽  
Michael S Gold
Keyword(s):  
Sensory Neurons ◽  
Tissue Injury ◽  
Dorsal Root Ganglion Neurons ◽  
Pharmacological Properties ◽  
Pain Mechanisms ◽  
Voltage Gated ◽  
Whole Cell Patch Clamp ◽  
Na Currents ◽  
Ganglion Neurons ◽  
Peripheral Sensory

Available evidence indicates voltage-gated Na+ channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp techniques were used to study Na+ currents in acutely dissociated neurons from human and rat. Our results indicate that while the two major current types, generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were qualitatively similar in neurons from rats and humans, there were several differences that have important implications for drug development as well as our understanding of pain mechanisms.

scholarly journals Roles of Toll-Like Receptors in Nitroxidative Stress in Mammals

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 576 ◽  
Author(s):  
Yao Li ◽  
Shou-Long Deng ◽  
Zheng-Xing Lian ◽  
Kun Yu
Keyword(s):  
Membrane Lipids ◽  
Tissue Injury ◽  
Reactive Oxygen ◽  
Innate Immune ◽  
Cellular Damage ◽  
Inflammatory Factors ◽  
Nitrogen Species ◽  
Toll Like Receptors ◽  
Pathogen Invasion ◽  
Microbial Products

Free radicals are important antimicrobial effectors that cause damage to DNA, membrane lipids, and proteins. Professional phagocytes produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute towards the destruction of pathogens. Toll-like receptors (TLRs) play a fundamental role in the innate immune response and respond to conserved microbial products and endogenous molecules resulting from cellular damage to elicit an effective defense against invading pathogens, tissue injury, or cancer. In recent years, several studies have focused on how the TLR-mediated activation of innate immune cells leads to the production of pro-inflammatory factors upon pathogen invasion. Here, we review recent findings that indicate that TLRs trigger a signaling cascade that induces the production of reactive oxygen and nitrogen species.

Sensory Control and Organization of Neural Networks Mediating Coordination of Multisegmental Organs for Locomotion

2005 ◽  
Vol 93 (3) ◽  
pp. 1127-1135 ◽  
Author(s):  
Ansgar Büschges
Keyword(s):  
Neural Networks ◽  
Nervous System ◽  
Sensory Neurons ◽  
Sensory Feedback ◽  
Stick Insect ◽  
Sensory Control ◽  
Recent Advances ◽  
New Findings ◽  
Local Feedback ◽  
Locomotor Patterns

It is well established that locomotor patterns result from the interaction between central pattern generating networks in the nervous system, local feedback from sensory neurons about movements and forces generated in the locomotor organs, and coordinating signals from neighboring segments or appendages. This review addresses the issue of how the movements of multi-segmented locomotor organs are coordinated and provides an overview of recent advances in understanding sensory control and the internal organization of central pattern generating networks that operate multi-segmented locomotor organs, such as a walking leg. Findings from the stick insect and the cat are compared and discussed in relation to new findings on the lamprey swimming network. These findings support the notion that common schemes of sensory feedback are used for generating walking and that central neural networks controlling multi-segmented locomotor organs generally encompass multiple central pattern generating networks that correspond with the segmental structure of the locomotor organ.

scholarly journals A RasGRP, C. elegans RGEF-1b, Couples External Stimuli to Behavior by Activating LET-60 (Ras) in Sensory Neurons

Neuron ◽  
2011 ◽  
Vol 70 (1) ◽  
pp. 51-65 ◽  
Author(s):  
Lu Chen ◽  
Ya Fu ◽  
Min Ren ◽  
Bing Xiao ◽  
Charles S. Rubin
Keyword(s):  
Sensory Neurons ◽  
C Elegans ◽  
External Stimuli

scholarly journals Activation of Porcine Alveolar Macrophages byActinobacillus pleuropneumoniaeLipopolysaccharide via the Toll-Like Receptor 4/NF-κB-Mediated Pathway

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Bi Li ◽  
Jing Fang ◽  
Zhicai Zuo ◽  
Sirui Yin ◽  
Tingting He ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Alveolar Macrophages ◽  
Intracellular Signaling ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Immunological Responses ◽  
Pathogen Invasion ◽  
Porcine Contagious Pleuropneumonia

ABSTRACTActinobacillus pleuropneumoniaeis the causative agent of porcine contagious pleuropneumonia. Overproduction of proinflammatory cytokines, like interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and resistin, in the lung is an important feature ofA. pleuropneumoniaeinfection. These proinflammatory cytokines enhance inflammatory and immunological responses. However, the mechanism that leads to cytokine production remains unclear. As a major virulence factor ofA. pleuropneumoniae, lipopolysaccharide (LPS) may act as a potent stimulator of Toll-like receptor 4 (TLR4), triggering a number of intracellular signaling pathways that lead to the synthesis of proinflammatory cytokines. Porcine alveolar macrophages (PAMs) are the first line of defense against pathogenic microbes during pathogen invasion. The results of the present study demonstrate thatA. pleuropneumoniaeLPS induces PAMs to produce inflammatory cytokines in time- and dose-dependent manners. Moreover, PAMs were activated byA. pleuropneumoniaeLPS, resulting in upregulation of signaling molecules, including TLR4, MyD88, TRIF-related adaptor molecule, and NF-κB. In contrast, the activation effects ofA. pleuropneumoniaeLPS on PAMs could be suppressed by specific inhibitors, like small interfering RNA and Bay11-7082. Taken together, our data indicate thatA. pleuropneumoniaeLPS can induce PAMs to produce proinflammatory cytokines via the TLR4/NF-κB-mediated pathway. These findings partially reveal the mechanism of the overproduction of proinflammatory cytokines in the lungs of swine withA. pleuropneumoniaeinfection and may provide targets for the prevention ofA. pleuropneumoniae-induced pneumonia. All the data could be used as a reference for the pathogenesis of respiratory infection.

II. Integration of afferent signaling from the viscera by the nodose ganglia

2003 ◽  
Vol 284 (1) ◽  
pp. G8-G14 ◽  
Author(s):  
Kirsteen N. Browning ◽  
David Mendelowitz
Keyword(s):  
Sensory Neurons ◽  
Tissue Injury ◽  
Large Body ◽  
Sensory Function ◽  
Afferent Neurons ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
Afferent Signaling ◽  
Recent Demonstration ◽  
Stimulation Of

To understand vago-vagal reflexes, one must have an appreciation of the events surrounding the encoding, integration, and central transfer of peripheral sensations by vagal afferent neurons. A large body of work has shown that vagal afferent neurons have nonuniform properties and that distinct subpopulations of neurons exist within the nodose ganglia. These sensory neurons display a considerable degree of plasticity; electrophysiological, pharmacological, and neurochemical properties have all been shown to alter after peripheral tissue injury. The validity of claims of selective recordings from populations of neurons activated by peripheral stimuli may be diminished, however, by the recent demonstration that stimulation of a subpopulation of nodose neurons can enhance the activity of unstimulated neuronal neighbors. To better understand the neurophysiological processes occurring after vagal afferent stimulation, it is essential that the electrophysiological, pharmacological, and neurochemical properties of nodose neurons are correlated with their sensory function or, at the very least, with their specific innervation target.

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