scholarly journals Activation of a nerve injury transcriptional signature in airway-innervating sensory neurons after LPS induced lung inflammation

2019 ◽  
Author(s):  
Melanie Maya Kaelberer ◽  
Ana Isabel Caceres ◽  
Sven-Eric Jordt
Keyword(s):  
Nerve Injury ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Lung Inflammation ◽  
Dorsal Root ◽  
The Other ◽  
Sensory Ganglia ◽  
Functional Changes ◽  
Transcriptional Signature ◽  
Nodose Ganglia

ABSTRACTThe lungs, the immune and nervous systems functionally interact to respond to respiratory environmental exposures and infections. The lungs are innervated by vagal sensory neurons of the jugular and nodose ganglia, fused together in smaller mammals as the jugular-nodose complex (JNC). While the JNC shares properties with the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG), these sensory structures express differential sets of genes that reflect their unique functionalities. Here, we used RNAseq in mice to identify the differential transcriptomes of the three sensory ganglia types. Using a fluorescent retrograde tracer and fluorescence-activated cell sorting we isolated a defined population of airway-innervating JNC neurons and determined their differential transcriptional map after pulmonary exposure to lipopolysaccharide (LPS), a major mediator of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after infection with Gram-negative bacteria or inhalation of organic dust. JNC neurons activated an injury response program leading to increased expression of gene products such as the G-protein coupled receptors, Cckbr, inducing functional changes in neuronal sensitivity to peptides, and Gpr151, also rapidly induced upon neuropathic nerve injury in pain models. Unique JNC-specific transcripts, present at only minimal levels in TG, DRG and other organs, were identified. These included TMC3, encoding for a putative mechanosensor, and Urotensin 2B, a hypertensive peptide. These findings highlight the unique properties of the JNC and reveal that ALI/ARDS rapidly induce a nerve-injury related state changing vagal excitability.SIGNIFICANCE STATEMENTThe lungs are innervated by sensory neurons of the jugular-nodose ganglia complex (JNC) that detect toxic exposures and interact with lung-resident cells and the immune system to respond to pathogens and inflammation. Here we report the expression of specific genes that differentiate these neurons from neurons in the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG). Through nerve tracing we identified and isolated airway innervating JNC neurons and determined their differential transcriptional map after lung inflammation induced by a bacterial product, lipopolysaccharide (LPS). We observed the rapid activation of a nerve injury transcriptional program that increased nerve sensitivity to inflammation. This mechanism may result in more permanent nerve injury associated with chronic cough and other respiratory complications.

scholarly journals Activation of a nerve injury transcriptional signature in airway-innervating sensory neurons after lipopolysaccharide-induced lung inflammation

2020 ◽  
Vol 318 (5) ◽  
pp. L953-L964 ◽  
Author(s):  
Melanie Maya Kaelberer ◽  
Ana Isabel Caceres ◽  
Sven-Eric Jordt
Keyword(s):  
Nerve Injury ◽  
Sensory Neurons ◽  
Sensory Ganglia ◽  
Functional Changes ◽  
Pulmonary Exposure ◽  
Transcriptional Signature ◽  
Nodose Ganglia ◽  
Pain Models ◽  
Sensory Structures ◽  
G Protein Coupled

The lungs and the immune and nervous systems functionally interact to respond to respiratory environmental exposures and infections. The lungs are innervated by vagal sensory neurons of the jugular and nodose ganglia, fused together in smaller mammals as the jugular-nodose complex (JNC). Whereas the JNC shares properties with the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG), these sensory structures express differential sets of genes that reflect their unique functionalities. Here, we used RNA sequencing (RNA-seq) in mice to identify the differential transcriptomes of the three sensory ganglia types. Using a fluorescent retrograde tracer and fluorescence-activated cell sorting, we isolated a defined population of airway-innervating JNC neurons and determined their differential transcriptional map after pulmonary exposure to lipopolysaccharide (LPS), a major mediator of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after infection with gram-negative bacteria or inhalation of organic dust. JNC neurons activated an injury response program, leading to increased expression of gene products such as the G protein-coupled receptor Cckbr, inducing functional changes in neuronal sensitivity to peptides, and Gpr151, also rapidly induced upon neuropathic nerve injury in pain models. Unique JNC-specific transcripts, present at only minimal levels in TG, DRG, and other organs, were identified. These included TMC3, encoding for a putative mechanosensor, and urotensin 2B, a hypertensive peptide. These findings highlight the unique properties of the JNC and reveal that ALI/ARDS rapidly induces a nerve injury-related state, changing vagal excitability.

An Evaluation of a Method for the Detection of Sensory Ganglia in Product Derived from Advanced Meat Recovery Systems†

2008 ◽  
Vol 71 (11) ◽  
pp. 2307-2311 ◽  
Author(s):  
SCOTT HAFNER ◽  
MARY T. SUTTON ◽  
JOSEPH HILL ◽  
PATRICK C. McCASKEY ◽  
LYNDA COLLINS KELLEY
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Single Cell ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Satellite Cells ◽  
Dorsal Root ◽  
Immunohistochemical Staining ◽  
Staining Pattern ◽  
Acidic Protein ◽  
Sensory Ganglia

A method is described for the identification of dorsal root ganglia (DRG)–associated sensory neurons within advanced meat recovery (AMR) product derived from bovine vertebral columns. This method relies on the unique microanatomy of sensory neurons and immunohistochemical staining, primarily for glial fibrillary acidic protein. Sensory neurons are variably sized unipolar neurons, exhibiting a single-cell process that is rarely seen in histologic sections. These neurons are surrounded by a prominent ring of glial fibrillary acidic protein–positive satellite cells that produce a distinctive and readily identifiable staining pattern in histologic sections. Fragmented DRG were detected to the 0.25% level in samples of ground beef or nonvertebral-origin AMR product spiked with these sensory ganglia. Similarly examined commercially produced nonvertebral-origin AMR product (n = 157) did not contain sensory ganglia, while 3.3% of vertebral-origin AMR product (n = 364) contained fragmented DRG.

BDNF-TrkB and proBDNF-p75NTR/Sortilin Signaling Pathways are Involved in Mitochondria-Mediated Neuronal Apoptosis in Dorsal Root Ganglia after Sciatic Nerve Transection

2020 ◽  
Vol 19 (1) ◽  
pp. 66-82 ◽  
Author(s):  
Xianbin Wang ◽  
Wei Ma ◽  
Tongtong Wang ◽  
Jinwei Yang ◽  
Zhen Wu ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Signaling Pathways ◽  
Nerve Injury ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neuronal Apoptosis ◽  
Nerve Transection ◽  
Sciatic Nerve Transection

Background: Brain-Derived Neurotrophic Factor (BDNF) plays critical roles during development of the central and peripheral nervous systems, as well as in neuronal survival after injury. Although proBDNF induces neuronal apoptosis after injury in vivo, whether it can also act as a death factor in vitro and in vivo under physiological conditions and after nerve injury, as well as its mechanism of inducing apoptosis, is still unclear. Objective: In this study, we investigated the mechanisms by which proBDNF causes apoptosis in sensory neurons and Satellite Glial Cells (SGCs) in Dorsal Root Ganglia (DRG) After Sciatic Nerve Transection (SNT). Methods: SGCs cultures were prepared and a scratch model was established to analyze the role of proBDNF in sensory neurons and SGCs in DRG following SNT. Following treatment with proBDNF antiserum, TUNEL and immunohistochemistry staining were used to detect the expression of Glial Fibrillary Acidic Protein (GFAP) and Calcitonin Gene-Related Peptide (CGRP) in DRG tissue; immunocytochemistry and Cell Counting Kit-8 (CCK8) assay were used to detect GFAP expression and cell viability of SGCs, respectively. RT-qPCR, western blot, and ELISA were used to measure mRNA and protein levels, respectively, of key factors in BDNF-TrkB, proBDNF-p75NTR/sortilin, and apoptosis signaling pathways. Results: proBDNF induced mitochondrial apoptosis of SGCs and neurons by modulating BDNF-TrkB and proBDNF-p75NTR/sortilin signaling pathways. In addition, neuroprotection was achieved by inhibiting the biological activity of endogenous proBDNF protein by injection of anti-proBDNF serum. Furthermore, the anti-proBDNF serum inhibited the activation of SGCs and promoted their proliferation. Conclusion: proBDNF induced apoptosis in SGCs and sensory neurons in DRG following SNT. The proBDNF signaling pathway is a potential novel therapeutic target for reducing sensory neuron and SGCs loss following peripheral nerve injury.

Painful Nerve Injury Decreases Resting Cytosolic Calcium Concentrations in Sensory Neurons of Rats

2005 ◽  
Vol 102 (6) ◽  
pp. 1217-1225 ◽  
Author(s):  
Andreas Fuchs ◽  
Philipp Lirk ◽  
Cheryl Stucky ◽  
Stephen E. Abram ◽  
Quinn H. Hogan
Keyword(s):  
Nerve Injury ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Sensory Information ◽  
Cytosolic Calcium ◽  
Skin Incision ◽  
Cellular Level ◽  
Spinal Nerve ◽  
Control Group

Background Neuropathic pain is difficult to treat and poorly understood at the cellular level. Although cytoplasmic calcium ([Ca]c) critically regulates neuronal function, the effects of peripheral nerve injury on resting sensory neuronal [Ca]c are unknown. Methods Resting [Ca]c was determined by microfluorometry in Fura-2 AM-loaded neurons dissociated from dorsal root ganglia of animals with hyperalgesia to mechanical stimulation after spinal nerve ligation and section (SNL) at the fifth and sixth lumbar (L5 and L6) levels and from animals after skin incision alone (control group). Axotomized neurons from the L5 dorsal root ganglia were examined separately from adjacent L4 neurons that share the sciatic nerve with degenerating L5 fibers. Results After SNL, large (34 mum or larger) neurons from the L4 ganglion showed a 29% decrease in resting [Ca]c, whereas those from the L5 ganglion showed a 54% decrease. Small neurons only showed an effect of injury in the axotomized L5 neurons, in which resting [Ca]c decreased by 30%. A decrease in resting [Ca]c was not seen in neurons isolated from rats in which hyperalgesia did not develop after SNL. In separate experiments, SNL reduced resting [Ca]c in capsaicin-insensitive neurons of the L5 ganglion by 60%, but there was no change in neurons from L4. Resting [Ca]c of capsaicin-sensitive neurons was not affected by injury in either ganglion. SNL injury decreased the proportion of neurons sensitive to capsaicin in the L5 group but increased the proportion in the L4 group. Conclusions Painful SNL nerve injury depresses resting [Ca]c in sensory neurons. This is most marked in axotomized neurons, especially the large and capsaicin-insensitive neurons presumed to transmit non-nociceptive sensory information.

scholarly journals Calcium Signaling in Intact Dorsal Root Ganglia

2010 ◽  
Vol 113 (1) ◽  
pp. 134-146 ◽  
Author(s):  
Geza Gemes ◽  
Marcel Rigaud ◽  
Andrew S. Koopmeiners ◽  
Mark J. Poroli ◽  
Vasiliki Zoga ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Field Stimulation ◽  
Fura 2 ◽  
High K ◽  
Neuronal Types ◽  
Potential Recording ◽  
Ca Signaling

Background Ca is the dominant second messenger in primary sensory neurons. In addition, disrupted Ca signaling is a prominent feature in pain models involving peripheral nerve injury. Standard cytoplasmic Ca recording techniques use high K or field stimulation and dissociated neurons. To compare findings in intact dorsal root ganglia, we used a method of simultaneous electrophysiologic and microfluorimetric recording. Methods Dissociated neurons were loaded by bath-applied Fura-2-AM and subjected to field stimulation. Alternatively, we adapted a technique in which neuronal somata of intact ganglia were loaded with Fura-2 through an intracellular microelectrode that provided simultaneous membrane potential recording during activation by action potentials (APs) conducted from attached dorsal roots. Results Field stimulation at levels necessary to activate neurons generated bath pH changes through electrolysis and failed to predictably drive neurons with AP trains. In the intact ganglion technique, single APs produced measurable Ca transients that were fourfold larger in presumed nociceptive C-type neurons than in nonnociceptive Abeta-type neurons. Unitary Ca transients summated during AP trains, forming transients with amplitudes that were highly dependent on stimulation frequency. Each neuron was tuned to a preferred frequency at which transient amplitude was maximal. Transients predominantly exhibited monoexponential recovery and had sustained plateaus during recovery only with trains of more than 100 APs. Nerve injury decreased Ca transients in C-type neurons, but increased transients in Abeta-type neurons. Conclusions Refined observation of Ca signaling is possible through natural activation by conducted APs in undissociated sensory neurons and reveals features distinct to neuronal types and injury state.

scholarly journals Autophagy of Sensory Neurons in the Trigeminal and Dorsal Root Ganglia of Cynomolgus Monkeys (Macaca fascicularis)

2019 ◽  
Vol 48 (1) ◽  
pp. 238-243 ◽  
Author(s):  
Mark Butt ◽  
Reina Fuji ◽  
Mike Reichelt ◽  
Alok K. Sharma ◽  
Sarah Cramer
Keyword(s):  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Macaca Fascicularis ◽  
Sensory Ganglia ◽  
Cynomolgus Monkeys ◽  
Distinct Cell ◽  
Small Group Size ◽  
Historical Control Data ◽  
Neuronal Autophagy

Although necrosis and apoptosis are uncommon, autophagy of sensory neurons (ASN) in trigeminal and dorsal root ganglia is a very common, spontaneous finding in cynomolgus monkeys ( Macaca fascicularis). Data from one author’s (Butt) laboratory showed 12 of 22 studies (year range 2017 to 2019) that included the evaluation of sensory ganglia from cynomolgus monkeys had at least one control animal with ASN. Autophagy of sensory neurons is characterized by a distinct cell membrane, cytoplasm filled with autolysosomes, disintegrated nuclear membrane, and/or globules of degraded chromatin. Since these changes are consistent with autophagy and indicate an irreversible state, a diagnosis of autophagy is preferred instead of necrosis or degeneration. Sensory ganglia are not commonly evaluated in nonclinical toxicology investigations so many pathologists may be unaware of this common change. Especially due to the typically small group size of monkey studies, the observation of this change in sensory ganglia may lead to a faulty interpretation that this change is due to the test article. This article describes the light microscopic and ultrastructural characteristics of neuronal autophagy in trigeminal and dorsal root ganglia and provides historical control data of the incidence of this change in cynomolgus monkeys.

The 5-HT2A receptor is mainly expressed in nociceptive sensory neurons in rat lumbar dorsal root ganglia

Neuroscience ◽  
2009 ◽  
Vol 161 (3) ◽  
pp. 838-846 ◽  
Author(s):  
J. Van Steenwinckel ◽  
A. Noghero ◽  
K. Thibault ◽  
M.-J. Brisorgueil ◽  
J. Fischer ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root
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