In vivo survival and differentiation of Friedreich ataxia iPSC ‐derived sensory neurons transplanted in the adult dorsal root ganglia

Background Inflammation of the dorsal root ganglia (DRG) may contribute to low back pain, postherpetic neuralgia, and neuropathic pain. The mineralocorticoid receptor (MR) plays a proinflammatory role in many nonrenal tissues, but its role in peripheral pain at the DRG level is not well studied. Methods Local inflammation of the L5 DRG with the immune activator zymosan rapidly leads to mechanical hypersensitivity and increased excitability of sensory neurons. Using this pain model, the authors applied the MR antagonist eplerenone locally to the inflamed DRG. Excitability of small-diameter sensory neurons was examined in acute primary culture by using patch clamp techniques. Results Local eplerenone significantly reduced the mechanical hypersensitivity and shortened its duration. The same dose was ineffective systemically. Immunohistochemical studies showed the MR was present in most neurons and rapidly translocated to the nucleus 1 day after local DRG inflammation. Activation of satellite glia (defined by expression of glial fibrillary acidic protein) in the inflamed DRG was also reduced by local eplerenone. Increased excitability of small-diameter sensory neurons 1 day after inflammation could be observed in vitro. Eplerenone applied in vitro (8-12 h) could reverse this increased excitability. Eplerenone had no effect in neurons isolated from normal, uninflamed DRG. The MR agonist aldosterone (10 nM) applied in vitro increased excitability of neurons isolated from normal DRG. Conclusions The MR may have a pronociceptive role in the DRG. Some of its effects may be mediated by neuronal MR. The MR may represent a novel therapeutic target in some pain syndromes.

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

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200117110056 ◽

2020 ◽

Vol 19 (1) ◽

pp. 66-82 ◽

Cited By ~ 2

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.

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

Neuroscience ◽

10.1016/j.neuroscience.2009.03.087 ◽

2009 ◽

Vol 161 (3) ◽

pp. 838-846 ◽

Cited By ~ 33

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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M2-Receptor Subtype Does Not Mediate Muscarine-Induced Increases in [Ca2+]i in Nociceptive Neurons of Rat Dorsal Root Ganglia

Journal of Neurophysiology ◽

10.1152/jn.2000.84.4.1934 ◽

2000 ◽

Vol 84 (4) ◽

pp. 1934-1941 ◽

Cited By ~ 21

Author(s):

Rainer Haberberger ◽

Reas Scholz ◽

Wolfgang Kummer ◽

Michaela Kress

Keyword(s):

Receptor Antagonist ◽

Muscarinic Receptor ◽

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Receptor Subtype ◽

Receptor Subtypes ◽

Muscarinic Receptor Subtypes ◽

Rt Pcr ◽

Nociceptive Neurons

Multiple muscarinic receptor subtypes are present on sensory neurons that may be involved in the modulation of nociception. In this study we focused on the presence of the muscarinic receptor subtypes, M2 and M3 (M2R, M3R), in adult rat lumbar dorsal root ganglia (DRG) at the functional ([Ca2+]i measurement), transcriptional (RT-PCR), and translational level (immunohistochemistry). After 1 day in culture exposure of dissociated medium-sized neurons (20–35 μm diam) to muscarine was followed by rises in [Ca2+]i in 76% of the neurons. The [Ca2+]i increase was absent after removal of extracellular calcium and did not desensitize after repetitive application of the agonist. This rise in [Ca2+]i may be explained by the expression of M3R, which can induce release of calcium from internal stores via inositoltrisphospate. Indeed the effect was antagonized by the muscarinic receptor antagonist atropine as well as by the M3R antagonist, 4-diphenylacetoxy-N-(2 chloroethyl)-piperidine hydrochloride (4-DAMP). The pharmacological identification of M3R was corroborated by RT-PCR of total RNA and single-cell RT-PCR, which revealed the presence of mRNA for M3R in lumbar DRG and in single sensory neurons. In addition, RT-PCR also revealed the expression of M2R, which did not seem to contribute to the calcium changes since it was not prevented by the M2 receptor antagonist, gallamine. Immunohistochemistry demonstrated the presence of M2R and M3R in medium-sized lumbar DRG neurons that also coexpressed binding sites for the lectin I-B4, a marker for mainly cutaneous nociceptors. The occurrence of muscarinic receptors in putative nociceptive I-B4-positive neurons suggests the involvement of these acetylcholine receptors in the modulation of processing of nociceptive stimuli.

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Purinergic signaling between neurons and satellite glial cells of mouse dorsal root ganglia modulates neuronal excitability in vivo

Pain ◽

10.1097/j.pain.0000000000002556 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Zhiyong Chen ◽

Qian Huang ◽

Xiaodan Song ◽

Neil C. Ford ◽

Chi Zhang ◽

...

Keyword(s):

Glial Cells ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Neuronal Excitability ◽

Purinergic Signaling ◽

Satellite Glial Cells

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Frataxin gene editing rescues Friedreich’s ataxia pathology in dorsal root ganglia organoid-derived sensory neurons

Nature Communications ◽

10.1038/s41467-020-17954-3 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Pietro Giuseppe Mazzara ◽

Sharon Muggeo ◽

Mirko Luoni ◽

Luca Massimino ◽

Mattia Zaghi ◽

...

Keyword(s):

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Gene Editing ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Frataxin Gene

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RNA-Binding Proteins HuB, HuC, and HuD are Distinctly Regulated in Dorsal Root Ganglia Neurons from STZ-Sensitive Compared to STZ-Resistant Diabetic Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20081965 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1965 ◽

Cited By ~ 1

Author(s):

Cosmin Cătălin Mustăciosu ◽

Adela Banciu ◽

Călin Mircea Rusu ◽

Daniel Dumitru Banciu ◽

Diana Savu ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Transcriptional Control ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Diabetic Mice

The neuron-specific Elav-like Hu RNA-binding proteins were described to play an important role in neuronal differentiation and plasticity by ensuring the post-transcriptional control of RNAs encoding for various proteins. Although Elav-like Hu proteins alterations were reported in diabetes or neuropathy, little is known about the regulation of neuron-specific Elav-like Hu RNA-binding proteins in sensory neurons of dorsal root ganglia (DRG) due to the diabetic condition. The goal of our study was to analyze the gene and protein expression of HuB, HuC, and HuD in DRG sensory neurons in diabetes. The diabetic condition was induced in CD-1 adult male mice with single-intraperitoneal injection of streptozotocin (STZ, 150 mg/kg), and 8-weeks (advanced diabetes) after induction was quantified the Elav-like proteins expression. Based on the glycemia values, we identified two types of responses to STZ, and mice were classified in STZ-resistant (diabetic resistant, glycemia < 260 mg/dL) and STZ-sensitive (diabetic, glycemia > 260 mg/dL). Body weight measurements indicated that 8-weeks after STZ-induction of diabetes, control mice have a higher increase in body weight compared to the diabetic and diabetic resistant mice. Moreover, after 8-weeks, diabetic mice (19.52 ± 3.52 s) have longer paw withdrawal latencies in the hot-plate test than diabetic resistant (11.36 ± 1.92 s) and control (11.03 ± 1.97 s) mice, that correlates with the installation of warm hypoalgesia due to the diabetic condition. Further on, we evidenced the decrease of Elav-like gene expression in DRG neurons of diabetic mice (Elavl2, 0.68 ± 0.05 fold; Elavl3, 0.65 ± 0.01 fold; Elavl4, 0.53 ± 0.07 fold) and diabetic resistant mice (Ealvl2, 0.56 ± 0.07 fold; Elavl3, 0.32 ± 0.09 fold) compared to control mice. Interestingly, Elav-like genes have a more accentuated downregulation in diabetic resistant than in diabetic mice, although hypoalgesia was evidenced only in diabetic mice. The Elav-like gene expression changes do not always correlate with the Hu protein expression changes. To detail, HuB is upregulated and HuD is downregulated in diabetic mice, while HuB, HuC, and HuD are downregulated in diabetic resistant mice compared to control mice. To resume, we demonstrated HuD downregulation and HuB upregulation in DRG sensory neurons induced by diabetes, which might be correlated with altered post-transcriptional control of RNAs involved in the regulation of thermal hypoalgesia condition caused by the advanced diabetic neuropathy.

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Isolation and Culture of Sensory Neurons From the Dorsal-Root Ganglia of Embryonic or Adult Rats

Pain Research - Methods in Molecular Medicine ◽

10.1385/1-59259-770-x:055 ◽

2004 ◽

pp. 189-202 ◽

Cited By ~ 8

Author(s):

Thomas H. Burkey ◽

Cynthia M. Hingtgen ◽

Michael R. Vasko

Keyword(s):

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Adult Rats

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

Journal of Food Protection ◽

10.4315/0362-028x-71.11.2307 ◽

2008 ◽

Vol 71 (11) ◽

pp. 2307-2311 ◽

Cited By ~ 1

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.

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