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Cross-section of a naive (A, B, C) and transected (D, E, F) Rana catesbeiana's dorsal root ganglion. A, Nuclear satellite glial cells (NSGC) with chromatin condensation and heterochromatin attached to the nuclear membrane. Note mitochondria (M) with an intracristal space of normal aspect. B and C, Ribosomes (R), rough endoplasmic reticulum (RER) and intermediate filaments (F) in the cytoplasm of satellite glial cell (SGC). Note the lamellar cytoplasmic expansion (Le) emerging from SGC. D, Nucleus of SGC of normal aspect 3 days after sciatic nerve transection. Note the greater number of M (D), RER (E) and F (F) in SGC cytoplasm. MC = tranverse mitochondrial cristae. Scale bars: A, B, C = 0.5 mm; E and F = 1 mm; D = 0.2 mm.
Source publication
Frogs have been used as an alternative model to study pain mechanisms. Since we did not find any reports on the effects of sciatic nerve transection (SNT) on the ultrastructure and pattern of metabolic substances in frog dorsal root ganglion (DRG) cells, in the present study, 18 adult male frogs (Rana catesbeiana) were divided into three experiment...
Contexts in source publication
Context 1
... nucleus of SGCs showed a characteristic chromatin condensation, with heterochromatin attached to the nuclear membrane. The nuclear envelope showed regular outlines and no changes were observed in its pores ( Figure 2D). A 10-12-nm thick plasma membrane was observed in SGCs and no interruptions along this membrane were seen. ...
Context 2
... 10-12-nm thick plasma membrane was observed in SGCs and no interruptions along this membrane were seen. Although no statistical analysis was performed, more ribosomes, RER, intermediate filaments, and mitochondria were observed in SGC cytoplasm ( Figure 2D-F). Many free ribosomes, polysomes, RER and mitochondria were evenly distributed throughout the SGC cytoplasm, while intermedi- ate filaments (8-10 nm in diameter) were more common in the perinuclear region, which seemed to form a very dense network. ...
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Background
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Citations
... Several subsequent Rambourg et al. (1983), outlining the characteristics of six types of dorsal root ganglion neurons (A1-3, B 1 and 2, C) based on ultrastructural features (see Table 1). The structure and localisation of the rough endoplasmic reticulum and Golgi apparatus were mainly used for differentiation between subtypes investigations have shown that individual DRG neurons of different species were normally completely surrounded by satellite cells (Cervos-Navarro 1959;Pannese 1960;Rigon et al. 2013;Ruiz-Soto et al. 2020). Scanning EM analysis showed that the neuron-satellite complexes in frogs and chickens have diameters of about 25 μm respectively (Matsuda et al. 2005). ...
... Transmission EM studies have shown that the thickness of the plasma membrane of satellite cells was 7-12 nm in rats and frogs and had many folds and borders. In addition, the neuronal cell body is separated from the satellite cells by a 10-12 nm wide intercellular space (Andres 1961a;Rigon et al. 2013). ...
Dorsal root ganglia (DRG) contains thousands of sensory neurons that transmit information about our external and internal environment to the central nervous system. This includes signals related to proprioception, temperature, and nociception. Our understanding of DRG has increased tremendously over the last 50 years and has established the DRG as an active participant in peripheral processes. This includes interactions between neurons and non-neuronal cells such as satellite glia cells and macrophages that contribute to an increasingly complex cellular environment that modulates neuronal function. Early ultrastructural investigations of the DRG have described subtypes of sensory neurons based on differences in the arrangement of organelles such as the Golgi apparatus and the endoplasmic reticulum. The neuron-satellite cell complex and the composition of the axon hillock in DRG have also been investigated, but, apart from basic descriptions of Schwann cells, ultrastructural investigations of other cell types in DRG are limited. Furthermore, detailed descriptions of key components of DRG, such as blood vessels and the capsule that sits at the intersection of the meninges and the connective tissue covering the peripheral nervous system, are lacking to date. With rising interest in DRG as potential therapeutic targets for aberrant signalling associated with chronic pain conditions, gaining further insights into DRG ultrastructure will be fundamental to understanding cell–cell interactions that modulate DRG function. In this review, we aim to provide a synopsis of the current state of knowledge on the ultrastructure of the DRG and its components, as well as to identify areas of interest for future studies.
... GLUT-3 was up-regulated in the SNI animals, and mainly expressed in astrocytes and microglia cells [22,44]. However, the GLUT-3 expression level was unchanged in sciatic nerve transection of the frogs [45]. Our team studies have pointed out that, EA treatment increased brain regional glucose metabolism and the expressions of GLUT-3 in neurons of the hippocampus and cortex, consequently alleviating cognitive impairment [28]. ...
Background
Accumulating evidence has demonstrated that the electroacupuncture (EA) stimulation could effectively alleviate neuropathic pain. The medial prefrontal cortex (mPFC) is a vital part of the cortical representation of pain in the brain, and its glucose metabolism is mostly affected in the progression of pain. However, the central mechanism of EA analgesia remains unclear.
Methods
Fifty-four male SD rats were equally randomized into sham surgery (Sham) group, chronic constriction injury (CCI) group and EA stimulation (EA) group. The CCI model, involving ligature of the right sciatic nerve, was established in all animals except the Sham group. EA stimulation was applied on the right side acupoints of Huantiao (GB30) and Yanglingquan (GB34) in the EA group. Paw withdrawal threshold (PWT) and paw thermal withdrawal latency (PWL) were measured. The ¹⁸ F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to evaluate glucose metabolism changes in the mPFC. The expression of glucose transporter 3 (GLUT-3) in the mPFC was determined by immune histochemistry and ELISA.
Results
Comparing with CCI groups, EA treatment was obviously reversed CCI-induced mechanical allodynia (P < 0.01), thermal hyperalgesia (P < 0.01) and the increase of glucose metabolism in the left mPFC (P < 0.05). Furthermore, EA treatment significantly decreased the protein expression of GLUT-3 in the left mPFC (P < 0.01).
Conclusions
Our results indicate that EA analgesia effect may be related to suppressing the glucose metabolism and GLUT-3 expression in the mPFC. This study could provide a potential insight into the central mechanisms involved in the analgesic effect of EA.
... MCT2 mRNA is also expressed in DRG neurons [4]. GLUTs have also not been thoroughly examined in DRG neurons, though a study in frogs suggests they express GLUT3, but not GLUT1 [77], and these metabolic transporters appear to be altered following peripheral nerve injury [78]. ...
Cellular metabolism is critical not only for cell survival, but also for cell fate, function, and intercellular communication. There are several different metabolic transporters expressed in the peripheral nervous system, and they each play important roles in maintaining cellular energy. The major source of energy in the peripheral nervous system is glucose, and glucose transporters 1 and 3 are expressed and allow blood glucose to be imported and utilized by peripheral nerves. There is also increasing evidence that other sources of energy, particularly monocarboxylates such as lactate that are transported primarily by monocarboxylate transporters 1 and 2 in peripheral nerves, can be efficiently utilized by peripheral nerves. Finally, emerging evidence supports an important role for connexins and possibly pannexins in the supply and regulation of metabolic energy. In this review, we will first define these critical metabolic transporter subtypes and then examine their localization in the peripheral nervous system. We will subsequently discuss the evidence, which comes both from experiments in animal models and observations from human diseases, supporting critical roles played by these metabolic transporters in the peripheral nervous system. Despite progress made in understanding the function of these transporters, many questions and some discrepancies remain, and these will also be addressed throughout this review. Peripheral nerve metabolism is fundamentally important and renewed interest in these pathways should help to answer many of these questions and potentially provide new treatments for neurologic diseases that are partly, or completely, caused by disruption of metabolism.
... This metabolic dysregulation is modelled by the authors as occurring within the cortex, with particular relevance to migraine with aura, and with effects that spread to brain pain centres. However, it should also be noted that GLUT1 is evident in satellite glial cells that enwrap sensory and nociceptive ganglia across species [61]. This may be of some importance as the effects of CGRP in vasodilation and the priming, and perhaps sensitization, of nociceptive ganglia are determined by satellite glial cell responses [62]. ...
The pathoetiology and pathophysiology of migraine are widely accepted as unknown. The current article overviews the wide array of data associated with the biological underpinnings of migraine and provides a framwork that integrates previously disparate bodies of data. The importance of alterations in stress- and pro-inflammatory cytokine- induced gut dysbiosis, especially butyrate production, is highlighted. This is linked to a decrease in the availability of melatonin, and a relative increase in the N-acetylserotonin/melatonin ratio, which has consequences for the increased glutamatergic excitatory transmission in migraine. It is proposed that suboptimal mitochondria functioning and metabolic regulation drive alterations in astrocytes and satellite glial cells that underpin the vasoregulatory and nociceptive changes in migraine. This provides a framework not only for classical migraine associated factors, such as calcitonin-gene related peptide and serotonin, but also for a developmental pathoetiology of migraine. A number of future research and treatment implications arise, including the clinical utilization of sodium butyrate and melatonin in the management of migraine.
... This metabolic dysregulation is modelled by the authors as occurring within the cortex, with particular relevance to migraine with aura, and with effects that spread to brain pain centres. However, it should also be noted that GLUT1 is evident in satellite glial cells that enwrap sensory and nociceptive ganglia across species [61]. This may be of some importance as the effects of CGRP in vasodilation and the priming, and perhaps sensitization, of nociceptive ganglia are determined by satellite glial cell responses [62]. ...
Background:
The pathoetiology and pathophysiology of migraine are widely accepted as unknown.
Methods:
The current article reviews the wide array of data associated with the biological underpinnings of migraine and provides a framework that integrates previously disparate bodies of data.
Results:
The importance of alterations in stress- and pro-inflammatory cytokine- induced gut dysbiosis, especially butyrate production, are highlighted. This is linked to a decrease in the availability of melatonin, and a relative increase in the N-acetylserotonin/melatonin ratio, which has consequences for the heightened glutamatergic excitatory transmission in migraine. It is proposed that suboptimal mitochondria functioning and metabolic regulation drive alterations in astrocytes and satellite glial cells that underpin the vasoregulatory and nociceptive changes in migraine.
Conclusion:
This provides a framework not only for classical migraine associated factors, such as calcitonin-gene related peptide and serotonin, but also for wider factors in the developmental pathoetiology of migraine. A number of future research and treatment implications arise, including the clinical utilization of sodium butyrate and melatonin in the management of migraine.
... The bullfrog Lithobates catesbeianus is an semiaquatic amphibian (Hedrick et al., 2015) native to the United States that was imported into Brazil in the early 1930s and has been raised in this country ever since (Rocha and Branco, 1998). This species has been used as a model for the study of SNT-induced neuropathic pain (Rigon et al., 2014(Rigon et al., , 2013Guedes et al., 2004a, b;Partata et al., 2002) because it provides a phylogenetic perspective on the mechanisms of pain research (Rigon et al., 2013). These studies reported alterations that shared similarities with those observed in mammals, while others were unique to this animal species. ...
... The bullfrog Lithobates catesbeianus is an semiaquatic amphibian (Hedrick et al., 2015) native to the United States that was imported into Brazil in the early 1930s and has been raised in this country ever since (Rocha and Branco, 1998). This species has been used as a model for the study of SNT-induced neuropathic pain (Rigon et al., 2014(Rigon et al., , 2013Guedes et al., 2004a, b;Partata et al., 2002) because it provides a phylogenetic perspective on the mechanisms of pain research (Rigon et al., 2013). These studies reported alterations that shared similarities with those observed in mammals, while others were unique to this animal species. ...
... The animals were fed ad libitum with the same food offered in farms, which was now offered on a vibration plate to move the pellets. The animals remained in the laboratory for at least 2 weeks before being used in the surgery, as described by Rigon et al. (2013). The aquarium water was periodically replaced with fresh tap water. ...
Sciatic nerve transection (SNT), a model for studying neuropathic pain, mimics the clinical symptoms of “phantom limb”, a pain condition that arises in humans after amputation or transverse spinal lesions. In some vertebrate tissues, this condition decreases acetylcholinesterase (AChE) activity, the enzyme responsible for fast hydrolysis of released acetylcholine in cholinergic synapses. In spinal cord of frog Rana pipiens, this enzyme’s activity was not significantly changed in the first days following ventral root transection, another model for studying neuropathic pain. An answerable question is whether SNT decreases AChE activity in spinal cord of frog Lithobates catesbeianus, a species that has been used as a model for studying SNT-induced neuropathic pain. Since each animal model has been created with a specific methodology, and the findings tend to vary widely with slight changes in the method used to induce pain, our study assessed AChE activity 3 and 10 days after complete SNT in lumbosacral spinal cord of adult male bullfrog Lithobates catesbeianus. Because there are time scale differences of motor endplate maturation in rat skeletal muscles, our study also measured the AChE activity in bullfrog tibial posticus (a postural muscle) and gastrocnemius (a typical skeletal muscle that is frequently used to study the motor system) muscles. AChE activity did not show significant changes 3 and 10 days following SNT in spinal cord. Also, no significant change occurred in AChE activity in tibial posticus and gastrocnemius muscles at day 3. However, a significant decrease was found at day 10, with reductions of 18% and 20% in tibial posticus and gastrocnemius, respectively. At present we cannot explain this change in AChE activity. While temporally different, the direction of the change was similar to that described for rats. This similarity indicates that bullfrog is a valid model for investigating AChE activity following SNT.
... To understand these regulations in the mouse DRG, we measured expression of c-fos, CGRP, and inflammatory cytokines in the cuff models. The expression of c-fos and activation of its protein FOS was correlated with neuronal activity in the DRG, which is often considered as a reflection of pain sensation [70,71]. CGRP is a pain-transmitting neuropeptide present in the DRG, which is always up-regulated in pain conditions [72]. ...
Melatonin (Mel) and its receptors (MT1 and MT2) have a well-documented efficacy in treating different pain conditions. However, the anti-nociceptive effects of Mel and Mel receptors in neuropathic pain (NP) are poorly understood. To elucidate this process, pain behaviors were measured in a dorsal root ganglia (DRG)-friendly sciatic nerve cuffing model. We detected up-regulation of MT2 expression in the DRGs of cuff-implanted mice and its activation by the agonist 8-M-PDOT (8MP). Also, Mel attenuated the mechanical and thermal allodynia induced by cuff implantation. Immunohistochemical analysis demonstrated the expression of MT2 in the DRG neurons, while MT1 was expressed in the satellite cells. In cultured primary neurons, microarray analysis and gene knockdown experiments demonstrated that MT2 activation by 8MP or Mel suppressed calcium signaling pathways via MAPK1, which were blocked by RAR-related orphan receptor alpha (RORα) activation with a high dose of Mel. Furthermore, expression of nitric oxide synthase 1 (NOS1) was down-regulated upon Mel treatment regardless of MT2 or RORα. Application of Mel or 8MP in cuff-implanted models inhibited the activation of peptidergic neurons and neuro-inflammation in the DRGs by down-regulating c-fos, calcitonin gene-related peptide [CGRP], and tumor necrosis factor-1α [TNF-1α] and interleukin-1β [IL-1β]. Addition of the MT2 antagonist luzindole blocked the effects of 8MP but not those of Mel. In conclusion, only MT2 was expressed in the DRG neurons and up-regulated upon cuff implantation. The analgesic effects of Mel in cuff-implanted mice were closely associated with both MT2-dependent (MAPK-calcium channels) and MT2-independent (NOS1) pathways in the DRG.
... Many of these alterations share similarities with those observed in mammals (Partata et al., 2002;Guedes et al., 2004a, b). As glucose has been considered the major energy substrate for the frog brain (McDougal et al., 1968), glucose transporters (Glut) types 1 and 3 are found in the nervous tissue of these animals (Rigon et al., 2013) and they accumulate lactic acid under some conditions (Warren and Jackson, 2005). Therefore we used frogs to demonstrate the effect of SNT on frog DRG 1-[ 14 C] 2-deoxy-D-glucose ( 14 C-2-DG) uptake in the presence and absence of lactate. ...
Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT), which mimics the clinical symptoms of "phantom limb", a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG) after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG) uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG) uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT.
... To provide insight into the early process of degeneration of myelinated axons within the first day after an injury, before Wallerian degeneration is normally observable, the development of an increased level of spatial structural resolution is needed, using non-invasive methods to bear in the biological realm. We have focussed our studies on this early stage of PNS degeneration by examining the myelin sheath of axons in the sciatic nerve of Xenopus frogs, a tissue that has been used previously to investigate the PNS degeneration [10][11] . ...
Degradation of the myelin sheath is a common pathology underlying demyelinating neurological diseases from Multiple Sclerosis to Leukodistrophies. Although large malformations of myelin ultrastructure in the advanced stages of Wallerian degradation is known, its subtle structural variations at early stages of demyelination remains poorly characterized. This is partly due to the lack of suitable and non-invasive experimental probes possessing sufficient resolution to detect the degradation. Here we report the feasibility of the application of an innovative non-invasive local structure experimental approach for imaging the changes of statistical structural fluctuations in the first stage of myelin degeneration. Scanning micro X-ray diffraction, using advances in synchrotron x-ray beam focusing, fast data collection, paired with spatial statistical analysis, has been used to unveil temporal changes in the myelin structure of dissected nerves following extraction of the Xenopus laevis sciatic nerve. The early myelin degeneration is a specific ordered compacted phase preceding the swollen myelin phase of Wallerian degradation. Our demonstration of the feasibility of the statistical analysis of SµXRD measurements using biological tissue paves the way for further structural investigations of degradation and death of neurons and other cells and tissues in diverse pathological states where nanoscale structural changes may be uncovered.
Purpose
We have re-evaluated the anatomical arguments that underlie the division of the spinal visceral outflow into sympathetic and parasympathetic divisions.
Methodology
Using a systematic literature search, we mapped the location of catecholaminergic neurons throughout the mammalian peripheral nervous system. Subsequently, a narrative method was employed to characterize segment-dependent differences in the location of preganglionic cell bodies and the composition of white and gray rami communicantes.
Results and Conclusion
One hundred seventy studies were included in the systematic review, providing information on 389 anatomical structures. Catecholaminergic nerve fibers are present in most spinal and all cranial nerves and ganglia, including those that are known for their parasympathetic function. Along the entire spinal autonomic outflow pathways, proximal and distal catecholaminergic cell bodies are common in the head, thoracic, and abdominal and pelvic region, which invalidates the “short-versus-long preganglionic neuron” argument.
Contrary to the classically confined outflow levels T1-L2 and S2-S4, preganglionic neurons have been found in the resulting lumbar gap. Preganglionic cell bodies that are located in the intermediolateral zone of the thoracolumbar spinal cord gradually nest more ventrally within the ventral motor nuclei at the lumbar and sacral levels, and their fibers bypass the white ramus communicans and sympathetic trunk to emerge directly from the spinal roots. Bypassing the sympathetic trunk, therefore, is not exclusive for the sacral outflow. We conclude that the autonomic outflow displays a conserved architecture along the entire spinal axis, and that the perceived differences in the anatomy of the autonomic thoracolumbar and sacral outflow are quantitative.
