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Lawrence D. F. Moon - One of the best experts on this subject based on the ideXlab platform.
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Chromatolysis: Do injured axons regenerate poorly when ribonucleases attack rough endoplasmic reticulum, ribosomes and RNA?
Developmental Neurobiology, 2018Co-Authors: Lawrence D. F. MoonAbstract:After axonal injury, Chromatolysis (fragmentation of Nissl substance) can occur in the soma. Electron microscopy shows that Chromatolysis involves fission of the rough endoplasmic reticulum. In CNS neurons (which do not regenerate axons back to their original targets) or in motor neurons or dorsal root ganglion neurons denied axon regeneration (e.g., by transection and ligation), Chromatolysis is often accompanied by degranulation (loss of ribosomes from rough endoplasmic reticulum), disaggregation of polyribosomes and degradation of monoribosomes into dust-like particles. Ribosomes and rough endoplasmic reticulum may also be degraded in autophagic vacuoles by ribophagy and reticulophagy, respectively. In other words, Chromatolysis is disruption of parts of the protein synthesis infrastructure. Whereas some neurons may show transient or no Chromatolysis, severely injured neurons can remain chromatolytic and never again synthesize normal levels of protein; some may atrophy or die. Ribonuclease(s) might cause the following features of Chromatolysis: fragmentation and degranulation of rough endoplasmic reticulum, disaggregation of polyribosomes and degradation of monoribosomes. For example, ribonucleases in the EndoU/PP11 family can modify rough endoplasmic reticulum; many ribonucleases can degrade mRNA causing polyribosomes to unchain and disperse, and they can disassemble monoribosomes; Ribonuclease 5 can control rRNA synthesis and degrade tRNA; Ribonuclease T2 can degrade ribosomes, endoplasmic reticulum and RNA within autophagic vacuoles; and Ribonuclease IRE1α acts as a stress sensor within the endoplasmic reticulum. Regeneration might be improved after axonal injury by protecting the protein synthesis machinery from catabolism; targeting ribonucleases using inhibitors can enhance neurite outgrowth and could be a profitable strategy in vivo. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018.
Shuuichi Yamada - One of the best experts on this subject based on the ideXlab platform.
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Pathology of lumbar nerve root compression. Part 2: morphological and immunohistochemical changes of dorsal root ganglion.
Journal of Orthopaedic Research, 2004Co-Authors: Shigeru Kobayashi, Hidezo Yoshizawa, Shuuichi YamadaAbstract:Study design: This study is to investigate the changes of dorsal root ganglion (DRG) induced by mechanical compression using in vivo model. Objectives: The effect of axonal flow disturbance induced by nerve root compression was determined in DRG. Summary of background data: The dorsal root ganglion should not be overlooked when considering the mechanism of low back pain and sciatica, so it is important to understand the morphologic and functional changes that occur in primary sensory neurons of the dorsal root ganglion as a result of nerve root compression. However, few studies have looked at changes of neurons within the dorsal root ganglion caused by disturbance of axonal flow and the axon reaction as a result of mechanical compression of the dorsal root through which the central branches of the primary sensory nerves pass. Methods: In mongrel dogs, the seventh lumbar nerve root was compressed for 24 h, one week, or three weeks using a clip with a pressure of 7.5 gf. Morphologic changes of the primary sensory neurons in the dorsal root ganglion secondary to the axon reaction were examined by light and electron microscopy. Changes of immunostaining for substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SOM) in the primary sensory neurons affected by central Chromatolysis after nerve root compression were also examined. Results: Light microscopy showed central Chromatolysis of neurons in the dorsal root ganglion from one week after the start of compression. Electron microscopy of the affected neurons revealed movement of the nucleus to the cell periphery and the loss of rough endo-plasmic reticulum and mitochondria from the central region. Immunohistochemical studies showed a marked decrease of SP, CGRP, and SOM staining in small ganglion cells with central Chromatolysis when compared with cells from control ganglia. Conclusion: It is important to be aware that in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression, but also extends to the primary sensory neurons within the dorsal root ganglion as a result of the axon reaction. Patients with sensory disturbance should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.
Toshio Mizutani - One of the best experts on this subject based on the ideXlab platform.
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spinal anterior horn cells in sporadic amyotrophic lateral sclerosis show ribosomal detachment from and cisternal distention of the rough endoplasmic reticulum
Neuropathology and Applied Neurobiology, 2008Co-Authors: Kiyomitsu Oyanagi, Mineo Yamazaki, Hitoshi Takahashi, Kazuhiko Watabe, Manabu Wada, Tetsuo Komori, Takashi Morita, Toshio MizutaniAbstract:Aims Sporadic amyotrophic lateral sclerosis (ALS) is a progressive and invariably fatal disease involving the upper and lower motor neurones of adult humans. Among the neuropathological features of the disease, abnormalities in the protein-synthesizing system in motor neurones of the brainstem and spinal cord, such as a decrease of cytoplasmic RNA and rough endoplasmic reticulum (rER) (Chromatolysis), defective editing of the Q/R site of the glutamate receptor subunit GluR2 mRNA, fragmentation of the Golgi apparatus and accumulation of ubiquitinated inclusions and abnormal TdP-43 protein have been reported to be essential for the degeneration. In relation to these features, although the possibility of ER stress has been reported in motor neurones of the brainstem and spinal cord of ALS patients, the rER itself has not been a main target of ultrastructural investigation. Methods The present study examined the rER, ultrastructurally and quantitatively in the spinal anterior horn cells (AHCs) of 21 Japanese patients with sporadic ALS and eight Japanese control subjects. Results and conclusions It was found that: (i) the rER cisternae in AHCs showing central Chromatolysis were fragmented, but retained their width and had normally attached ribosomes, and (ii) the rER cisternae in shrunken AHCs were irregularly distended with detachment of the ribosomes, thus suggesting that (iii) ribosomal detachment was related to rER distention.
Shigeru Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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Pathology of lumbar nerve root compression. Part 2: morphological and immunohistochemical changes of dorsal root ganglion.
Journal of Orthopaedic Research, 2004Co-Authors: Shigeru Kobayashi, Hidezo Yoshizawa, Shuuichi YamadaAbstract:Study design: This study is to investigate the changes of dorsal root ganglion (DRG) induced by mechanical compression using in vivo model. Objectives: The effect of axonal flow disturbance induced by nerve root compression was determined in DRG. Summary of background data: The dorsal root ganglion should not be overlooked when considering the mechanism of low back pain and sciatica, so it is important to understand the morphologic and functional changes that occur in primary sensory neurons of the dorsal root ganglion as a result of nerve root compression. However, few studies have looked at changes of neurons within the dorsal root ganglion caused by disturbance of axonal flow and the axon reaction as a result of mechanical compression of the dorsal root through which the central branches of the primary sensory nerves pass. Methods: In mongrel dogs, the seventh lumbar nerve root was compressed for 24 h, one week, or three weeks using a clip with a pressure of 7.5 gf. Morphologic changes of the primary sensory neurons in the dorsal root ganglion secondary to the axon reaction were examined by light and electron microscopy. Changes of immunostaining for substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SOM) in the primary sensory neurons affected by central Chromatolysis after nerve root compression were also examined. Results: Light microscopy showed central Chromatolysis of neurons in the dorsal root ganglion from one week after the start of compression. Electron microscopy of the affected neurons revealed movement of the nucleus to the cell periphery and the loss of rough endo-plasmic reticulum and mitochondria from the central region. Immunohistochemical studies showed a marked decrease of SP, CGRP, and SOM staining in small ganglion cells with central Chromatolysis when compared with cells from control ganglia. Conclusion: It is important to be aware that in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression, but also extends to the primary sensory neurons within the dorsal root ganglion as a result of the axon reaction. Patients with sensory disturbance should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.
Yong Chul Kim - One of the best experts on this subject based on the ideXlab platform.
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| Original Article | Therapeutic Effect of Epidurally Administered
2016Co-Authors: Lipo-prostaglandin E, Francis Sahngun Nahm, Agonist Rat, Spinal Stenosis Model, Yong Chul KimAbstract:A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. Methods: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, 0.15 μg.kg-1 of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of Chromatolysis, chronic inflammation, and fibrosis in light microscopic images. Results: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P ＜ 0.05). Microscopic analysis showed much less Chromatolysis in the EP group than in the saline or control groups
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Therapeutic effect of epidurally administered lipo-prostaglandin e1 agonist in a rat spinal stenosis model.
The Korean journal of pain, 2014Co-Authors: Sang Hyun Park, Pyung Bok Lee, Ghee Young Choe, Jee Yeon Moon, Francis Sahngun Nahm, Yong Chul KimAbstract:BACKGROUND A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. METHODS A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, 0.15 µg.kg-1 of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of Chromatolysis, chronic inflammation, and fibrosis in light microscopic images. RESULTS From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less Chromatolysis in the EP group than in the saline or control groups. CONCLUSIONS An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing Chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.