Time course of neuropathology in the spinal cord of G86R superoxide dismutase transgenic mice

Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD‐1) gene, which corresponds to a mutation observed in familial amyotrophic lateral sclerosis (ALS), display progressive motor dysfunction leading to paralysis and premature death. In endstage SOD‐1 transgenic mice, there is m...

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Veröffentlicht in:Journal of comparative neurology (1911) 1998-02, Vol.391 (1), p.64-77
Hauptverfasser: Morrison, Brett M., Janssen, William G., Gordon, Jon W., Morrison, John H.
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Janssen, William G.
Gordon, Jon W.
Morrison, John H.
description Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD‐1) gene, which corresponds to a mutation observed in familial amyotrophic lateral sclerosis (ALS), display progressive motor dysfunction leading to paralysis and premature death. In endstage SOD‐1 transgenic mice, there is marked loss of spinal motor neurons and interneurons, accumulation of phosphorylated neurofilament inclusions, and reactive astrocytosis. The present study details the time course and ultrastructural appearance of these pathologic changes and correlates the timing of these events with the behavioral symptoms. There is no significant reduction in the number of total neurons, motor neurons, or interneurons in the ventral spinal cord of presymptomatic mice, as compared to age‐matched control mice. In contrast, there is a significant reduction in the number of total neurons (−23.5%), motor neurons (‐28.9%), and interneurons (‐23.5%) in symptomatic SOD‐1 transgenic mice. This neuron loss correlates temporally with the onset of reactive astrocytosis and the appearance of phosphorylated neurofilament inclusions. The identical timing of motor neuron and interneuron degeneration in this model of ALS strongly suggests that degeneration in the spinal cord of patients with ALS is not specifically directed at motor neurons, but rather more generally at several populations of neurons in the spinal cord. In addition, the late onset and rapid progression of neuron loss suggest that a toxic property is accumulating while the SOD‐1 transgenic mice are presymptomatic, and that this toxic property must reach a threshold level before the onset of neuronal degeneration. J. Comp. Neurol. 391:64–77, 1998. © 1998 Wiley‐Liss, Inc.
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In endstage SOD‐1 transgenic mice, there is marked loss of spinal motor neurons and interneurons, accumulation of phosphorylated neurofilament inclusions, and reactive astrocytosis. The present study details the time course and ultrastructural appearance of these pathologic changes and correlates the timing of these events with the behavioral symptoms. There is no significant reduction in the number of total neurons, motor neurons, or interneurons in the ventral spinal cord of presymptomatic mice, as compared to age‐matched control mice. In contrast, there is a significant reduction in the number of total neurons (−23.5%), motor neurons (‐28.9%), and interneurons (‐23.5%) in symptomatic SOD‐1 transgenic mice. This neuron loss correlates temporally with the onset of reactive astrocytosis and the appearance of phosphorylated neurofilament inclusions. The identical timing of motor neuron and interneuron degeneration in this model of ALS strongly suggests that degeneration in the spinal cord of patients with ALS is not specifically directed at motor neurons, but rather more generally at several populations of neurons in the spinal cord. In addition, the late onset and rapid progression of neuron loss suggest that a toxic property is accumulating while the SOD‐1 transgenic mice are presymptomatic, and that this toxic property must reach a threshold level before the onset of neuronal degeneration. J. Comp. 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Comp. Neurol</addtitle><description>Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD‐1) gene, which corresponds to a mutation observed in familial amyotrophic lateral sclerosis (ALS), display progressive motor dysfunction leading to paralysis and premature death. In endstage SOD‐1 transgenic mice, there is marked loss of spinal motor neurons and interneurons, accumulation of phosphorylated neurofilament inclusions, and reactive astrocytosis. The present study details the time course and ultrastructural appearance of these pathologic changes and correlates the timing of these events with the behavioral symptoms. There is no significant reduction in the number of total neurons, motor neurons, or interneurons in the ventral spinal cord of presymptomatic mice, as compared to age‐matched control mice. In contrast, there is a significant reduction in the number of total neurons (−23.5%), motor neurons (‐28.9%), and interneurons (‐23.5%) in symptomatic SOD‐1 transgenic mice. This neuron loss correlates temporally with the onset of reactive astrocytosis and the appearance of phosphorylated neurofilament inclusions. The identical timing of motor neuron and interneuron degeneration in this model of ALS strongly suggests that degeneration in the spinal cord of patients with ALS is not specifically directed at motor neurons, but rather more generally at several populations of neurons in the spinal cord. In addition, the late onset and rapid progression of neuron loss suggest that a toxic property is accumulating while the SOD‐1 transgenic mice are presymptomatic, and that this toxic property must reach a threshold level before the onset of neuronal degeneration. J. Comp. Neurol. 391:64–77, 1998. © 1998 Wiley‐Liss, Inc.</description><subject>amyotrophic lateral sclerosis</subject><subject>Animals</subject><subject>astrocytes</subject><subject>Astrocytes - pathology</subject><subject>Behavior, Animal - physiology</subject><subject>Cell Count</subject><subject>Cell Death - physiology</subject><subject>electron microscopy</subject><subject>Inclusion Bodies - pathology</subject><subject>interneurons</subject><subject>Interneurons - pathology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Immunoelectron</subject><subject>motor neurons</subject><subject>Motor Neurons - pathology</subject><subject>Mutation</subject><subject>Nerve Degeneration - pathology</subject><subject>Spinal Cord - pathology</subject><subject>Superoxide Dismutase - genetics</subject><subject>Tissue Embedding</subject><issn>0021-9967</issn><issn>1096-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1v0zAUhi0EGmXwE5ByhbaLFNtJnLigSVO2lYpqnaAaExI6cp3TzSNf2Im2_nscWsoFSMgX9pFeP-_RQ8gJo2NGKX979HmWz44ZlSKUmWBHTMqMcsqPI8km7L2IJ5PT2VmYX56Lk2hMx_niHQ-vnpDR_stTMvIgFkop0ufkhXP3lFIpo-yAHMiEp0nMR-Tb0lQY6Ka3DoNmHdTY26ZV3V1TNrebwNRBd4eBa02tSh-zxRCaZuJT4PoWbfNoCgwK46q-U57QWVW7W6yNDiqj8SV5tlalw1e7-5AsL86X-YdwvpjO8tN5qGO_XchXqP1J0lRnSmU0SzKMGKdxSjUvisi_lGIrHeNgIGbJWmBUCL3S6ZpTFh2SN1tsa5sfPboOKuM0lqWqsekdMMGFiHnsg9fboLaNcxbX0FpTKbsBRmHQDjBoh8EhDA7ht3bw2oGBiAG8dhi0QwQU8gVwuPLg17sN-lWFxR678_yn-MGUuPmr9b-l_-j8NXtwuAUb1-HjHqzsdxBplCbw5XIKX-nFzc31cg4fo59-Rq09</recordid><startdate>19980202</startdate><enddate>19980202</enddate><creator>Morrison, Brett M.</creator><creator>Janssen, William G.</creator><creator>Gordon, Jon W.</creator><creator>Morrison, John H.</creator><general>John Wiley &amp; Sons, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>19980202</creationdate><title>Time course of neuropathology in the spinal cord of G86R superoxide dismutase transgenic mice</title><author>Morrison, Brett M. ; Janssen, William G. ; Gordon, Jon W. ; Morrison, John H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4996-2becece577c8aa80858e3120470c2dd3204aa1bc4e0202415f6e3d6cbc7f2013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>amyotrophic lateral sclerosis</topic><topic>Animals</topic><topic>astrocytes</topic><topic>Astrocytes - pathology</topic><topic>Behavior, Animal - physiology</topic><topic>Cell Count</topic><topic>Cell Death - physiology</topic><topic>electron microscopy</topic><topic>Inclusion Bodies - pathology</topic><topic>interneurons</topic><topic>Interneurons - pathology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Immunoelectron</topic><topic>motor neurons</topic><topic>Motor Neurons - pathology</topic><topic>Mutation</topic><topic>Nerve Degeneration - pathology</topic><topic>Spinal Cord - pathology</topic><topic>Superoxide Dismutase - genetics</topic><topic>Tissue Embedding</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morrison, Brett M.</creatorcontrib><creatorcontrib>Janssen, William G.</creatorcontrib><creatorcontrib>Gordon, Jon W.</creatorcontrib><creatorcontrib>Morrison, John H.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Journal of comparative neurology (1911)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morrison, Brett M.</au><au>Janssen, William G.</au><au>Gordon, Jon W.</au><au>Morrison, John H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Time course of neuropathology in the spinal cord of G86R superoxide dismutase transgenic mice</atitle><jtitle>Journal of comparative neurology (1911)</jtitle><addtitle>J. Comp. Neurol</addtitle><date>1998-02-02</date><risdate>1998</risdate><volume>391</volume><issue>1</issue><spage>64</spage><epage>77</epage><pages>64-77</pages><issn>0021-9967</issn><eissn>1096-9861</eissn><abstract>Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD‐1) gene, which corresponds to a mutation observed in familial amyotrophic lateral sclerosis (ALS), display progressive motor dysfunction leading to paralysis and premature death. In endstage SOD‐1 transgenic mice, there is marked loss of spinal motor neurons and interneurons, accumulation of phosphorylated neurofilament inclusions, and reactive astrocytosis. The present study details the time course and ultrastructural appearance of these pathologic changes and correlates the timing of these events with the behavioral symptoms. There is no significant reduction in the number of total neurons, motor neurons, or interneurons in the ventral spinal cord of presymptomatic mice, as compared to age‐matched control mice. In contrast, there is a significant reduction in the number of total neurons (−23.5%), motor neurons (‐28.9%), and interneurons (‐23.5%) in symptomatic SOD‐1 transgenic mice. This neuron loss correlates temporally with the onset of reactive astrocytosis and the appearance of phosphorylated neurofilament inclusions. The identical timing of motor neuron and interneuron degeneration in this model of ALS strongly suggests that degeneration in the spinal cord of patients with ALS is not specifically directed at motor neurons, but rather more generally at several populations of neurons in the spinal cord. In addition, the late onset and rapid progression of neuron loss suggest that a toxic property is accumulating while the SOD‐1 transgenic mice are presymptomatic, and that this toxic property must reach a threshold level before the onset of neuronal degeneration. J. Comp. Neurol. 391:64–77, 1998. © 1998 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>9527542</pmid><doi>10.1002/(SICI)1096-9861(19980202)391:1&lt;64::AID-CNE6&gt;3.0.CO;2-P</doi><tpages>14</tpages></addata></record>
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ispartof Journal of comparative neurology (1911), 1998-02, Vol.391 (1), p.64-77
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subjects amyotrophic lateral sclerosis
Animals
astrocytes
Astrocytes - pathology
Behavior, Animal - physiology
Cell Count
Cell Death - physiology
electron microscopy
Inclusion Bodies - pathology
interneurons
Interneurons - pathology
Mice
Mice, Transgenic
Microscopy, Immunoelectron
motor neurons
Motor Neurons - pathology
Mutation
Nerve Degeneration - pathology
Spinal Cord - pathology
Superoxide Dismutase - genetics
Tissue Embedding
title Time course of neuropathology in the spinal cord of G86R superoxide dismutase transgenic mice
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