Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats
Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of...
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| Veröffentlicht in: | Molecular neurobiology 2014-02, Vol.49 (1), p.276-287 |
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| creator | Tang, Peifu Hou, Hongping Zhang, Licheng Lan, Xia Mao, Zhi Liu, Daohong He, Chunqing Du, Hailong Zhang, Lihai |
| description | Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. In the present study, we examined the role of autophagy, inhibited by 3-MA and enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found that rapamycin could significantly increase the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the same time, the number of neurons and astrocytes with LC3 positive in the spinal cord was upregulated with time. In addition, administration of rapamycin produced an increase in the Basso, Beattie and Bresnahan scores of injured rats, indicating high recovery of locomotor function. Furthermore, expression of the proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By contrast, the results for rats treated with 3-MA, which inhibits autophagy, were the opposite of those seen with the rapamycin-treated rats. These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis. |
| doi_str_mv | 10.1007/s12035-013-8518-3 |
| format | Article |
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In the present study, we examined the role of autophagy, inhibited by 3-MA and enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found that rapamycin could significantly increase the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the same time, the number of neurons and astrocytes with LC3 positive in the spinal cord was upregulated with time. In addition, administration of rapamycin produced an increase in the Basso, Beattie and Bresnahan scores of injured rats, indicating high recovery of locomotor function. Furthermore, expression of the proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By contrast, the results for rats treated with 3-MA, which inhibits autophagy, were the opposite of those seen with the rapamycin-treated rats. These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-013-8518-3</identifier><identifier>PMID: 23954967</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; Apoptosis ; Apoptosis - physiology ; Autophagy ; Autophagy - drug effects ; Autophagy - physiology ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Male ; Motor Activity - drug effects ; Motor Activity - physiology ; Neurobiology ; Neurology ; Neurons ; Neurons - drug effects ; Neurons - pathology ; Neurosciences ; Rats ; Rats, Sprague-Dawley ; Recovery of Function - drug effects ; Recovery of Function - physiology ; Sirolimus - pharmacology ; Sirolimus - therapeutic use ; Spinal cord injuries ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - prevention & control ; Thoracic Vertebrae</subject><ispartof>Molecular neurobiology, 2014-02, Vol.49 (1), p.276-287</ispartof><rights>Springer Science+Business Media New York 2013</rights><rights>Springer Science+Business Media New York 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-e66450853f0315d0e891d6da1ef1052bb9f2a33c3b49112e63662d6cc611402f3</citedby><cites>FETCH-LOGICAL-c471t-e66450853f0315d0e891d6da1ef1052bb9f2a33c3b49112e63662d6cc611402f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-013-8518-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-013-8518-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23954967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Peifu</creatorcontrib><creatorcontrib>Hou, Hongping</creatorcontrib><creatorcontrib>Zhang, Licheng</creatorcontrib><creatorcontrib>Lan, Xia</creatorcontrib><creatorcontrib>Mao, Zhi</creatorcontrib><creatorcontrib>Liu, Daohong</creatorcontrib><creatorcontrib>He, Chunqing</creatorcontrib><creatorcontrib>Du, Hailong</creatorcontrib><creatorcontrib>Zhang, Lihai</creatorcontrib><title>Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. 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These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Autophagy - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Male</subject><subject>Motor Activity - drug effects</subject><subject>Motor Activity - physiology</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurons - drug effects</subject><subject>Neurons - pathology</subject><subject>Neurosciences</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recovery of Function - drug effects</subject><subject>Recovery of Function - physiology</subject><subject>Sirolimus - pharmacology</subject><subject>Sirolimus - 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Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Peifu</au><au>Hou, Hongping</au><au>Zhang, Licheng</au><au>Lan, Xia</au><au>Mao, Zhi</au><au>Liu, Daohong</au><au>He, Chunqing</au><au>Du, Hailong</au><au>Zhang, Lihai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>49</volume><issue>1</issue><spage>276</spage><epage>287</epage><pages>276-287</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. In the present study, we examined the role of autophagy, inhibited by 3-MA and enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found that rapamycin could significantly increase the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the same time, the number of neurons and astrocytes with LC3 positive in the spinal cord was upregulated with time. In addition, administration of rapamycin produced an increase in the Basso, Beattie and Bresnahan scores of injured rats, indicating high recovery of locomotor function. Furthermore, expression of the proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By contrast, the results for rats treated with 3-MA, which inhibits autophagy, were the opposite of those seen with the rapamycin-treated rats. These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23954967</pmid><doi>10.1007/s12035-013-8518-3</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Apoptosis Apoptosis - physiology Autophagy Autophagy - drug effects Autophagy - physiology Biomedical and Life Sciences Biomedicine Cell Biology Male Motor Activity - drug effects Motor Activity - physiology Neurobiology Neurology Neurons Neurons - drug effects Neurons - pathology Neurosciences Rats Rats, Sprague-Dawley Recovery of Function - drug effects Recovery of Function - physiology Sirolimus - pharmacology Sirolimus - therapeutic use Spinal cord injuries Spinal Cord Injuries - pathology Spinal Cord Injuries - prevention & control Thoracic Vertebrae |
| title | Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats |
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