Herpes Simplex Virus Vectors Overexpressing the Glucose Transporter Gene Protect Against Seizure-Induced Neuron Loss
We have generated herpes simplex virus (HSV) vectors vIE1GT and vα4GT bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the control of the human cytomegalovirus ie1 and HSV α4 promoters, respectively. We previously reported that such vectors enhance glucose uptake in hippoca...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1995-08, Vol.92 (16), p.7247-7251 |
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| creator | Lawrence, Matthew S. Ho, Dora Y. Dash, Rajesh Sapolsky, Robert M. |
| description | We have generated herpes simplex virus (HSV) vectors vIE1GT and vα4GT bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the control of the human cytomegalovirus ie1 and HSV α4 promoters, respectively. We previously reported that such vectors enhance glucose uptake in hippocampal cultures and the hippocampus. In this study we demonstrate that such vectors can maintain neuronal metabolism and reduce the extent of neuron loss in cultures after a period of hypoglycemia. Microinfusion of GT vectors into the rat hippocampus also reduces kainic acid-induced seizure damage in the CA3 cell field. Furthermore, delivery of the vector even after onset of the seizure is protective, suggesting that HSV-mediated gene transfer for neuroprotection need not be carried out in anticipation of neurologic crises. Using the bicistronic vector vα22βgalα4GT, which coexpresses both GT and the Escherichia coli lacZ marker gene, we further demonstrate an inverse correlation between the extent of vector expression in the dentate and the amount of CA3 damage resulting from the simultaneous delivery of kainic acid. |
| doi_str_mv | 10.1073/pnas.92.16.7247 |
| format | Article |
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We previously reported that such vectors enhance glucose uptake in hippocampal cultures and the hippocampus. In this study we demonstrate that such vectors can maintain neuronal metabolism and reduce the extent of neuron loss in cultures after a period of hypoglycemia. Microinfusion of GT vectors into the rat hippocampus also reduces kainic acid-induced seizure damage in the CA3 cell field. Furthermore, delivery of the vector even after onset of the seizure is protective, suggesting that HSV-mediated gene transfer for neuroprotection need not be carried out in anticipation of neurologic crises. Using the bicistronic vector vα22βgalα4GT, which coexpresses both GT and the Escherichia coli lacZ marker gene, we further demonstrate an inverse correlation between the extent of vector expression in the dentate and the amount of CA3 damage resulting from the simultaneous delivery of kainic acid.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.92.16.7247</identifier><identifier>PMID: 7638175</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Animals ; Brain ; Brain damage ; Cercopithecus aethiops ; Escherichia coli ; Gene Expression ; Gene Transfer Techniques ; Genes ; Genetic Vectors ; Glucose Transporter Type 1 ; herpes simplex virus ; Herpes viruses ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hippocampus - pathology ; Hypoglycemia ; Hypoglycemia - metabolism ; Hypoglycemia - pathology ; In Vitro Techniques ; Infections ; Kainic Acid - toxicity ; Male ; Metabolism ; Monosaccharide Transport Proteins - genetics ; Neurology ; Neurons ; Neurons - metabolism ; Neurons - pathology ; Neuroscience ; Rats ; Rats, Sprague-Dawley ; Rodents ; Seizures ; Seizures - metabolism ; Seizures - pathology ; Seizures - prevention & control ; Simplexvirus ; Simplexvirus - genetics ; Vero Cells</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1995-08, Vol.92 (16), p.7247-7251</ispartof><rights>Copyright 1995 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Aug 1, 1995</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-c4e6c1d70769ed921e131f2abecca5d2d14db501810d1a24ae947800430db4c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/92/16.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2368221$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2368221$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7638175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lawrence, Matthew S.</creatorcontrib><creatorcontrib>Ho, Dora Y.</creatorcontrib><creatorcontrib>Dash, Rajesh</creatorcontrib><creatorcontrib>Sapolsky, Robert M.</creatorcontrib><title>Herpes Simplex Virus Vectors Overexpressing the Glucose Transporter Gene Protect Against Seizure-Induced Neuron Loss</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We have generated herpes simplex virus (HSV) vectors vIE1GT and vα4GT bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the control of the human cytomegalovirus ie1 and HSV α4 promoters, respectively. We previously reported that such vectors enhance glucose uptake in hippocampal cultures and the hippocampus. In this study we demonstrate that such vectors can maintain neuronal metabolism and reduce the extent of neuron loss in cultures after a period of hypoglycemia. Microinfusion of GT vectors into the rat hippocampus also reduces kainic acid-induced seizure damage in the CA3 cell field. Furthermore, delivery of the vector even after onset of the seizure is protective, suggesting that HSV-mediated gene transfer for neuroprotection need not be carried out in anticipation of neurologic crises. Using the bicistronic vector vα22βgalα4GT, which coexpresses both GT and the Escherichia coli lacZ marker gene, we further demonstrate an inverse correlation between the extent of vector expression in the dentate and the amount of CA3 damage resulting from the simultaneous delivery of kainic acid.</description><subject>Animals</subject><subject>Brain</subject><subject>Brain damage</subject><subject>Cercopithecus aethiops</subject><subject>Escherichia coli</subject><subject>Gene Expression</subject><subject>Gene Transfer Techniques</subject><subject>Genes</subject><subject>Genetic Vectors</subject><subject>Glucose Transporter Type 1</subject><subject>herpes simplex virus</subject><subject>Herpes viruses</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Hypoglycemia</subject><subject>Hypoglycemia - metabolism</subject><subject>Hypoglycemia - pathology</subject><subject>In Vitro Techniques</subject><subject>Infections</subject><subject>Kainic Acid - toxicity</subject><subject>Male</subject><subject>Metabolism</subject><subject>Monosaccharide Transport Proteins - genetics</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neuroscience</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Seizures</subject><subject>Seizures - metabolism</subject><subject>Seizures - pathology</subject><subject>Seizures - prevention & control</subject><subject>Simplexvirus</subject><subject>Simplexvirus - genetics</subject><subject>Vero Cells</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1vEzEQxVcIVELhzAWQxQFOm469znpX4lJVkFaKKFKjXi3HnqQbbeytP6rQv76OEiLKgdMc3u-9GfsVxXsKYwqiOhusCuOWjWk9FoyLF8WIQkvLmrfwshgBMFE2nPHXxZsQ1gDQTho4KU5EXTVUTEZFvEQ_YCA33WbocUtuO58CuUUdnQ_k-gE9bgePIXR2ReIdkmmftAtI5l7ZMDgf0ZMpWiS_vIvZRs5XqrMhkhvsHpPH8sqapNGQn5i8s2TmQnhbvFqqPuC7wzwt5j--zy8uy9n19OrifFbqCYNYao61pkaAqFs0LaNIK7pkaoFaq4lhhnKzmABtKBiqGFfYctEA8ArMguvqtPi2jx3SYoNGo41e9XLw3Ub539KpTj5XbHcnV-5B8rynzvYvB7t39wlDlJsuaOx7ZdGlIGndCFaLKoOf_wHXLnmbXyYZUNZCJjN0toe0zz_gcXm8g4LcVSl3VcqW5Vy5qzI7Pv59_pE_dJf1Twd9Z_yjPgv4-l9ALlPfR9zGTH7Yk-uQez-irKobxmj1BFsVvqM</recordid><startdate>19950801</startdate><enddate>19950801</enddate><creator>Lawrence, Matthew S.</creator><creator>Ho, Dora Y.</creator><creator>Dash, Rajesh</creator><creator>Sapolsky, Robert M.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>5PM</scope></search><sort><creationdate>19950801</creationdate><title>Herpes Simplex Virus Vectors Overexpressing the Glucose Transporter Gene Protect Against Seizure-Induced Neuron Loss</title><author>Lawrence, Matthew S. ; Ho, Dora Y. ; Dash, Rajesh ; Sapolsky, Robert M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-c4e6c1d70769ed921e131f2abecca5d2d14db501810d1a24ae947800430db4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Brain</topic><topic>Brain damage</topic><topic>Cercopithecus aethiops</topic><topic>Escherichia coli</topic><topic>Gene Expression</topic><topic>Gene Transfer Techniques</topic><topic>Genes</topic><topic>Genetic Vectors</topic><topic>Glucose Transporter Type 1</topic><topic>herpes simplex virus</topic><topic>Herpes viruses</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Hypoglycemia</topic><topic>Hypoglycemia - metabolism</topic><topic>Hypoglycemia - pathology</topic><topic>In Vitro Techniques</topic><topic>Infections</topic><topic>Kainic Acid - toxicity</topic><topic>Male</topic><topic>Metabolism</topic><topic>Monosaccharide Transport Proteins - genetics</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neuroscience</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Seizures</topic><topic>Seizures - metabolism</topic><topic>Seizures - pathology</topic><topic>Seizures - prevention & control</topic><topic>Simplexvirus</topic><topic>Simplexvirus - genetics</topic><topic>Vero Cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lawrence, Matthew S.</creatorcontrib><creatorcontrib>Ho, Dora Y.</creatorcontrib><creatorcontrib>Dash, Rajesh</creatorcontrib><creatorcontrib>Sapolsky, Robert M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lawrence, Matthew S.</au><au>Ho, Dora Y.</au><au>Dash, Rajesh</au><au>Sapolsky, Robert M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Herpes Simplex Virus Vectors Overexpressing the Glucose Transporter Gene Protect Against Seizure-Induced Neuron Loss</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1995-08-01</date><risdate>1995</risdate><volume>92</volume><issue>16</issue><spage>7247</spage><epage>7251</epage><pages>7247-7251</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>We have generated herpes simplex virus (HSV) vectors vIE1GT and vα4GT bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the control of the human cytomegalovirus ie1 and HSV α4 promoters, respectively. We previously reported that such vectors enhance glucose uptake in hippocampal cultures and the hippocampus. In this study we demonstrate that such vectors can maintain neuronal metabolism and reduce the extent of neuron loss in cultures after a period of hypoglycemia. Microinfusion of GT vectors into the rat hippocampus also reduces kainic acid-induced seizure damage in the CA3 cell field. Furthermore, delivery of the vector even after onset of the seizure is protective, suggesting that HSV-mediated gene transfer for neuroprotection need not be carried out in anticipation of neurologic crises. Using the bicistronic vector vα22βgalα4GT, which coexpresses both GT and the Escherichia coli lacZ marker gene, we further demonstrate an inverse correlation between the extent of vector expression in the dentate and the amount of CA3 damage resulting from the simultaneous delivery of kainic acid.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>7638175</pmid><doi>10.1073/pnas.92.16.7247</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1995-08, Vol.92 (16), p.7247-7251 |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Brain Brain damage Cercopithecus aethiops Escherichia coli Gene Expression Gene Transfer Techniques Genes Genetic Vectors Glucose Transporter Type 1 herpes simplex virus Herpes viruses Hippocampus - drug effects Hippocampus - metabolism Hippocampus - pathology Hypoglycemia Hypoglycemia - metabolism Hypoglycemia - pathology In Vitro Techniques Infections Kainic Acid - toxicity Male Metabolism Monosaccharide Transport Proteins - genetics Neurology Neurons Neurons - metabolism Neurons - pathology Neuroscience Rats Rats, Sprague-Dawley Rodents Seizures Seizures - metabolism Seizures - pathology Seizures - prevention & control Simplexvirus Simplexvirus - genetics Vero Cells |
| title | Herpes Simplex Virus Vectors Overexpressing the Glucose Transporter Gene Protect Against Seizure-Induced Neuron Loss |
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