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Article: Modulation of the gene expression of N-methyl-D-aspartate receptor NR2B subunit in the rat neostriatum by a single dose of specific antisense oligodeoxynucleotide

TitleModulation of the gene expression of N-methyl-D-aspartate receptor NR2B subunit in the rat neostriatum by a single dose of specific antisense oligodeoxynucleotide
Authors
Issue Date2001
PublisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuint
Citation
Neurochemistry International, 2001, v. 39 n. 4, p. 319-327 How to Cite?
AbstractN-methyl-D-aspartate receptors (NRs) are a group of ionotropic glutamate receptors in the brain and they are composed of heteromeric subunits (NR1, NR2A-D and NR3). In the neostriatum, a brain region that is associated with movement in animals, NMDA channels are known to involve in the motor control. Our previous report (Lai et al., 2000, Neuroscience 98, 493-500) has shown that a single dose of antisense oligodeoxynucleotides that are specific to NR1 subunit results in blockage of the gene expression of NR1 as well as NR2A subunits in the neostriatum. In the present study, antisense oligodeoxynucleotides that are specific to NR2B (ANR2B) were then employed as molecular tools to further investigate the molecular interactions of NMDA receptor subunits in the neostriatum. A single dose of ANR2B was injected unilaterally into the rat neostriatum. After one day of injection, no modification of motor behavior was found in the ANR2B-injected rats. The mRNA level of NR2B in the ANR2B-injected neostriatum was found to be decreased (-20.4%) by reverse transcriptase polymerase chain reaction (RT-PCR). However, the mRNA levels of NR1, NR2A, NR2C and NR2D in the ANR2B-treated neostriatum were found to be unchanged. After two days of injection, NR2B immunoreactivity was found to decrease in the ANR2B-treated neostriatum by immunofluorescence (-35.1%). At higher magnification, NR2B immunoreactivity was found to decrease in presumed spiny neurons of the neostriatum (-23.4%). No change in NR1 immunoreactivity was observed. These results indicate that a single dose of ANR2B can successfully block the gene expression of NR2B in neurons of the neostriatum and there is less effect on NR1 and other NR2 subunits. The blockage of the gene expression of NR2B is therefore specific and the present results may provide important implications in applications of antisense in research and in clinical therapy of neurological diseases. © 2001 Elsevier Science Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179409
ISSN
2015 Impact Factor: 3.385
2015 SCImago Journal Rankings: 1.345
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSze, SCWen_US
dc.contributor.authorWong, CKCen_US
dc.contributor.authorYung, KKLen_US
dc.date.accessioned2012-12-19T09:56:14Z-
dc.date.available2012-12-19T09:56:14Z-
dc.date.issued2001en_US
dc.identifier.citationNeurochemistry International, 2001, v. 39 n. 4, p. 319-327en_US
dc.identifier.issn0197-0186en_US
dc.identifier.urihttp://hdl.handle.net/10722/179409-
dc.description.abstractN-methyl-D-aspartate receptors (NRs) are a group of ionotropic glutamate receptors in the brain and they are composed of heteromeric subunits (NR1, NR2A-D and NR3). In the neostriatum, a brain region that is associated with movement in animals, NMDA channels are known to involve in the motor control. Our previous report (Lai et al., 2000, Neuroscience 98, 493-500) has shown that a single dose of antisense oligodeoxynucleotides that are specific to NR1 subunit results in blockage of the gene expression of NR1 as well as NR2A subunits in the neostriatum. In the present study, antisense oligodeoxynucleotides that are specific to NR2B (ANR2B) were then employed as molecular tools to further investigate the molecular interactions of NMDA receptor subunits in the neostriatum. A single dose of ANR2B was injected unilaterally into the rat neostriatum. After one day of injection, no modification of motor behavior was found in the ANR2B-injected rats. The mRNA level of NR2B in the ANR2B-injected neostriatum was found to be decreased (-20.4%) by reverse transcriptase polymerase chain reaction (RT-PCR). However, the mRNA levels of NR1, NR2A, NR2C and NR2D in the ANR2B-treated neostriatum were found to be unchanged. After two days of injection, NR2B immunoreactivity was found to decrease in the ANR2B-treated neostriatum by immunofluorescence (-35.1%). At higher magnification, NR2B immunoreactivity was found to decrease in presumed spiny neurons of the neostriatum (-23.4%). No change in NR1 immunoreactivity was observed. These results indicate that a single dose of ANR2B can successfully block the gene expression of NR2B in neurons of the neostriatum and there is less effect on NR1 and other NR2 subunits. The blockage of the gene expression of NR2B is therefore specific and the present results may provide important implications in applications of antisense in research and in clinical therapy of neurological diseases. © 2001 Elsevier Science Ltd. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuinten_US
dc.relation.ispartofNeurochemistry Internationalen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApomorphine - Pharmacologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshFluorescent Antibody Techniqueen_US
dc.subject.meshGene Expression Regulation - Geneticsen_US
dc.subject.meshMotor Activity - Drug Effectsen_US
dc.subject.meshNeostriatum - Drug Effects - Metabolismen_US
dc.subject.meshOligonucleotides, Antisense - Pharmacologyen_US
dc.subject.meshRna, Messenger - Biosynthesisen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReceptors, N-Methyl-D-Aspartate - Genetics - Metabolismen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshStereotyped Behavior - Drug Effectsen_US
dc.titleModulation of the gene expression of N-methyl-D-aspartate receptor NR2B subunit in the rat neostriatum by a single dose of specific antisense oligodeoxynucleotideen_US
dc.typeArticleen_US
dc.identifier.emailSze, SCW: stephens@hku.hken_US
dc.identifier.authoritySze, SCW=rp00514en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0197-0186(01)00032-8en_US
dc.identifier.pmid11551672-
dc.identifier.scopuseid_2-s2.0-0034868516en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034868516&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume39en_US
dc.identifier.issue4en_US
dc.identifier.spage319en_US
dc.identifier.epage327en_US
dc.identifier.isiWOS:000171597700007-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridSze, SCW=23482617000en_US
dc.identifier.scopusauthoridWong, CKC=35276549400en_US
dc.identifier.scopusauthoridYung, KKL=13605496000en_US

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