TY - JOUR
T1 - 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
AU - Sze, S. C. W.
AU - Wong, C. K. C.
AU - Yung, K. K. L.
N1 - Funding Information:
The present work was supported by Faculty Research Grant, Hong Kong Baptist University and Research Grant Council, Hong Kong. The authors would like to thank Miss L.Y. Man for technical assistance in the present project.
Publisher copyright:
© 2001 Elsevier Science Ltd. All rights reserved.
PY - 2001/10
Y1 - 2001/10
N2 - N-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.
AB - N-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.
KW - Basal ganglia
KW - Excitatory amino acid receptors
KW - Immunofluorescence
KW - Motor systems
KW - Pharmacology and modulation
KW - Physiology
KW - Reverse transcriptase-polymerase chain reaction
UR - http://www.scopus.com/inward/record.url?scp=0034868516&partnerID=8YFLogxK
U2 - 10.1016/S0197-0186(01)00032-8
DO - 10.1016/S0197-0186(01)00032-8
M3 - Journal article
C2 - 11551672
AN - SCOPUS:0034868516
SN - 0197-0186
VL - 39
SP - 319
EP - 327
JO - Neurochemistry International
JF - Neurochemistry International
IS - 4
ER -