TY - JOUR
T1 - A metabotropic glutamate receptor agonist regulates neurotrophin messenger RNA in rat forebrain
AU - Murray, Karl D
AU - Wood, P. L.
AU - Rosasco, C.
AU - Isackson, P. J.
PY - 1996/2
Y1 - 1996/2
N2 - We have examined the role of metabotropic glutamate receptor activation in regulating neurotrophin messenger RNA levels in the brain with the use of the selective agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid. Intracerebroventricular injection of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid into adult rats resulted in increased expression of nerve growth factor and brain-derived neurotrophic factor messenger RNA in the hippocampus and pyriform cortex and decreased levels of neurotrophin-3 messenger RNA in the hippocampal dentate gyrus granule cell layer. C-fos messenger RNA levels were also increased throughout hippocampal and cortical subfields following (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid administration. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced changes in messenger RNA levels occurred without behavioral seizures, yet these changes were similar in magnitude and time course to early changes in neurotrophin and c-fos messenger RNA levels observed following recurrent limbic seizures. In contrast quisqualate, a potent agonist of metabotropic as well as ionotropic kainate/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, was only capable of inducing increased expression of brain-derived neurotrophic factor messenger RNA at doses which produced recurrent motor seizures, and both effects were completely inhibited by the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Neurotrophin messenger RNA changes induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid were also partially susceptible to 6-cyano-7-nitroquinoxaline-2,3-dione antagonism, as well as the specific N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10, 11-dihydroxy-5H-dibenzo(a,d)-cyclohepten-5,10-iminedizoleipine. These results suggest that (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive metabotropic glutamate receptors can dramatically increase the expression of neurotrophin and c-fos messenger RNAs in rat forebrain without producing significant behavioral trauma and that these influences may involve ionotropic glutamate receptors in certain brain regions.
AB - We have examined the role of metabotropic glutamate receptor activation in regulating neurotrophin messenger RNA levels in the brain with the use of the selective agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid. Intracerebroventricular injection of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid into adult rats resulted in increased expression of nerve growth factor and brain-derived neurotrophic factor messenger RNA in the hippocampus and pyriform cortex and decreased levels of neurotrophin-3 messenger RNA in the hippocampal dentate gyrus granule cell layer. C-fos messenger RNA levels were also increased throughout hippocampal and cortical subfields following (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid administration. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced changes in messenger RNA levels occurred without behavioral seizures, yet these changes were similar in magnitude and time course to early changes in neurotrophin and c-fos messenger RNA levels observed following recurrent limbic seizures. In contrast quisqualate, a potent agonist of metabotropic as well as ionotropic kainate/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, was only capable of inducing increased expression of brain-derived neurotrophic factor messenger RNA at doses which produced recurrent motor seizures, and both effects were completely inhibited by the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Neurotrophin messenger RNA changes induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid were also partially susceptible to 6-cyano-7-nitroquinoxaline-2,3-dione antagonism, as well as the specific N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10, 11-dihydroxy-5H-dibenzo(a,d)-cyclohepten-5,10-iminedizoleipine. These results suggest that (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive metabotropic glutamate receptors can dramatically increase the expression of neurotrophin and c-fos messenger RNAs in rat forebrain without producing significant behavioral trauma and that these influences may involve ionotropic glutamate receptors in certain brain regions.
KW - 1s
KW - 3R-ACPD
KW - BDNF
KW - c-fos
KW - hippocampus
KW - NGF
KW - NT-3
UR - http://www.scopus.com/inward/record.url?scp=0030058730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030058730&partnerID=8YFLogxK
U2 - 10.1016/S0306-4522(96)83002-8
DO - 10.1016/S0306-4522(96)83002-8
M3 - Article
C2 - 9045076
AN - SCOPUS:0030058730
VL - 70
SP - 617
EP - 630
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 3
ER -