A metabotropic glutamate receptor agonist regulates neurotrophin messenger RNA in rat forebrain

• Published in: Neuroscience 1996-02, Vol.70 (3), p.617-630
• Main Authors: Murray, K.D., Wood, P.L., Rosasco, C., Isackson, P.J.
• Format: Article
• Language: English
• Subjects: 3R-ACPD; Animals; BDNF; Biochemistry and metabolism; Biological and medical sciences; Brain-Derived Neurotrophic Factor - genetics; c-fos; Central nervous system; Cycloleucine - analogs & derivatives; Cycloleucine - pharmacology; Fundamental and applied biological sciences. Psychology; In Situ Hybridization; Injections, Intraventricular; Lippocampus; Male; Nerve Growth Factors - genetics; Neurotrophin 3; NGF; NT-3; Prosencephalon - metabolism; Proto-Oncogene Proteins c-fos - genetics; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - drug effects; Receptors, Metabotropic Glutamate - physiology; RNA, Messenger - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(96)83002-8

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 (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid. Intracerebroventricular injection of (1 S,3 R)-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 (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid administration. (1 S,3 R)-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 (1 S,3 R)-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 (1 S,3 R)-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.