Abstract
We have studied the in vivo effect of the selective agonist for group II metabotropic glutamate receptors (2S, 2'R, 3'R)-2-(2'3'-dicarboxycyclopropyl)glycine (DCG-IV) against MPP+-induced toxicity on rat striatal dopaminergic nerve terminals by using both microdialysis and immunohistochemical techniques. Perfusion of 1 mM DCG-IV during 1 h protected dopaminergic nerve terminals against the degeneration induced by a 15-minute perfusion of 1 mM MPP+. In addition, the microglial cell population was markedly activated 24 h after DCG-IV perfusion. The astroglial cell population was only markedly activated around the microdialysis probe. This protective effect seems to be dependent on protein synthesis since 1 mM cycloheximide, an inhibitor of protein synthesis, abolished the neuroprotective effect of 1 mM DCG-IV against MPP+ toxicity. Perfusion of DCG-IV induced an upregulation of striatal brain-derived neurotrophic factor (BDNF) mRNA expressing cells which were confined precisely around the microdialysis probe. Taken together, our results suggest that the induction and release of brain-derived neurotrophic factor (BDNF) by activated glial cells induced by DCG-IV perfusion may account for its protective action against MPP+-induced dopaminergic terminal degeneration.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
Animals
-
Benzoates / pharmacology
-
Brain-Derived Neurotrophic Factor / genetics
-
Brain-Derived Neurotrophic Factor / metabolism
-
Corpus Striatum / cytology
-
Corpus Striatum / drug effects
-
Corpus Striatum / metabolism*
-
Cyclopropanes / pharmacology
-
Disease Models, Animal
-
Dopamine / analysis
-
Dopamine / metabolism
-
Dopamine Agents
-
Excitatory Amino Acid Agonists / pharmacology*
-
Excitatory Amino Acid Antagonists / pharmacology
-
Glycine / analogs & derivatives*
-
Glycine / pharmacology
-
Immunohistochemistry
-
In Situ Hybridization
-
MPTP Poisoning / chemically induced
-
MPTP Poisoning / pathology
-
MPTP Poisoning / prevention & control*
-
Male
-
Microdialysis
-
Microglia / drug effects
-
Microglia / metabolism
-
Microglia / pathology
-
Neurons / drug effects
-
Neurons / metabolism
-
Neurons / pathology
-
Presynaptic Terminals / drug effects
-
Presynaptic Terminals / metabolism*
-
Protein Synthesis Inhibitors / pharmacology
-
RNA, Messenger / metabolism
-
Rats
-
Rats, Wistar
-
Receptors, Metabotropic Glutamate / agonists
-
Receptors, Metabotropic Glutamate / metabolism*
Substances
-
Benzoates
-
Brain-Derived Neurotrophic Factor
-
Cyclopropanes
-
Dopamine Agents
-
Excitatory Amino Acid Agonists
-
Excitatory Amino Acid Antagonists
-
Protein Synthesis Inhibitors
-
RNA, Messenger
-
Receptors, Metabotropic Glutamate
-
alpha-methyl-4-carboxyphenylglycine
-
2-(2,3-dicarboxycyclopropyl)glycine
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
Glycine
-
Dopamine