Group II metabotropic glutamate receptor activation protects striatal dopaminergic nerve terminals against MPP+-induced neurotoxicity along with brain-derived neurotrophic factor induction

We have studied the in vivo effect of the selective agonist for group II me tabotropic glutamate receptors (2S, 2'R, 3'R)-2(2'3'-dicarboxycyclopropyl)g lycine (DCG-IV) against MPP+ induced toxicity on rat striatal dopaminergic nerve terminals by using both microdialysis and immunohistochemical techniq ues. Perfusion of 1 mM DCG-IV during Ih protected dopaminergic nerve termin als against the degeneration induced by a 15-minute perfusion of 1 mM MPP+. In addition, the microglial cell population was markedly activated 24 h af ter DCG-IV perfusion. The astroglial cell population was only markedly acti vated around the microdialysis probe. This protective effect seems to be de pendent on protein synthesis since 1 mM cycloheximide, an inhibitor of prot ein synthesis, abolished the neuroprotective effect of 1 mM DCG-IV against MPP+ toxicity. Perfusion of DCG-IV induced an upregulation of striatal brai n-derived neurotrophic factor (BDNF) mRNA expressing cells which were confi ned precisely around the microdialysis probe. Taken together, our results s uggest 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 degenerat ion.