Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP.
The mGluR5 antagonist MPEP was used to study the role of mGluR5 in MPTP-induced injury of the nigrostriatal DA neurons. The findings indicate that acute blockade of mGluR5 may result in neuroprotective actions against MPTP neurotoxicity on nigral DA cell bodies and striatal DA terminals using stereological analysis of TH immunoreactivity and microdensitometry. Biochemical analysis showed no restoration of DA levels and metabolism indicating a maintained reduction of DA transmission.
Aguirre
Jose A
JA
Department of Human Physiology, School of Medicine, Boulevard Luis Pasteur, 32, University of Málaga, 29071 Málaga, Spain. Jose.Aguirre@uma.es
Kehr
Jan
J
Yoshitake
Takashi
T
Liu
Fang-Ling
FL
Rivera
Alicia
A
Fernandez-Espinola
Sergio
S
Andbjer
Beth
B
Leo
Giuseppina
G
Medhurst
Andrew D
AD
Agnati
Luigi F
LF
Fuxe
Kjell
K
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine; D004298:Dopamine