Neurochemical evidence for agmatine modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity.
Agmatine treatment is known to exert neuroprotective effects in several models of neurotoxic and ischemic brain and spinal cord injuries. Here we sought to find out whether agmatine treatment would also prove to be neuroprotective in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Concomitant daily treatment (intraperitoneal injections) with agmatine (100 mg/kg for 5 days) and MPTP (40 mg/kg for 2 days) exacerbated MPTP-related toxicity as evidenced by a larger reduction in dopamine uptake into striatal synaptosomes (42.4% as compared to 58.3% of control, respectively). In contrast, agmatine treatment commencing after MPTP, produced partial protection (31%) against MPTP dopaminergic toxicity. The findings implicate agmatine in mechanisms regulating MPTP neurotoxicity, but underscore the characteristic neuroprotective efficacy of agmatine when applied after the insult.
Gilad
Gad M
GM
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 7 Plugot Street, Tel Aviv 67639, Israel. gm-gilad@zahav.net.il
Gilad
Varda H
VH
Finberg
John P M
JP
Rabey
Jose M
JM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D000376:Agmatine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D008995:Monoamine Oxidase; D004298:Dopamine