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Neurochemical Evidence for Agmatine Modulation of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Neurotoxicity

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Abstract

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.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 7 Plugot Street, Tel Aviv, 67639, Israel

    Gad M. Gilad & Varda H. Gilad

  2. Department of Life Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

    Gad M. Gilad

  3. Department of Pharmacology, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    John P. M. Finberg

  4. Department of Neurology, Assaf Harofeh Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Zrifin, Israel

    Jose M. Rabey

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  1. Gad M. Gilad
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  4. Jose M. Rabey
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Correspondence to Gad M. Gilad.

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Gilad, G.M., Gilad, V.H., Finberg, J.P. et al. Neurochemical Evidence for Agmatine Modulation of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Neurotoxicity. Neurochem Res 30, 713–719 (2005). https://doi.org/10.1007/s11064-005-6865-9

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