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Previous Article | Next Article
The Journal of Neuroscience, January 1, 2000, 20(1):1-7
Mice Deficient in Cellular Glutathione Peroxidase Show Increased Vulnerability to Malonate, 3-Nitropropionic Acid, and 1-Methyl-4-Phenyl-1,2,5,6-Tetrahydropyridine
Peter Klivenyi1, Ole A. Andreassen1, Robert J. Ferrante2, Alpaslan Dedeoglu2, Gerald Mueller1, Eric Lancelot1, Mikhail Bogdanov1, Julie K. Andersen3, Dongmei Jiang3, and M. Flint Beal1, 4 1 Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 2 Departments of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts, and the Department of Veterans Affairs, Bedford, Massachusetts, 3 Department of Gerontology, University of Southern California, Los Angeles, California, and 4 Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021
Glutathione peroxidase (GSHPx) is a critical intracellular enzyme involved in detoxification of hydrogen peroxide (H2O2) to water. In the present study we examined the susceptibility of mice with a disruption of the glutathione peroxidase gene to the neurotoxic effects of malonate, 3-nitropropionic acid (3-NP), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Glutathione peroxidase knock-out mice showed no evidence of neuropathological or behavioral abnormalities at 2-3 months of age. Intrastriatal injections of malonate resulted in a significant twofold increase in lesion volume in homozygote GSHPx knock-out mice as compared to both heterozygote GSHPx knock-out and wild-type control mice. Malonate-induced increases in conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid, an index of hydroxyl radical generation, were greater in homozygote GSHPx knock-out mice as compared with both heterozygote GSHPx knock-out and wild-type control mice. Administration of MPTP resulted in significantly greater depletions of dopamine, 3,4-dihydroxybenzoic acid, and homovanillic acid in GSHPx knock-out mice than those seen in wild-type control mice. Striatal 3-nitrotyrosine (3-NT) concentrations after MPTP were significantly increased in GSHPx knock-out mice as compared with wild-type control mice. Systemic 3-NP administration resulted in significantly greater striatal damage and increases in 3-NT in GSHPx knock-out mice as compared to wild-type control mice. The present results indicate that a knock-out of GSHPx may be adequately compensated under nonstressed conditions, but that after administration of mitochondrial toxins GSHPx plays an important role in detoxifying increases in oxygen radicals.
Key words: MPTP; 3-nitropropionic acid; malonate; oxidative damage; free radicals; glutathione; Parkinson's; Huntington's
Copyright © 2000 Society for Neuroscience 0270-6474/0/2011-07$05.00/0
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E. M. Schuman, J. L. Dynes, and O. Steward
Synaptic regulation of translation of dendritic mRNAs.
J. Neurosci., July 5, 2006; 26(27): 7143 - 7146.
[Abstract] [Full Text] [PDF]
R. Bull, G. Blatto-Vallee, and M. Fabich
Subitizing, Magnitude Representation, and Magnitude Retrieval in Deaf and Hearing Adults
J. Deaf Stud. Deaf Educ., July 1, 2006; 11(3): 289 - 302.
[Abstract] [Full Text] [PDF]
V. Michel, Z. Yuan, S. Ramsubir, and M. Bakovic
Choline Transport for Phospholipid Synthesis.
Experimental Biology and Medicine, May 1, 2006; 231(5): 490 - 504.
[Abstract] [Full Text] [PDF]
R. Mejias, J. Villadiego, C. O. Pintado, P. J. Vime, L. Gao, J. J. Toledo-Aral, M. Echevarria, and J. Lopez-Barneo
Neuroprotection by transgenic expression of glucose-6-phosphate dehydrogenase in dopaminergic nigrostriatal neurons of mice.
J. Neurosci., April 26, 2006; 26(17): 4500 - 4508.
[Abstract] [Full Text] [PDF]
V. L. Katanaev and A. Tomlinson
Dual roles for the trimeric G protein Go in asymmetric cell division in Drosophila
PNAS, April 25, 2006; 103(17): 6524 - 6529.
[Abstract] [Full Text] [PDF]
M. H. Milekic, S. D. Brown, C. Castellini, and C. M. Alberini
Persistent disruption of an established morphine conditioned place preference.
J. Neurosci., March 15, 2006; 26(11): 3010 - 3020.
[Abstract] [Full Text] [PDF]
O. Ibanez-Sandoval, A. Hernandez, B. Floran, E. Galarraga, D. Tapia, R. Valdiosera, D. Erlij, J. Aceves, and J. Bargas
Control of the Subthalamic Innervation of Substantia Nigra Pars Reticulata by D1 and D2 Dopamine Receptors
J Neurophysiol, March 1, 2006; 95(3): 1800 - 1811.
[Abstract] [Full Text] [PDF]
D. Golomb, E. Ahissar, and D. Kleinfeld
Coding of Stimulus Frequency by Latency in Thalamic Networks Through the Interplay of GABAB-Mediated Feedback and Stimulus Shape
J Neurophysiol, March 1, 2006; 95(3): 1735 - 1750.
[Abstract] [Full Text] [PDF]
X. Dai, X. Cao, and D. L. Kreulen
Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase
Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1019 - H1026.
[Abstract] [Full Text] [PDF]
R. VanRullen, L. Reddy, and C. Koch
The Continuous Wagon Wheel Illusion Is Associated with Changes in Electroencephalogram Power at ~13 Hz
J. Neurosci., January 11, 2006; 26(2): 502 - 507.
[Abstract] [Full Text] [PDF]
Y.-H. Kim, M.-H. Ko, S.-Y. Na, S.-H. Park, and K.-W. Kim
Effects of single-dose methylphenidate on cognitive performance in patients with traumatic brain injury: a double-blind placebo-controlled study
Clinical Rehabilitation, January 1, 2006; 20(1): 24 - 30.
[Abstract] [PDF]
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