Differential responsiveness to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in sub-regions of the primate substantia nigra and striatum |
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| Authors: | J D Elsworth A Y Deutch D E Redmond J R Sladek R H Roth |
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| Institution: | 1. Department of Pharmacology, Neurobehavioral Laboratory, and Department of Psychiatry Yale University School of Medicine 333 Cedar Street New Haven, Ct. 06510, U.S.A.;2. Department of Neurobiology and Anatomy University of Rochester School of Medicine & Dentistry 601 Elmwood Avenue Rochester, N.Y. 14642, U.S.A.;1. College of Safety Science and Engineering, Nanjing Tech University, Nanjing, 210009, Jiangsu Province, China;2. School of Environment and Safety Engineering, Changzhou University, Changzhou, 213164, Jiangsu Province, China;1. Joint Laboratory of Optics of Palacký University and Institute of Physics of Czech Academy of Sciences, 17. listopadu 12, 771 46 Olomouc, Czech Republic;2. Institute of Spintronics and Quantum Information, Adam Mickiewicz University, PL-61-614 Poznań, Poland;1. State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, No. 8 Xindu Avenue, Xindu District, Chengdu 610500, China;2. Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA;3. Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, Calgary T2N 1N4, Canada;1. College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, PR China;2. School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China;3. Department of Chemistry, Tsinghua University, Beijing 100084, PR China;1. Key Laboratory of Alpine Ecology, Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing 100101, China;2. CAS Center for Excellence in Tibetan Plateau Earth Sciences, Beijing 100101, China;3. University of Chinese Academy of Sciences, Beijing 100049, China;4. Research Center for Environmental Change, Academia Sinica, Taipei 115, China |
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| Abstract: | After treatment with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), there was a severe loss of dopamine (DA) at all examined sites in the striatum, both in those monkeys which remained asymptomatic (77-99%) and in one monkey which developed severe parkinsonian disability (94-99%). However, the asymptomatic animals had normal DA concentration in the substantia nigra (SN); yet in the symptomatic animal DA was largely depleted in the central (86%) and medial (94%), but not lateral (8%) regions of the SN. The HVA/DA ratio was raised in the striatum of all MPTP-treated animals. In the SN though, this ratio was elevated only in the symptomatic animal, in the central and medial, but not lateral regions. The contralateral half of these brains were examined for DA histofluorescence. The SN of asymptomatic animals had a slight increase in lipofuscin fluorescence within dopaminergic neurons and a small reduction in the number of dopaminergic cells, while fluorescent intensity of individual neurons was unchanged. The SN of the symptomatic animal displayed a sharp decline in the number of DA neurons along with an increase in autofluorescent pigment granules; these changes were most pronounced in the central and medial regions of the SN. These data suggest that after MPTP the terminals of the nigrostriatal pathway are affected before the cell bodies. In the one symptomatic animal emergence of parkinsonian disability corresponded with a marked loss of DA neurons and DA concentration in the central and medial regions of the SN. In the control monkeys a gradient in the concentration of amines and metabolites was observed within the SN; the lateral region contained the highest and the medial region the lowest concentration. |
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