Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss |
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| Institution: | 1. Department of Entomology, Cornell University, Geneva, NY 14456, USA;2. Monsanto Company, St. Louis, MO, USA;3. College of Life Sciences, Nankai University, Tianjin 300071, China;1. Swiss Centre for Applied Human Toxicology (SCAHT), Switzerland;2. Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland;3. Department of Psychiatry, Centre for Psychiatric Neuroscience, Lausanne University Hospital, CHUV, Lausanne, Switzerland;1. Neuroscience Research Unit, Centre de Recherche du CHU de Québec, CHUL, 2705 Laurier Boulevard, Quebec City, Qc G1V 4G2, Canada;2. Faculty of Pharmacy, Laval University, 1050, Avenue de la Médecine, Quebec City, Qc G1V 0A6, Canada;3. Med-Life Discoveries LP, 104-407 Downey Road, Saskatoon, SK S7N 4L8, Canada;1. Centre for Applied Neurogenetics, Canada;2. Division of Neurology, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada;3. Isis Pharmaceuticals Inc, 2855 Gazelle Court, Carlsbad, CA 92010, USA;4. Dept. of Medical Sciences, Section of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, 44121 Ferrara, Italy;1. Department of Toxicology, Public Health School, Harbin Medical University, 150081, No 157, Baojian Road, Nangang District, Harbin City, Heilongjiang Province, China;2. Department of Acupuncture, Heilongjiang Academy of Chinese Medical Sciences, 150036, No 142, Sanfu Street, Xiangfang District, Harbin City, Heilongjiang Province, China;1. Department of Physiology, Emory University, Atlanta, GA, United States;2. Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States;3. Department of Biomedical Sciences, University of Cagliari, Italy |
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| Abstract: | Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons. Here, we determined the effect of a single intraperitoneal injection of one of three doses of MPTP (0.1, 2 and 20 mg/kg) on dopamine neurons, labeled by tyrosine hydroxylase (TH+), and total neuron number (Nissl+) in the SNc using unbiased stereological counting. Data reveal a significant loss of neurons in the SNc (TH+ and Nissl+) only in the group treated with 20 mg/kg MPTP. Groups treated with lower dose of MPTP (0.1 and 2 mg/kg) only showed significant loss of TH+ neurons rather than TH+ and Nissl+ neurons. Striatal dopamine levels were decreased in the groups treated with 2 and 20 mg/kg MPTP and striatal terminal markers including, TH and the dopamine transporter (DAT), were only decreased in the groups treated with 20 mg/kg MPTP. These data demonstrate that lower doses of MPTP likely result in loss of TH expression rather than actual dopamine neuron loss in the SN. This finding reinforces the need to measure both total neuron number along with TH+ cells in determining dopamine neuron loss. |
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| Keywords: | MPTP Stereology Tyrosine hydroxylase Dopamine transporter Vesicular monoamine transporter Dopamine |
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