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Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice.
PLoS One. 2016; 11(10):e0164094.Plos

Abstract

The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. MPTP activated microglia in the SNpc and increased the number of astrocytes in the SNpc and striatum.

Authors+Show Affiliations

St. Jude Children's Research Hospital, Dept. of Developmental Neurobiology, 262 Danny Thomas Place, Memphis, TN 38105, United States of America.Syngenta Crop Protection, LLC, P.O. Box 18300, Greensboro, NC 27419-8300, United States of America.WIL Research Laboratories, LLC., Ashland, OH 44805, United States of America.St. Jude Children's Research Hospital, Dept. of Developmental Neurobiology, 262 Danny Thomas Place, Memphis, TN 38105, United States of America.Tox Path Specialists, LLC, 8747 Chestnut Grove Road, Frederick, MD 21701-2607, United States of America.Experimental Pathology Laboratories, Inc., 45600 Terminal Drive, Sterling, VA 20166, United States of America.Experimental Pathology Laboratories, Inc., 45600 Terminal Drive, Sterling, VA 20166, United States of America.Syngenta Crop Protection, LLC, P.O. Box 18300, Greensboro, NC 27419-8300, United States of America.Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, United Kingdom.Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, United Kingdom.Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, United Kingdom.University of Leicester, University Road, Leicester LE1 7RH, United Kingdom.Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27788145

Citation

Smeyne, Richard Jay, et al. "Assessment of the Effects of MPTP and Paraquat On Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice." PloS One, vol. 11, no. 10, 2016, pp. e0164094.
Smeyne RJ, Breckenridge CB, Beck M, et al. Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice. PLoS One. 2016;11(10):e0164094.
Smeyne, R. J., Breckenridge, C. B., Beck, M., Jiao, Y., Butt, M. T., Wolf, J. C., Zadory, D., Minnema, D. J., Sturgess, N. C., Travis, K. Z., Cook, A. R., Smith, L. L., & Botham, P. A. (2016). Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice. PloS One, 11(10), e0164094. https://doi.org/10.1371/journal.pone.0164094
Smeyne RJ, et al. Assessment of the Effects of MPTP and Paraquat On Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice. PLoS One. 2016;11(10):e0164094. PubMed PMID: 27788145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice. AU - Smeyne,Richard Jay, AU - Breckenridge,Charles B, AU - Beck,Melissa, AU - Jiao,Yun, AU - Butt,Mark T, AU - Wolf,Jeffrey C, AU - Zadory,Dan, AU - Minnema,Daniel J, AU - Sturgess,Nicholas C, AU - Travis,Kim Z, AU - Cook,Andrew R, AU - Smith,Lewis L, AU - Botham,Philip A, Y1 - 2016/10/27/ PY - 2015/11/30/received PY - 2016/09/20/accepted PY - 2016/10/28/pubmed PY - 2017/6/13/medline PY - 2016/10/28/entrez SP - e0164094 EP - e0164094 JF - PloS one JO - PLoS One VL - 11 IS - 10 N2 - The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. MPTP activated microglia in the SNpc and increased the number of astrocytes in the SNpc and striatum. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27788145/Assessment_of_the_Effects_of_MPTP_and_Paraquat_on_Dopaminergic_Neurons_and_Microglia_in_the_Substantia_Nigra_Pars_Compacta_of_C57BL/6_Mice_ L2 - https://dx.plos.org/10.1371/journal.pone.0164094 DB - PRIME DP - Unbound Medicine ER -