Received: NovemAccepted: SeptemPublished: October 27, 2016Ĭopyright: © 2016 Smeyne et al. (2016) Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice. MPTP activated microglia in the SNpc and increased the number of astrocytes in the SNpc and striatum.Ĭitation: Smeyne RJ, Breckenridge CB, Beck M, Jiao Y, Butt MT, Wolf JC, et al.
Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. In MPTP-treated mice, the number of TH + neurons in the SNpc was significantly decreased and the number of activated microglia increased. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. 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. 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). 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.
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. Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. 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). 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).
0 kommentar(er)
