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Use of non-biased stereology to estimate the number of TH+ neurons in the substantia nigra of 8 and 16 month old male and female C57BL/6 mice repeatedly exposed to paraquat and maneb.

O'Callaghan-JP; Kelly-KA; Miller-DB; Switzer-RC; Lau-EC; Li-AA; McIntosh-LJ
Toxicologist 2011 Mar; 120(Suppl 2):288-289
A proposed animal model for Parkinson's Disease is combined intraperitoneal exposure to paraquat (PQ) and maneb (MB) in C57Bl/6 mice. Stereologic methods were used to estimate tyrosine-hydroxylase positive (TH+) neuron number in the substantia nigra pars compacta (SNpc) of mice exposed to 3 dose levels of PQ+MB postnatally (PND) prior to weaning or both PND and as adults. Four groups of pups were dosed on PND 5-19 with 0/0, 0.3/1.0, 0.06/0.18, or 0.0007/0.0021 mg/kg PQ and MB (PQ/MB), respectively. These pups were divided into 3 sets of mice, each with 4 dose groups. One set dosed only PND was sacrificed at 8 months of age. Two sets were dosed again as adults twice weekly during weeks 27 to 31 of age with 0/0, 10/30 or 5/15, 0.6/1.8, or 0.0007/0.0021 mg/kg PQ/MB. (The scheduled 10/30 dose was reduced to 5/15 after adult male mortality occurred in one group). One set of PQ+MB groups dosed PND and as adults was sacrificed at 8 months of age, the other at 16 months of age. Brains of all animals were serially sectioned at 50 uM thickness, immunostained for TH, and counterstained for Nissl using thionine. Every 6th section in the SNpc was counted using stereological techniques with Stereo Investigator (MicrobrightField, Inc. Williston, VT) v9.0 software to give a non-biased number of TH+ cells in the SNpc using the optical fractionator method. A treatment-related decrease in SNpc TH+ neuron count was measured in high dose males dosed as pups and as adults and sacrificed at 16 months of age (n=5-6; p=0.06 Tukey-Kramer). There were no differences from controls in TH+ neuron number in females sacrificed at 16 months. At completion of the study, the total number of animals per group will be 8-11.
Biological-effects; Cell-biology; Cell-function; Cell-morphology; Cellular-reactions; Dose-response; Inhalation-studies; Laboratory-animals; Medical-research; Mortality-data; Neurological-reactions; Physiological-effects; Quantitative-analysis; Risk-analysis; Risk-factors; Statistical-analysis; Animal-studies; Animals; Central-nervous-system-disorders; Central-nervous-system; Brain-disorders
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The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC