TY - JOUR
T1 - Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg
AU - Roegge, Cindy S.
AU - Morris, John R.
AU - Villareal, Sherilyn
AU - Wang, Victor C.
AU - Powers, Brian E.
AU - Klintsova, Anna Y.
AU - Greenough, William T.
AU - Pessah, Isaac N.
AU - Schantz, Susan L.
N1 - Funding Information:
The authors would like to thank Dr. John Widholm, who assisted in the dosing of these animals, and Kristen Bergland, who examined Purkinje cell structure for abnormalities. Dr. Andrew Phimister and Kyung Ho Kim are acknowledged for contributing the RyR Western blot and [ 3 H] ryanodine binding analyses, respectively. We would also like to thank Dr. Julie Markham, Dr. Roberto Galvez, Shawn Kohler, and Jennifer Boklewski for their technical advice. This research was supported by EPA R-828 95301, EPA R-82939001, NIH AA09838 and AG10154, NIEHS PO1 ES11263 and PO1 ES11269. In addition, Victor C. Wang was supported on NIEHS T32 ES07326 during conduct of the research and preparation of the manuscript.
PY - 2006/1
Y1 - 2006/1
N2 - We recently reported that rats exposed to PCBs and MeHg during development were impaired on the rotating rod, a test of balance and coordination that is often indicative of cerebellar damage. In addition, developmental PCB exposure is known to dramatically reduce circulating thyroid hormone concentrations, which may have a negative impact on cerebellar development. Therefore, we investigated the effects of combined PCB and MeHg exposure on Purkinje cells and the cerebellum. The serum and brains from littermates of the animals tested on the rotating rod were collected at weaning, and we also collected brains from the adult animals at the end of motor testing. Four groups were studied: 1) vehicle controls, 2) PCBs only (Aroclor 1254, 6 mg/kg/d, oral), 3) MeHg only (0.5 ppm, in dams' drinking water), and 4) PCB + MeHg (at the same doses as in individual toxicant exposures). Female Long-Evans rats were exposed beginning 4 weeks prior to breeding with an unexposed male and continuing until postnatal day (PND) 16. There was a significant reduction in serum T4 and T3 concentrations in the PCB and PCB + MeHg pups on PND21. Golgi-impregnated Purkinje cells were examined in PND21 brains, but there were no significant exposure-related effects on primary dendrite length, branching area, or structural abnormalities. However, all three male exposure groups had a marginally significant increase in Purkinje cell height, which may suggest a subtle thyromimetic effect in the cerebellum. Cresyl-violet stained sections from the adult brains showed no exposure-related effects within paramedian lobule in Purkinje cell number, total lobule volume or layer volumes (molecular, granule cell and white matter layers). Evidence is provided for the dysregulation of expression of cerebellar ryanodine receptor (RyR) isoforms in PCB-exposed brains, and this could contribute to the rotating rod deficit by changing critical aspects of intracellular calcium signaling within the cerebellum.
AB - We recently reported that rats exposed to PCBs and MeHg during development were impaired on the rotating rod, a test of balance and coordination that is often indicative of cerebellar damage. In addition, developmental PCB exposure is known to dramatically reduce circulating thyroid hormone concentrations, which may have a negative impact on cerebellar development. Therefore, we investigated the effects of combined PCB and MeHg exposure on Purkinje cells and the cerebellum. The serum and brains from littermates of the animals tested on the rotating rod were collected at weaning, and we also collected brains from the adult animals at the end of motor testing. Four groups were studied: 1) vehicle controls, 2) PCBs only (Aroclor 1254, 6 mg/kg/d, oral), 3) MeHg only (0.5 ppm, in dams' drinking water), and 4) PCB + MeHg (at the same doses as in individual toxicant exposures). Female Long-Evans rats were exposed beginning 4 weeks prior to breeding with an unexposed male and continuing until postnatal day (PND) 16. There was a significant reduction in serum T4 and T3 concentrations in the PCB and PCB + MeHg pups on PND21. Golgi-impregnated Purkinje cells were examined in PND21 brains, but there were no significant exposure-related effects on primary dendrite length, branching area, or structural abnormalities. However, all three male exposure groups had a marginally significant increase in Purkinje cell height, which may suggest a subtle thyromimetic effect in the cerebellum. Cresyl-violet stained sections from the adult brains showed no exposure-related effects within paramedian lobule in Purkinje cell number, total lobule volume or layer volumes (molecular, granule cell and white matter layers). Evidence is provided for the dysregulation of expression of cerebellar ryanodine receptor (RyR) isoforms in PCB-exposed brains, and this could contribute to the rotating rod deficit by changing critical aspects of intracellular calcium signaling within the cerebellum.
KW - Cerebellum
KW - Methylmercury (MeHg)
KW - Paramedian lobule (PML)
KW - Polychlorinated biphenyls (PCBs)
KW - Purkinje cells
KW - Ryanodine receptor
KW - Thyroid hormones
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U2 - 10.1016/j.ntt.2005.10.001
DO - 10.1016/j.ntt.2005.10.001
M3 - Article
C2 - 16309888
AN - SCOPUS:32844456161
SN - 0892-0362
VL - 28
SP - 74
EP - 85
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
IS - 1
ER -