Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg

Cindy S. Roegge, John R. Morris, Sherilyn Villareal, Victor C. Wang, Brian E. Powers, Anna Y. Klintsova, William T. Greenough, Isaac N Pessah, Susan L. Schantz

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)74-85
Number of pages12
JournalNeurotoxicology and Teratology
Volume28
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Purkinje Cells
Polychlorinated Biphenyls
Brain
Cerebellum
Rats
Animals
Chlorodiphenyl (54% Chlorine)
Long Evans Rats
Ryanodine Receptor Calcium Release Channel
Calcium Signaling
Dendrites
Weaning
Serum
Thyroid Hormones
Drinking Water
Dams
Breeding
Protein Isoforms
Cell Count
Calcium

Keywords

  • Cerebellum
  • Methylmercury (MeHg)
  • Paramedian lobule (PML)
  • Polychlorinated biphenyls (PCBs)
  • Purkinje cells
  • Ryanodine receptor
  • Thyroid hormones

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology

Cite this

Roegge, C. S., Morris, J. R., Villareal, S., Wang, V. C., Powers, B. E., Klintsova, A. Y., ... Schantz, S. L. (2006). Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg. Neurotoxicology and Teratology, 28(1), 74-85. https://doi.org/10.1016/j.ntt.2005.10.001

Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg. / Roegge, Cindy S.; Morris, John R.; Villareal, Sherilyn; Wang, Victor C.; Powers, Brian E.; Klintsova, Anna Y.; Greenough, William T.; Pessah, Isaac N; Schantz, Susan L.

In: Neurotoxicology and Teratology, Vol. 28, No. 1, 01.2006, p. 74-85.

Research output: Contribution to journalArticle

Roegge, CS, Morris, JR, Villareal, S, Wang, VC, Powers, BE, Klintsova, AY, Greenough, WT, Pessah, IN & Schantz, SL 2006, 'Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg', Neurotoxicology and Teratology, vol. 28, no. 1, pp. 74-85. https://doi.org/10.1016/j.ntt.2005.10.001
Roegge, Cindy S. ; Morris, John R. ; Villareal, Sherilyn ; Wang, Victor C. ; Powers, Brian E. ; Klintsova, Anna Y. ; Greenough, William T. ; Pessah, Isaac N ; Schantz, Susan L. / Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg. In: Neurotoxicology and Teratology. 2006 ; Vol. 28, No. 1. pp. 74-85.
@article{77f3747efe1b430f866f14a63900ad53,
title = "Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg",
abstract = "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.",
keywords = "Cerebellum, Methylmercury (MeHg), Paramedian lobule (PML), Polychlorinated biphenyls (PCBs), Purkinje cells, Ryanodine receptor, Thyroid hormones",
author = "Roegge, {Cindy S.} and Morris, {John R.} and Sherilyn Villareal and Wang, {Victor C.} and Powers, {Brian E.} and Klintsova, {Anna Y.} and Greenough, {William T.} and Pessah, {Isaac N} and Schantz, {Susan L.}",
year = "2006",
month = "1",
doi = "10.1016/j.ntt.2005.10.001",
language = "English (US)",
volume = "28",
pages = "74--85",
journal = "Neurotoxicology and Teratology",
issn = "0892-0362",
publisher = "Elsevier Inc.",
number = "1",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=32844456161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32844456161&partnerID=8YFLogxK

U2 - 10.1016/j.ntt.2005.10.001

DO - 10.1016/j.ntt.2005.10.001

M3 - Article

VL - 28

SP - 74

EP - 85

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

SN - 0892-0362

IS - 1

ER -