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Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.

Dziennis S, Yang D, Cheng J, Anderson KA, Alkayed NJ, Hurn PD, Lein PJ - Environ. Health Perspect. (2008)

Bottom Line: Developmental exposure to A1254 significantly decreased striatal infarct in females and males at 0.1 and 1 mg/kg/day, respectively.Predominantly ortho-substituted PCB congeners were detected above background levels in brains of adult females and males exposed to A1254 at 1 but not 0.1 mg/kg/day.Effects of developmental A1254 exposure on Bcl2 and Cyp2C11 expression did not correlate with effects on infarct volume.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Peri-Operative Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA.

ABSTRACT

Background: The "developmental origins of adult disease" hypothesis was originally derived from evidence linking low birth weight to cardiovascular diseases including stroke. Subsequently, it has been expanded to include developmental exposures to environmental contaminants as risk factors for adult onset disease.

Objective: Our goal in this study was to test the hypothesis that developmental exposure to poly-chlorinated biphenyls (PCBs) alters stroke outcome in adults.

Methods: We exposed rats to the PCB mixture Aroclor 1254 (A1254) at 0.1 or 1 mg/kg/day in the maternal diet throughout gestation and lactation. Focal cerebral ischemia was induced at 6-8 weeks of age via middle cerebral artery occlusion, and infarct size was measured in the cerebral cortex and striatum at 22 hr of reperfusion. PCB congeners were quantified in brain tissue by gas chromatography with microelectron capture detection, and cortical and striatal expression of Bcl2 and Cyp2C11 were quantified by quantitative reverse transcriptase-polymerase chain reaction.

Results: Developmental exposure to A1254 significantly decreased striatal infarct in females and males at 0.1 and 1 mg/kg/day, respectively. Predominantly ortho-substituted PCB congeners were detected above background levels in brains of adult females and males exposed to A1254 at 1 but not 0.1 mg/kg/day. Effects of developmental A1254 exposure on Bcl2 and Cyp2C11 expression did not correlate with effects on infarct volume.

Conclusion: Our data provide proof of principle that developmental exposures to environmental contaminants influence the response of the adult brain to ischemic injury and thus represent potentially important determinants of stroke susceptibility.

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Related in: MedlinePlus

Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on CYP activity in the liver of adult rats; see “Materials and Methods” for details. Activities of EROD (A) and PROD (B), biomarkers of exposure to coplanar and noncoplanar PCBs, respectively, were measured in hepatic microsomes from adult female (8–10 weeks of age) and male rats (6–8 weeks of age). Developmental PCB exposure caused a sex- and dose-dependent increase in both EROD and PROD activity. Data are presented as mean ± SE; n = 8 per treatment group per sex.*p < 0.05. **p < 0.01. #p < 0.001.
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f4-ehp0116-000474: Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on CYP activity in the liver of adult rats; see “Materials and Methods” for details. Activities of EROD (A) and PROD (B), biomarkers of exposure to coplanar and noncoplanar PCBs, respectively, were measured in hepatic microsomes from adult female (8–10 weeks of age) and male rats (6–8 weeks of age). Developmental PCB exposure caused a sex- and dose-dependent increase in both EROD and PROD activity. Data are presented as mean ± SE; n = 8 per treatment group per sex.*p < 0.05. **p < 0.01. #p < 0.001.

Mentions: A question raised by the stroke studies was why females were more sensitive to the neuroprotective effects of developmental A1254 exposure than males. One possible mechanism is differences in PCB metabolism between the sexes. As an indirect test of this hypothesis, we measured CYP activities in hepatic microsomes from animals receiving MCAO and quantified PCB brain levels in comparably aged litter-mates. In vehicle controls, EROD activity was similar between females and males; however, developmental A1254 exposure significantly increased EROD activity among females in the high-dose group but not among males in either A1254 dose group (Figure 4A). PROD activity was significantly higher among vehicle control males than among females, and developmental exposure to A1254 increased PROD activity in both females and males (Figure 4B). In females, this effect was observed only in the high-dose group, whereas in males, this effect was observed in both A1254 dose groups.


Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.

Dziennis S, Yang D, Cheng J, Anderson KA, Alkayed NJ, Hurn PD, Lein PJ - Environ. Health Perspect. (2008)

Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on CYP activity in the liver of adult rats; see “Materials and Methods” for details. Activities of EROD (A) and PROD (B), biomarkers of exposure to coplanar and noncoplanar PCBs, respectively, were measured in hepatic microsomes from adult female (8–10 weeks of age) and male rats (6–8 weeks of age). Developmental PCB exposure caused a sex- and dose-dependent increase in both EROD and PROD activity. Data are presented as mean ± SE; n = 8 per treatment group per sex.*p < 0.05. **p < 0.01. #p < 0.001.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2291013&req=5

f4-ehp0116-000474: Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on CYP activity in the liver of adult rats; see “Materials and Methods” for details. Activities of EROD (A) and PROD (B), biomarkers of exposure to coplanar and noncoplanar PCBs, respectively, were measured in hepatic microsomes from adult female (8–10 weeks of age) and male rats (6–8 weeks of age). Developmental PCB exposure caused a sex- and dose-dependent increase in both EROD and PROD activity. Data are presented as mean ± SE; n = 8 per treatment group per sex.*p < 0.05. **p < 0.01. #p < 0.001.
Mentions: A question raised by the stroke studies was why females were more sensitive to the neuroprotective effects of developmental A1254 exposure than males. One possible mechanism is differences in PCB metabolism between the sexes. As an indirect test of this hypothesis, we measured CYP activities in hepatic microsomes from animals receiving MCAO and quantified PCB brain levels in comparably aged litter-mates. In vehicle controls, EROD activity was similar between females and males; however, developmental A1254 exposure significantly increased EROD activity among females in the high-dose group but not among males in either A1254 dose group (Figure 4A). PROD activity was significantly higher among vehicle control males than among females, and developmental exposure to A1254 increased PROD activity in both females and males (Figure 4B). In females, this effect was observed only in the high-dose group, whereas in males, this effect was observed in both A1254 dose groups.

Bottom Line: Developmental exposure to A1254 significantly decreased striatal infarct in females and males at 0.1 and 1 mg/kg/day, respectively.Predominantly ortho-substituted PCB congeners were detected above background levels in brains of adult females and males exposed to A1254 at 1 but not 0.1 mg/kg/day.Effects of developmental A1254 exposure on Bcl2 and Cyp2C11 expression did not correlate with effects on infarct volume.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Peri-Operative Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA.

ABSTRACT

Background: The "developmental origins of adult disease" hypothesis was originally derived from evidence linking low birth weight to cardiovascular diseases including stroke. Subsequently, it has been expanded to include developmental exposures to environmental contaminants as risk factors for adult onset disease.

Objective: Our goal in this study was to test the hypothesis that developmental exposure to poly-chlorinated biphenyls (PCBs) alters stroke outcome in adults.

Methods: We exposed rats to the PCB mixture Aroclor 1254 (A1254) at 0.1 or 1 mg/kg/day in the maternal diet throughout gestation and lactation. Focal cerebral ischemia was induced at 6-8 weeks of age via middle cerebral artery occlusion, and infarct size was measured in the cerebral cortex and striatum at 22 hr of reperfusion. PCB congeners were quantified in brain tissue by gas chromatography with microelectron capture detection, and cortical and striatal expression of Bcl2 and Cyp2C11 were quantified by quantitative reverse transcriptase-polymerase chain reaction.

Results: Developmental exposure to A1254 significantly decreased striatal infarct in females and males at 0.1 and 1 mg/kg/day, respectively. Predominantly ortho-substituted PCB congeners were detected above background levels in brains of adult females and males exposed to A1254 at 1 but not 0.1 mg/kg/day. Effects of developmental A1254 exposure on Bcl2 and Cyp2C11 expression did not correlate with effects on infarct volume.

Conclusion: Our data provide proof of principle that developmental exposures to environmental contaminants influence the response of the adult brain to ischemic injury and thus represent potentially important determinants of stroke susceptibility.

Show MeSH
Related in: MedlinePlus