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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

Correlation of PCB effects on Cyp2C11 mRNA levels and PCB effects on stroke outcome. Total RNA was extracted from the striatum of females (A, B) and males (C, D) at PND7 (A, C) and PND50 (B, D). Cyp2C11 mRNA was quantified by qRT-PCR and normalized against endogenous 18S RNA. Developmental exposure to A1254 at 0.1 or 1.0 mg/kg/day in the maternal diet significantly decreased Cyp2C11 mRNA expression in PND50 females (B), but had no effect on Cyp2C11 transcripts in the striatum of PND7 females (A) or males of either age (C, D). Data are presented as mean ± SE; n = 5–6 per treatment group per sex.*p < 0.05. #p < 0.001.
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f6-ehp0116-000474: Correlation of PCB effects on Cyp2C11 mRNA levels and PCB effects on stroke outcome. Total RNA was extracted from the striatum of females (A, B) and males (C, D) at PND7 (A, C) and PND50 (B, D). Cyp2C11 mRNA was quantified by qRT-PCR and normalized against endogenous 18S RNA. Developmental exposure to A1254 at 0.1 or 1.0 mg/kg/day in the maternal diet significantly decreased Cyp2C11 mRNA expression in PND50 females (B), but had no effect on Cyp2C11 transcripts in the striatum of PND7 females (A) or males of either age (C, D). Data are presented as mean ± SE; n = 5–6 per treatment group per sex.*p < 0.05. #p < 0.001.

Mentions: Developmental A1254 exposure had no effect on cortical or striatal levels of Bcl2 mRNA in either sex at PND7 (Figure 5A,C). In the PND50 brain, A1254 at 0.1 mg/kg/day reduced Bcl2 expression in the female cortex (Figure 5B), whereas both A1254 doses increased Bcl2 in the male cortex (Figure 5D). We next determined whether developmental A1254 exposure increased Cyp2C11 mRNA levels in the striatum of males or females at PND7 or PND50. The only significant effect was decreased Cyp2C11 transcription in PND50 females exposed developmentally to either A1254 dose (Figure 6).


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)

Correlation of PCB effects on Cyp2C11 mRNA levels and PCB effects on stroke outcome. Total RNA was extracted from the striatum of females (A, B) and males (C, D) at PND7 (A, C) and PND50 (B, D). Cyp2C11 mRNA was quantified by qRT-PCR and normalized against endogenous 18S RNA. Developmental exposure to A1254 at 0.1 or 1.0 mg/kg/day in the maternal diet significantly decreased Cyp2C11 mRNA expression in PND50 females (B), but had no effect on Cyp2C11 transcripts in the striatum of PND7 females (A) or males of either age (C, D). Data are presented as mean ± SE; n = 5–6 per treatment group per sex.*p < 0.05. #p < 0.001.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f6-ehp0116-000474: Correlation of PCB effects on Cyp2C11 mRNA levels and PCB effects on stroke outcome. Total RNA was extracted from the striatum of females (A, B) and males (C, D) at PND7 (A, C) and PND50 (B, D). Cyp2C11 mRNA was quantified by qRT-PCR and normalized against endogenous 18S RNA. Developmental exposure to A1254 at 0.1 or 1.0 mg/kg/day in the maternal diet significantly decreased Cyp2C11 mRNA expression in PND50 females (B), but had no effect on Cyp2C11 transcripts in the striatum of PND7 females (A) or males of either age (C, D). Data are presented as mean ± SE; n = 5–6 per treatment group per sex.*p < 0.05. #p < 0.001.
Mentions: Developmental A1254 exposure had no effect on cortical or striatal levels of Bcl2 mRNA in either sex at PND7 (Figure 5A,C). In the PND50 brain, A1254 at 0.1 mg/kg/day reduced Bcl2 expression in the female cortex (Figure 5B), whereas both A1254 doses increased Bcl2 in the male cortex (Figure 5D). We next determined whether developmental A1254 exposure increased Cyp2C11 mRNA levels in the striatum of males or females at PND7 or PND50. The only significant effect was decreased Cyp2C11 transcription in PND50 females exposed developmentally to either A1254 dose (Figure 6).

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