Grantee Research Project Results
2012 Progress Report: Effects of Bisphenol A on the Developing Cortex
EPA Grant Number: R834593C004Subproject: this is subproject number 004 , established and managed by the Center Director under grant R834593
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Water Innovation Network for Sustainable Small Systems
Center Director: Reckhow, David A.
Title: Effects of Bisphenol A on the Developing Cortex
Investigators: Schantz, Susan L. , Juraska, Janice , Flaws, Jodi
Current Investigators: Juraska, Janice
Institution: University of Illinois Urbana-Champaign
EPA Project Officer: Hahn, Intaek
Project Period: February 15, 2010 through February 14, 2014
Project Period Covered by this Report: February 15, 2012 through February 14,2013
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Cognitive neural functions are influenced by gonadal hormones and may be altered by endocrine disruptors including bisphenol A (BPA). This pilot project models the effects of BPA in hooded rats, an animal model where sex differences in the cerebral cortex have been documented and are known to be influenced by the hormonal milieu during both the perinatal and peripubertal period. The effects of BPA on neuron number, a very basic building block of function, are being explored in the medial prefrontal cortex, where sex differences have been found. The number of neurons are being quantified with stereological methods. Rats exposed to BPA either perinatally or peripubertally are being evaluated. In addition to its established sex differences in neuron number, the medial prefrontal cortex plays a role in behaviors analogous to those that are being assessed in human infants and adolescents in Projects 1 and 2. Thus, the behavioral consequences of cortical alterations also are being investigated in a visual spatial task, the radial arm maze, which consistently shows sex differences in several laboratories. Four doses of BPA (0, 4, 40 or 400 µg/kg/day) are fed to male and female rats during early development (prenatally to dams and 10 days postnatally) or during adolescence (days 27-46). Both cognitive behavior (17-arm radial maze) and cortical neuron number are quantified when the animals are adults (>90 days). An addendum onto the original design is that observations of maternal behavior over the first 15 postnatal days has been added to the early development experiment.
Progress Summary:
In the perinatal exposure groups, maternal behavior was monitored for the first 15 postnatal days. Some doses of BPA were found to increase maternal licking over controls. The group exposed to 40 µg/kg/day had significantly more licking than controls and the 4 µg/kg/day group also showed a trend toward more licking. The group exposed to 400 µg/kg/day did not exhibit more licking. No other behavioral category was affected by BPA in these dams.
The quantitative stereological analysis of the prefrontal cortex revealed that there were significant increases in the number of both neurons and glia in male rats exposed to 400 µg/kg/day of BPA perinatally compared to unexposed controls. No effects were found in exposed female rats. There is a report of an increase in the number of neurons in the prefrontal cortex of male children with autism (Courchesne, et al., 2011), which may indicate that prenatal exposure to BPA is a predisposing factor for this syndrome.
The results from the radial maze, on the other hand, revealed only minor impairments late in training in male rats exposed to the 40 µg/kg/day dose of BPA. Female performance was not significantly affected. It appears that this cognitive task does not reflect the effects of BPA on the number of neurons. Given the nature of the neural results, more emotional/social tasks might yield effects of pre/perinatal exposure. The experiments examining exposure to BPA during the pubertal period are underway. Preliminary results from the radial arm maze indicate only modest effects of BPA exposure. The neural quantification has just been started and there are no results to report at this time.
Future Activities:
The final cohort of rats that were exposed to BPA during puberty will be run on the radial arm maze in adulthood. Their brains then will be harvested, and the stereological analysis of the number of neurons and glia in the prefrontal cortex will occur in this cohort as well as in the previous cohorts. A graduate student, Leslie Wise, has been trained to perform this analysis but she has not yet begun to gather data. Given prior work from our laboratory that ovarian hormones decrease the number of neurons in the prefrontal cortex, the estrogenic properties of BPA should alter the final number of neurons in this area.
References:
Courchesne, E., Mouton, P., Calhoun, M., Semendeferi, K., Ahrens-Barbeau, C., & Hallet, M. et al. (2011). Neuron Number and Size in Prefrontal Cortex of Children With Autism. JAMA, 306(18), 2001. doi:10.1001/jama.2011.1638
Journal Articles:
No journal articles submitted with this report: View all 7 publications for this subprojectSupplemental Keywords:
BPA, perinatal, adolescence, cognition, neuron number, prefrontal cortex, RFA, Health, Scientific Discipline, Health Risk Assessment, Risk Assessments, Biochemistry, Children's Health, children's vulnerablity, biological markers, developmental disordersRelevant Websites:
Children's Environmental Health Research Center at Illinois
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834593 Water Innovation Network for Sustainable Small Systems Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834593C001 Prenatal Exposure to BPA/Phthalates: Infant Physical and Behavioral Development
R834593C002 Adolescent Exposure to BPA/Phthalates Cognitive and Behavioral Development
R834593C003 Mechanisms of In Utero BPA Exposure on Fetal Gonad Development
R834593C004 Effects of Bisphenol A on the Developing Cortex
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
Main Center: R834593
35 publications for this center
9 journal articles for this center