The Sex-Specific Developmental Effects of Flame Retardants on White Matter

1. The Sex-Specific Developmental Effects of Flame Retardants on White Matter Anna Cotroneo Columbia High School Dr. Veronica Miller,Dr. Richard F. Seegal Wadsworth Center

2. The Facts • Since WWI, 80,000 new chemical compounds have been developed • Over 3,000 have a production value over one million pounds per year • Less then 20% of these have been tested for toxicity • Present in everyday objects found in homes, schools, and communities • Infants and children are most susceptible to toxic affects • Lack of protective structure (blood brain barrier) • Greater risk of exposure

3. Structure PCBs PBDEs

4. Why PBDEs?

5. Where are PBDEs Found? • Studies show that PBDEs are present in serum of North American residents at 10 to 40 times higher levels then people in Japan or Europe. • Found in electronics, wire insulations, clothes and furniture foams. • PBDEs are and persist in the environment and in the fat of organisms bodies • Use Banned in eight states • Still exposed through the millions of pounds present in consumer products.

6. Exposure

7. Age, sex, genetic, dietary, environmental, immune and endocrine factors. ADHD/ Autism Dementia Risk Of Disease 0-4yrs >60yrs Age Pre/Post-natal Exposure • In Utero the fetus is exposed through the placenta • Post-natally the baby is exposed through breast milk • Lack of protective structures within the developing brain.

8. ADHD • More than one million children in the United States have been diagnosed with this disorder • Anywhere from four times to nine times more prevalent in boys than in girls.

9. Sex Differences in ADHD Boys Girls • distracted, untidy, or late with assignments. • They frequently are accused of not listening. • usually don’t disrupt class or prompt parent-teacher conferences. • inability to sit still when sitting still is required, • a tendency to blurt out in class, • and poor impulse control that hurts relationships at school and home. Hyperactivity/impulsivity Type ADHD Inattentive Type ADHD

10. Not all boys get ADHD Risk Factors. Sex. Toxicants. Infections. Genetics. Hormones. Genetics. Immune.

11. The Cerebellum • The cerebellum influences coordination and also plays a role in a person's attention span and ability to process things like language and music. • Made up of white matter

12. White Matter • White fatty substance through which messages are passed via insulated axons. • White Matter is made up of astrocytes and oligodendrocytes. • When white matter is depleted messages cannot move as efficiently from cell to cell.

13. OPC T4 Oligodendrocyte Astrocytes Immune cells that perform tasks such as transmitter reuptake and release, modulation of synaptic transmission, and the promotion of myelinating activity and nervous system repair. Cells that insulate axons and allow for the movement of signals throughout the brain

14. Thyroid Hormone and PBDEs T4 PBDEs • PBDEs affect TH levels in three major ways • Mimicking the TH and affecting synthesis • Interfere with TH carrier proteins • interfere with liver excretion • Affect the hypothalamus-pituitary-thyroid axis

15. Review of Literature Mount Sinani Childrens Enviornmental Heath Center. Protecting Children against Enviornmetal Threats to Health. New York, NY: Mount Sinani Childrens Health Center, 2010. Print. • The danger of childhood expsore PBDEs Pollutuion and Prevention(OPPTS) US EPA. “US environnmental protection Agency. • The Prevalence of PBDEs in the environment • Miller, Veronica “DEvelopmetnal PCB Exposure Induces HYpothyroxinemia and Sex-specific effects on cerebellum Glial Protein levels. International journal of Developmental Neurosciecne • Connected the effects with ADHD

16. Hypothesis Maternal Exposure to PBDEs will sex-specifically decrease white matter and levels in developing rat brains

17. Methods Pregnant Long Evans Dams were exposed to either a control (corn oil) or high (34.2mg/kg/day) dose of PBDE-71. The fetuses were exposed from gestational day 6 until post-natal day 21. (first 21 days of a rats life is equal to the third trimester) PBDE Exposure Pups were sacrificed at Post-natal day 7, 14, 21, 42 n=4 per group

18. Thyroid Hormone • Circulating Serum Thyroid Hormones were measured using HPLC. I was not involved in this procedure T4 levels • PBDEs like PCBs decrease the amount of circulating TH in the brain. No differences between sexes.

19. IHC and ELISA • Block • Primary • Secondary • HRP • DAB

20. IHC vs ELISA • Immunohistochemistry is region specific because it is tested within the tissue prepared by sectioning half brain paraffin embedded tissue. • ELISAs are homogenates meaning that it is sonicated brain tissue. It is a procedure completed in wells.

21. Analysis • LED microscope • Image J software • Measure density • SPSS

22. MBP ELISA IHC * *

23. GFAP ELISA * * * *

24. Results • Males • The effects in the males are significant. • Gain MBP (Oligo) • Lose GFAP (astrocytes) • Both • Have a decrease in TH • Females higher then male controls • Females • No affects of MBP or GFAP after treatment with PBDEs Females

25. Conclusion • In conclusion we have found that • There is not a sex difference present in the levels of TH • There is a sex difference in the density of white matter after treatment with PBDEs in the cerebellum in MBP and GFAP • Originally there is a sex-difference in the control animals

26. Future Research • To look at the mechanics between the production of TH and the eventual ending of white matter to see what is causing the difference in white matter growth • I would like to look at Deiodinase type 3 because it is the enzyme that changes T4 to the active form T3

27. Acknowledgements • Dr Richard Seegal • Dr. Veronica Miller • Nicole Neu, Bob Sicko • Ms Gleason and Ms Strauss • The other science research students

28. References Developmental neurotoxcity of PBDEs, Nova Science Publisher, 2010 Ahmed, o. A. ELgareij, A . Elbakry S. Abdesltawab “Thyroid hoemones states ans brain development interactions” ONternational Journal of Development Neuroscience 26.2 (2008):147-209. print KandelEric R., James H,. Schwarts and thomas M Jessel. Princples of neural Science. New Touek: Mcgraw-Hill< Health Professions Divison, 2000. Print Mount Sinani Childrens Enviornmental Heath Center. Protecting Children against Enviornmetal Threats to Health. New York, NY: Mount Sinani Childrens Health Center, 2010. Print. PBDEs Pollutuion and Prevention(OPPTS) US EPA. “US environnmental protection Agency.