Transcript The Developmental Effects of Flame Retardants on

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
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
Structure
PCBs
PBDEs
Why PBDEs?
Where are PBDEs Found?
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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.
Exposure
Pre/Post-natal Exposure
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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.
ADHD/
Autism
Age, sex, genetic,
dietary,
environmental,
immune and
endocrine
factors.
Dementia
Risk
Of
Disease
0-4yrs
Age
>60yrs
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.
Sex Differences in ADHD
Girls
•
distracted, untidy,
or late with
assignments.
• They frequently are
accused of not
listening.
• usually don’t disrupt
class or prompt
parent-teacher
conferences.
Inattentive Type ADHD
Boys
•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
Not all boys get ADHD
Risk Factors.
Toxicants.
Infections.
Genetics.
Sex.
Hormones.
Genetics.
Immune.
The Cerebellum
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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
White Matter
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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.
OPC
T4
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.
Oligodendrocyte
Cells that insulate axons and
allow for the movement of
signals throughout the brain
Thyroid Hormone and PBDEs
PBDEs
T4
•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
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
Hypothesis
Maternal Exposure to PBDEs will sexspecifically decrease white matter and levels in
developing rat brains
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
•Circulating Serum
Thyroid Hormones
were measured using
HPLC. I was not
involved in this
procedure
•PBDEs like PCBs
decrease the
amount of
circulating TH in
the brain. No
differences between
sexes.
T4 levels
Thyroid Hormone
IHC and ELISA
1. Block
2. Primary
3. Secondary
4. HRP
5. DAB
IHC vs ELISA
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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.
Analysis
•LED microscope
•Image J software
•Measure
density
• SPSS
MBP
ELISA
IHC
Effects of PBDEs at PND21
160
140
120
100
80
60
40
20
0
*
*
140
120
Female Control
Female High
Male Control
Male High
Mean MBP
Mean MBP
Effects of PBDEs at PND21
100
Female Control
80
Female High
60
Male Control
40
Male High
20
0
1
1
Treatment
Treatment
GFAP
ELISA
Effects of PBDEs at PND21
MeanGFAP
250
*
200
*
Female Control
200
Female High
150
Male Control
100
Male High
MeanGFAP
300
Effects of PBDEs at PND21
*
*
150
Female Control
Female High
100
Male Control
Male High
50
50
0
0
1
1
Treatment
Treatment
Results
Females
Females
•No affects of
MBP or GFAP
after treatment
with PBDEs
Both
•Have a
decrease in TH
•Females
higher then
male controls
Males
•The effects in the
males are significant.
•Gain MBP
(Oligo)
•Lose GFAP
(astrocytes)
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
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
Acknowledgements
•Dr Richard Seegal
•Dr. Veronica Miller
•Nicole Neu, Bob Sicko
•Ms Gleason and Ms Strauss
•The other science research students
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.