From Neurodevelopmental Models to Endocrine Disruption: Metabolomic Insights from In Vitro a nd In Vivo Studies
Chemist Sara Evangelista focused on how endocrine disrupting chemicals (EDCs) can affect early brain dev elopment and contribute to long-term cognitive and behavioral problem s. Early life is a vulnerable period in which hormones, neurotransmit ters, and lipids govern key neurodevelopmental processes, making thes e systems potential targets for chemical disruption.
T o better understand the underlying mechanisms, Evangelista combined r at studies with human cortical brain organoids (CBOs), an emerging mo del that mimics early human brain development. The CBO research provi ded a metabolic and lipidomic reference framework for evaluating the extent to which this model reflects the neurodevelopmental pathways r elevant to toxicity testing. Parallel to this, she investigated how p erinatal exposure to selected EDCs alters metabolic and hormonal path ways in the developing rat hippocampus and whether these early change s are associated with later behavioral deficits. The overarching moti vation was to generate mechanistic insights that would support more p redictive and human-relevant approaches to assessing developmental ne urotoxicity.
Normal Brain Development Can Be Disrupted<
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The research demonstrated that certain chemicals we are e
xposed to daily—known as endocrine disruptors (EDCs)—can disrupt
normal brain development when exposure occurs very early in life. In
rats, Evangelista found that these chemicals altered key molecules in
the developing brain, such as hormones, lipids, and neurotransmitter
s, all of which are necessary for healthy growth. Some of these early
changes were associated with learning and memory problems later in l
ife, demonstrating that early disruption can have lasting consequence
s.
Promising Laboratory Models
Human stem c
ell-derived brain organoids ("mini-brains") have also been shown to d
evelop metabolic characteristics similar to those observed in early h
uman brain development. This means they can serve as promising labora
tory models for studying how chemicals can affect the developing brai
n without relying solely on animal testing. Overall, my work provides
early warning signs and tools to better identify chemicals that can
harm brain development.
More information on the thesis<
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DESCRIPTION: Chemist Sara Evangelista focused on how endocrine
disrupting chemicals (EDCs) can affect early brain development and c
ontribute to long-term cognitive and behavioral problems. Early life
is a vulnerable period in which hormones, neurotransmitters, and lipi
ds govern key neurodevelopmental processes, making these systems pote
ntial targets for chemical disruption. To better understand
the underlying mechanisms, Evangelista combined rat studies with huma
n cortical brain organoids (CBOs), an emerging model that mimics earl
y human brain development. The CBO research provided a metabolic and
lipidomic reference framework for evaluating the extent to which this
model reflects the neurodevelopmental pathways relevant to toxicity
testing. Parallel to this, she investigated how perinatal exposure to
selected EDCs alters metabolic and hormonal pathways in the developi
ng rat hippocampus and whether these early changes are associated wit
h later behavioral deficits. The overarching motivation was to genera
te mechanistic insights that would support more predictive and human-
relevant approaches to assessing developmental neurotoxicity. Normal Brain Development Can Be Disrupted
The research d
emonstrated that certain chemicals we are exposed to daily—known as
endocrine disruptors (EDCs)—can disrupt normal brain development w
hen exposure occurs very early in life. In rats, Evangelista found th
at these chemicals altered key molecules in the developing brain, suc
h as hormones, lipids, and neurotransmitters, all of which are necess
ary for healthy growth. Some of these early changes were associated w
ith learning and memory problems later in life, demonstrating that ea
rly disruption can have lasting consequences. Promising Labor
atory Models
Human stem cell-derived brain organoids ("mi
ni-brains") have also been shown to develop metabolic characteristics
similar to those observed in early human brain development. This mea
ns they can serve as promising laboratory models for studying how che
micals can affect the developing brain without relying solely on anim
al testing. Overall, my work provides early warning signs and tools t
o better identify chemicals that can harm brain development. More inf
ormation on the thesis From Neurodevelopmental Models to Endo
crine Disruption: Metabolomic Insights from In Vitro and In Vivo Stud
ies
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