| Government of Ontario/R.
Howard Webster Foundation/Genesis Research Foundation/Physiology
Graduate Scholarship in Science and Technology at the
University of Toronto.
Thesis: The Effects of Prenatal Stress and Glucocorticoid
Exposure on Hippocampal Long-term Potentiation (MSc.)
Glucocorticoids (GC) such as
cortisol are the main product of the stress response.
Additionally, synthetic GCs (sGCs) are routinely used
to treat pregnant women at risk of preterm labour. This
results in elevated levels of glucocorticoids to the
fetus during pregnancy.
Studies have shown maternal stress
or maternal treatment with sGCs during late gestation
has a permanent effect on the stress response in the
fetus, as well as in neonatal and adult offspring. However,
the consequence for cognitive development of the offspring
remains uncertain. Studies have shown a higher incidence
of neurodevelopmental abnormalities in children exposed
in utero or treated neonatally with glucocorticoids.
Neonatal treatment with glucocorticoids
results in deficits in spatial learning and memory.
It has also been shown that with this neonatal treatement,
long-term potentiation (LTP) in the CA1 subfield of
the hippocampus is impaired. Long-term potentiation
(LTP), a form of synaptic plasticity involving the strengthening
of the post-synaptic response in frequently used synapses,
is likely the mechanism underlying learning and memory.
LTP in CA1 is dependent on the glutamatergic NMDA receptor
and plasticity in this subfield has been correlated
with spatial learning and memory.
Further, studies have demonstrated
bidirectional effects of glucocorticoid (GR) and mineralocorticoid
(MR) receptor activation on LTP. The Matthews lab has
recently shown that prenatal exposure to betamethasone,
the preferred sGC in North America, can modulate NMDA-R
subunit expression in a sex-specific and time-dependent
fashion in the fetus. Additionally, animals treated
with betamethasone show impaired performance in relearning
in the Morris water maze, a test of spatial learning.
Currently nothing is known about the effects of prenatal
GC exposure on synaptic plasticity of the offspring,
though data indicates that there may be detrimental
effects if exposure occurs during key times in neurodevelopment.
Hypothesis: Prenatal
exposure to glucocorticoids will have an adverse effect
on long-term potentiation in the juvenile guinea pig
hippocampus. Further, altered trajectory of GR and MR
expression will produce changes in the postnatal response
to GC and subsequent GR/MR-dependent modulation of LTP.
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