| dc.description.abstract |
<p>Altered dietary availability of the vital nutrient choline during early development
leads to persistent changes in brain and behavior throughout adulthood. Prenatal choline
supplementation during embryonic days (ED) 12-17 of the rodent gestation period enhances
memory capacity and precision and hippocampal plasticity in adulthood, and protects
against spatial learning and memory deficits shortly after excitotoxic seizures, whereas
prenatal choline deficiency can compromise hippocampal memory and plasticity in adulthood.
Recent evidence from our laboratory has determined that lifelong proliferation of
newborn neurons in the adult hippocampus, a feature of adult hippocampal plasticity
that has been implicated in some aspects of learning and memory, is modulated by early
choline availability. Prenatal choline's effects on adult neurogenesis may be one
mechanism for diet-induced cognitive changes throughout life and in response to injury,
although little is known about the mechanisms underlying how prenatal choline alters
adult neurogenesis or the neural mechanisms underlying prenatal choline supplementation's
protection against cognitive deficits after seizures. To address these issues, the
present set of experiments investigated how prenatal choline availability modulates
specific properties of neurogenesis in the adult brain (in the intact brain and in
response to injury), as well as hippocampal markers known to change in response to
excitotoxin-induced seizures, and sought to relate changes in neurogenesis and in
neuropathological markers following injury to changes in performance on spatial learning
and memory tasks. Subjects in each experiment were adult offspring from rat dams that
received either a control diet or diet supplemented with choline chloride or deficient
of choline on ED 12-17. To measure neurogenesis, rats were given injections of the
mitotic marker bromodeoxyurdine to label dividing cells in the hippocampus. Prenatal
choline supplementation enhanced several properties of basal adult hippocampal neurogenesis
(cell division and survival, neural stem/progenitor cell phenotype and proliferative
capacity, trophic support), and this increase was associated with improvements in
spatial working memory retention in a delayed-matching-to-place water maze task. In
contrast, prenatal choline deficiency had little effect on basal adult hippocampal
neurogenesis, and no effect on spatial memory performance. Prenatal choline supplementation
also enhanced olfactory bulb neurogenesis without altering cell proliferation in the
subventricular zone, while prenatal choline deficiency had no effect on either measure,
showing for the first time that prenatal choline's effects on adult neurogenesis is
similarly expressed in another distinct neurogenic region of the adult brain. Altered
prenatal choline availability also modulated the hippocampal response to kainic acid-induced
seizures where supplementation attenuated while deficiency had no effect on the injury-induced
proliferative response of the dentate gyrus shortly after injury. Prenatal choline
supplementation also attenuated other markers of hippocampal neuropathology shortly
after seizures and promoted the long-term hippocampal recovery from seizures months
after injury, including rescuing declines in adult hippocampal neurogenesis and in
spatial memory performance in a standard water maze task. Taken together, these findings
demonstrate a robust neuroprotective effect of prenatal choline supplementation that
may be driven by enhanced adult hippocampal plasticity and trophic support prior to
injury, and shed light on the mechanisms underlying how prenatal choline availability
alters adult hippocampal neurogenesis, which may contribute to changes in memory capacity
and precision both throughout life and following neural assault.</p>
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