Browsing by Author "Criss, Kerry"
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Item Behavioral Therapy to Ameliorate the Effects of Neonatal Alcohol Exposure on Dendritic Organization of Pyramidal Neurons in the Rodent mPFC(University of Delaware, 2012-05) Criss, KerryDuring the third trimester of pregnancy in humans, a brain goes through the phase of rapid growth known as “brain growth spurt.” A comparable event in brain development occurs in the first ten postnatal days of a rat’s life. Third trimester alcohol exposure (or its equivalent) results in impaired cognition in adulthood and permanent structural changes in the brain, including the prefrontal cortex. The present study uses a rat model to examine the effect of neonatal alcohol exposure on dendritic morphology of pyramidal neurons in Layer III of the medial prefrontal cortex (mPFC), one of the last brain areas to develop in both humans and rats. Specifically, the density and phenotype of dendritic spines were analyzed. The present study also explores the impact of physical activity (wheel running WR) on dendritic morphology of mPFC neurons. Rat pups were randomly assigned to three groups: intubated with alcohol (5.25 g/kg/day; AE), sham intubated (SI), or suckle controls (SC) on PD 4–9. In order to study the effect of voluntary exercise, animals were placed in cages where they had 24-hour access to wheels during PD30-42. On the final day treatment, rats were anesthetized and perfused with 0.9% saline. Brains were subsequently processed for Golgi-Cox staining. Spine density and spine phenotypes were analyzed for basilar dendrites of Layer III mPFC neurons. The present study found that neonatal exposure to alcohol results in reduced spine density in both proximal and distal branches of basilar dendrites. This outcome was ameliorated following exposure to WR. In contrast, no differences in spine phenotype ratios were observed, but it was found that that regardless of housing and postnatal treatment, proximal branches had significantly more mature spines than distal branches.Item Impact of binge-like alcohol exposure during the third trimester equivalent on cell cycle kinetics of progenitor cells in the dentate gyrus of PD10 rats(University of Delaware, 2013) Criss, KerryThe subgranular zone (SGZ) of the dentate gyrus (DG) is one of two areas of the brain where neurons are generated into adulthood; the other is the subventricular zone. This unique cell population undergoes significant growth during the brain growth spurt (a postnatal event in rodents) and continues to develop throughout the lifespan. Several studies have examined the impact of neonatal alcohol exposure (AE) on postnatal neurogenesis in the developing DG. For example, a significant decrease in the number of granule cells was observed on PD10 in rats that received a daily binge-like dose of alcohol during the third trimester equivalent (PD4-9) or the equivalent of entire human gestation (G1-20 + PD4-9) (1). Furthermore, the impact of developmental AE on these precursors and their progeny is long lasting. Previous work in our lab demonstrated that binge-like AE on PD4-9 did not affect cell proliferation on PD42 or PD50 (2; 3) but decreased the number of adult-born granule cells that matured and survived for 30 days (3). Observed changes in postnatal neurogenesis could possibly reflect an enduring impact of neonatal AE on the progenitors' cell cycle. Indeed, several studies have demonstrated that alcohol alters cell cycle kinetics. For example, a high dose of alcohol in vitro (400 mg/dl) lengthened the cell cycle and increased the incidence of cell death in neocortical cell cultures obtained from rodent fetuses on G16 (4). Prenatal AE lengthened the cell cycle of proliferating cells in the ventricular zone due to an elongation of the G1 phase, while exposure did not impact cell cycle length of cells proliferating in the subventricular zone (5). The current study examined the impact of binge-like AE during the third trimester equivalent on the cell cycle kinetics of neural precursors (NPCs) in the SGZ of DG of the rodent hippocampus. Rat pups were randomly assigned to three groups on PD4: intubated with alcohol (5.25 g/kg/day; AE), shamintubated (SI), or suckle control (SC). Following sacrifice on PD10, cumulative labeling with bromodeoxyuridine (BrdU) was performed. Future work will examine the impact of developmental alcohol exposure on two other cell populations, Sox2+ and Ki67+ cells. Then, the total length of the cell cycle and the S phase can be calculated. This study was undertaken to establish if a change in duration of granule cell precursors' cell cycle at PD10 could be a cellular mechanism leading to alterations in new neuron survival.