FP03-4 Prenatal Dexamethasone Impacts Blood Vessel Density and Blood-Brain Barrier Competency Within the Paraventricular Nucleus of the Hypothalamus

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP03-Glucocorticoids & Glucocorticoid Actions
Basic/Translational
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:15 AM
Room 130 (Moscone Center)

Poster Board SAT-5
Krystle anne Frahm*1 and Stuart Allen Tobet2
1colorado state university, fort collins, CO, 2CO State Univ, Fort Collins, CO
The Paraventricular Nucleus of the Hypothalamus (PVN) is a dense collection of neurons that play key roles in maintaining homeostasis and initiating stress responses. It is also characterized by a dense matrix of blood vessels compared to surrounding brain regions. Glucocorticoids have been shown to alter the neural circuitry of the hypothalamic-pituitary-adrenal axis that includes the PVN, but whether blood vessel density or the blood-brain barrier (BBB) are also impacted is unknown. The current study investigated whether glucocorticoid signaling regulates the development of the unique vasculature within the PVN. We focused on BBB permeability and pericytes as an important cellular component of a functional BBB. Pregnant mice on an FVB background were injected with 0.1mg/kg/day of dexamethasone or vehicle during embryonic days (E) 11-17 when there is major neuronal development of the PVN (McClellan et al., 2010). On P20, brains were immersion fixed in 4% paraformaldehyde and vascular endothelial cells were visualized by immunoreactive platelet endothelial cell adhesion molecule (PECAM) to determine blood vessel density. Alternatively, mice were perfused transcardially with heparin PBS containing fluorescein isothiocyanate (FITC) followed by 4% paraformaldehyde to view a compromised BBB for extravascular leakage. For changes in BBB composition, we examined immunoreactive desmin, an intermediate filament in pericytes. Results showed significant decreases in blood vessel length and total immunoreactivity in fetal dex- compared to vehicle-treated mice across the entire PVN and in the rostral and mid PVN regions particularly. For branch points, there was a significant decrease in the rostral and mid regions of the PVN in dex-treated compared to vehicle-treated mice. To investigate BBB competency, leakage of FITC from the perfused vasculature was determined following confocal microscopy. There was PVN-specific increased leakage in the mid region for dex-treated compared to vehicle-treated mice (p < 0.05), corroborated by increased desmin-immunoreactivity (p < 0.05). There was also a strong trend (p < 0.09) for an increase in FITC leakage in the rostral PVN due to dex treatment. Alterations in the vasculature of the PVN may impair neuronal function just as neuron specific alterations would. In general, alterations in the functioning of neurovascular units may provide a novel mechanism for fetal antecedent programming that may influence adult disorder.

Nothing to Disclose: KAF, SAT

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