The vasculature of the paraventricular nucleus of the hypothalamus: influence of development, gamma-aminobutyric acid (GABA) receptors, and prenatal glucocorticoids
Date
2014
Authors
Frahm, Krystle A., author
Tobet, Stuart A., advisor
Hentges, Shane, committee member
Tamkun, Michael, committee member
Garrity, Deborah, committee member
Journal Title
Journal ISSN
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Abstract
The paraventricular nucleus of the hypothalamus (PVN) is a critical brain region that regulates many homeostatic and stress responses. In addition to its dense cytoarchitecture, it also contains a vast network of blood vessels. These blood vessels within the mouse PVN have a higher density than other brain regions, which develops postnatally. Loss of gamma aminobutyric acid (GABA) signaling or prenatal dexamethasone (dex) treatment decreased the blood vessel density. Dex also decreased blood brain barrier (BBB) competency while increasing desmin-immunoreactive pericytes at postnatal day (P)20. Long-term consequences included a decrease in GFAP contact with blood vessels selectively in dex-treated females, and an increase in depression-like behaviors in dex-treated males. Chapter 2 examines the blood vessel density within the PVN. Initially the blood vessel density is similar than surrounding brain regions, then after P8 there was an increase that resulted in a highly vascularized network around P20. The highest densities were restricted to the rostral and mid regions of the PVN, where the neuroendocrine neurons are housed. In addition, mice lacking a functional GABAB receptor had a significant decrease in blood vessel density in the mid region at P20. The protein endocan has been proposed to be a "tip cell" marker, indicating angiogenesis. To further characterize the postnatal angiogenic period within the PVN, recently developed antibodies against endocan were used. Chapter 3 provides evidence that endocan is normally expressed in the mouse brain but not restricted to tip cells. In addition, prior perfusion with fluorescein isothiocyanate (FITC) prevents endocan-immunoreactivity (ir) and provides a novel method for identifying non-functional blood vessels. Chapters 4 and 5 show that excess fetal glucocorticoids alters the BBB within the PVN at two time points. At P20, there was a loss of BBB integrity accompanied by an increase in desmin-ir pericytes on a reduced blood vessel network due to dex-treatment for both prepubertal males and females. In contrast at P50, the blood vessel density and BBB were no longer disrupted following fetal dex-treatment. However, there was a decrease in glial fibrillary acidic protein (GFAP)-ir astrocytes in dex-treated females and an increase in desmin-ir pericytes in dextreated males. In conclusion, the work set forth in this dissertation indicates that the dense vascular network within the PVN develops postnatally and is susceptible to regulation by both exogenous and endogenous factors.
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Subject
paraventricular nucleus of the hypothalamus
blood-brain barrier
glucocorticoids