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Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess.

Frahm KA, Tobet SA - Brain Struct Funct (2014)

Bottom Line: Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20.In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence.Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

View Article: PubMed Central - PubMed

Affiliation: Program in Cell and Molecular Biology, Colorado State University, 1617 Campus Delivery, Fort Collins, CO, 80523-1617, USA.

ABSTRACT
The blood-brain barrier (BBB) is a critical contributor to brain function. To understand its development and potential function in different brain regions, the postnatal (P) BBB was investigated in the mouse cortex (CTX), lateral hypothalamus, and paraventricular nucleus of the hypothalamus (PVN). Brains were examined on postnatal days (P)12, P22 and P52 for BBB competency and for pericytes as key cellular components of the BBB demarcated by immunoreactive desmin. Glucocorticoid influences (excess dexamethasone; dex) during prenatal development were also assessed for their impact on the blood vessels within these regions postnatally. At P12, there was significantly more extravascular leakage of a low molecular weight dye (fluorescein isothiocyanate) in the CTX than within hypothalamic regions. For pericytes, there were low levels of desmin immunoreactivity at P12 that increased with age for all regions. There was more desmin immunoreactivity present in the PVN at each age examined. Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20. In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence. Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

No MeSH data available.


Related in: MedlinePlus

Prenatal exposure to dexamethasone (dex) impacted desmin-immunoreactive pericyte coverage in the mouse paraventricular nucleus of the hypothalamus (PVN) at P20. Example confocal images for each region are provided in panels a–f, and a quantitative summary by graph in g and h. In the PVN, there was a significant increase in desmin-immunoreactive pericyte coverage in dex-treated compared to vehicle-treated mice (c, f; *p < 0.01) when blood vessel density was taken into account (h; *p < 0.01). There were no significant differences observed in desmin-immunoreactive pericyte coverage in the cortex (CTX; a, d) or lateral hypothalamus (LH; b, e) between dex-treated or vehicle-treated mice. There was a significant increase in desmin-immunoreactive pericyte coverage in the PVN regardless of treatment compared to the CTX and LH (g). Number of animals per group is provided in the code for the bars in panels g and h. Significant differences between regions indicated by asterisk and for treatment as hash. Scale bar 50 µm in panel a, which applies to all images
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Fig6: Prenatal exposure to dexamethasone (dex) impacted desmin-immunoreactive pericyte coverage in the mouse paraventricular nucleus of the hypothalamus (PVN) at P20. Example confocal images for each region are provided in panels a–f, and a quantitative summary by graph in g and h. In the PVN, there was a significant increase in desmin-immunoreactive pericyte coverage in dex-treated compared to vehicle-treated mice (c, f; *p < 0.01) when blood vessel density was taken into account (h; *p < 0.01). There were no significant differences observed in desmin-immunoreactive pericyte coverage in the cortex (CTX; a, d) or lateral hypothalamus (LH; b, e) between dex-treated or vehicle-treated mice. There was a significant increase in desmin-immunoreactive pericyte coverage in the PVN regardless of treatment compared to the CTX and LH (g). Number of animals per group is provided in the code for the bars in panels g and h. Significant differences between regions indicated by asterisk and for treatment as hash. Scale bar 50 µm in panel a, which applies to all images

Mentions: To complement and further expand on the extravascular FITC data, desmin-immunoreactive pericyte coverage was assessed. Prenatal dex-treatment led to a significant increase in immunoreactive desmin on a vascular network that was less dense at P20 (Fig. 6). When total desmin immunoreactivity was examined in the PVN, LH or CTX, there were no dex-dependent differences in any region (Fig. 6a–g). However, when blood vessel density was taken into account, there was a significant dex-dependent increase in desmin-immunoreactive pericyte coverage in the mid PVN (Fig. 6h; p < 0.01). There were no significant differences in the rostral or caudal PVN due to treatment. There were also no significant differences in the CTX or LH due to treatment although there was a trend of increased coverage due to dex-treatment for all brain regions examined. Overall, prenatal dex-treated mice increased immunoreactive desmin on blood vessels within the PVN at P20.Fig. 6


Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess.

Frahm KA, Tobet SA - Brain Struct Funct (2014)

Prenatal exposure to dexamethasone (dex) impacted desmin-immunoreactive pericyte coverage in the mouse paraventricular nucleus of the hypothalamus (PVN) at P20. Example confocal images for each region are provided in panels a–f, and a quantitative summary by graph in g and h. In the PVN, there was a significant increase in desmin-immunoreactive pericyte coverage in dex-treated compared to vehicle-treated mice (c, f; *p < 0.01) when blood vessel density was taken into account (h; *p < 0.01). There were no significant differences observed in desmin-immunoreactive pericyte coverage in the cortex (CTX; a, d) or lateral hypothalamus (LH; b, e) between dex-treated or vehicle-treated mice. There was a significant increase in desmin-immunoreactive pericyte coverage in the PVN regardless of treatment compared to the CTX and LH (g). Number of animals per group is provided in the code for the bars in panels g and h. Significant differences between regions indicated by asterisk and for treatment as hash. Scale bar 50 µm in panel a, which applies to all images
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4481307&req=5

Fig6: Prenatal exposure to dexamethasone (dex) impacted desmin-immunoreactive pericyte coverage in the mouse paraventricular nucleus of the hypothalamus (PVN) at P20. Example confocal images for each region are provided in panels a–f, and a quantitative summary by graph in g and h. In the PVN, there was a significant increase in desmin-immunoreactive pericyte coverage in dex-treated compared to vehicle-treated mice (c, f; *p < 0.01) when blood vessel density was taken into account (h; *p < 0.01). There were no significant differences observed in desmin-immunoreactive pericyte coverage in the cortex (CTX; a, d) or lateral hypothalamus (LH; b, e) between dex-treated or vehicle-treated mice. There was a significant increase in desmin-immunoreactive pericyte coverage in the PVN regardless of treatment compared to the CTX and LH (g). Number of animals per group is provided in the code for the bars in panels g and h. Significant differences between regions indicated by asterisk and for treatment as hash. Scale bar 50 µm in panel a, which applies to all images
Mentions: To complement and further expand on the extravascular FITC data, desmin-immunoreactive pericyte coverage was assessed. Prenatal dex-treatment led to a significant increase in immunoreactive desmin on a vascular network that was less dense at P20 (Fig. 6). When total desmin immunoreactivity was examined in the PVN, LH or CTX, there were no dex-dependent differences in any region (Fig. 6a–g). However, when blood vessel density was taken into account, there was a significant dex-dependent increase in desmin-immunoreactive pericyte coverage in the mid PVN (Fig. 6h; p < 0.01). There were no significant differences in the rostral or caudal PVN due to treatment. There were also no significant differences in the CTX or LH due to treatment although there was a trend of increased coverage due to dex-treatment for all brain regions examined. Overall, prenatal dex-treated mice increased immunoreactive desmin on blood vessels within the PVN at P20.Fig. 6

Bottom Line: Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20.In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence.Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

View Article: PubMed Central - PubMed

Affiliation: Program in Cell and Molecular Biology, Colorado State University, 1617 Campus Delivery, Fort Collins, CO, 80523-1617, USA.

ABSTRACT
The blood-brain barrier (BBB) is a critical contributor to brain function. To understand its development and potential function in different brain regions, the postnatal (P) BBB was investigated in the mouse cortex (CTX), lateral hypothalamus, and paraventricular nucleus of the hypothalamus (PVN). Brains were examined on postnatal days (P)12, P22 and P52 for BBB competency and for pericytes as key cellular components of the BBB demarcated by immunoreactive desmin. Glucocorticoid influences (excess dexamethasone; dex) during prenatal development were also assessed for their impact on the blood vessels within these regions postnatally. At P12, there was significantly more extravascular leakage of a low molecular weight dye (fluorescein isothiocyanate) in the CTX than within hypothalamic regions. For pericytes, there were low levels of desmin immunoreactivity at P12 that increased with age for all regions. There was more desmin immunoreactivity present in the PVN at each age examined. Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20. In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence. Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

No MeSH data available.


Related in: MedlinePlus