Different vascular permeability between the sensory and secretory circumventricular organs of adult mouse brain

Morita, Shoko; Miyata, Seiji

doi:10.1007/s00441-012-1421-9

Cited by 92 publications

(132 citation statements)

References 63 publications

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…Fenestrated capillaries are present in the median eminence, a circumventricular organ, and considerable vascular permeability is observed in the arcuate nucleus (36)(37)(38).…”

Section: Expression Of Socs3 In Agrp Neurons Is Dynamically Modulated Inmentioning

confidence: 99%

Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance

Olofsson

Unger

Cheung

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

111

View full text Add to dashboard Cite

Chronic consumption of a fat-rich diet leads to attenuation of leptin signaling in hypothalamic neurons, a hallmark feature of cellular leptin resistance. To date, little is known about the temporal and spatial dysregulation of neuronal function under conditions of nutrient excess. We show that agouti-related protein (AgRP)-expressing neurons precede proopiomelanocortin neurons in developing diet-induced cellular leptin resistance. High-fat diet-induced up-regulation of suppressor of cytokine signaling-3 (SOCS3) occurs in AgRP neurons before proopiomelanocortin and other hypothalamic neurons. SOCS3 expression in AgRP neurons increases after 2 d of high-fat feeding, but reduces after switching to a low-fat diet for 1 d. Consistently, transgenic overexpression of SOCS3 in AgRP neurons produces metabolic phenotypes resembling those observed after short-term high-fat feeding. We further show that AgRP neurons are the predominant cell type situated outside the blood-brain barrier in the mediobasal hypothalamus. AgRP neurons are more responsive to low levels of circulating leptin, but they are also more prone to development of leptin resistance in response to a small increase in blood leptin concentrations. Collectively, these results suggest that AgRP neurons are able to sense slight changes in plasma metabolic signals, allowing them to serve as first-line responders to fluctuation of energy intake. Furthermore, modulation of SOCS3 expression in AgRP neurons may play a dynamic and physiological role in metabolic fine tuning in response to short-term changes of nutritional status.M ost common forms of obesity, including diet-induced obesity, are associated with hyperleptinemia and impairment of leptin signaling in hypothalamic neurons, the hallmark feature of cellular leptin resistance. Suppressor of cytokine signaling-3 (SOCS3), a direct transcriptional product of STAT3, is up-regulated in the hypothalamus of diet-induced obese animals (1, 2). Mice with heterozygous mutation of the Socs3 gene, neuronal, or proopiomelanocortin (POMC)-specific deletion of the Socs3 gene are hypersensitive to leptin and resistant to diet-induced obesity (3-5). Conversely, up-regulation of SOCS3 in POMC neurons of chow-fed mice leads to increased body adiposity (6). In addition, wide-spread up-regulation of SOCS3 has been shown to be associated with neuronal inflammation in diet-induced obese animals (7). Thus SOCS3, which is up-regulated in chronic obesity, is commonly thought to play a pathophysiological role in obesity-associated leptin resistance.Multiple neuronal subtypes in several regions of the hypothalamus, including the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and lateral hypothalamic area, have been implicated in the regulation of energy balance and leptin action (8,9). A number of hypothalamic neurons and extrahypothalamic neurons express functional leptin receptor (10, 11). Among these neurons, POMC and agouti-related protein (AgRP) neurons are two key arcuate neuronal subtypes. POMC and AgRP neu...

show abstract

“…Fenestrated capillaries are present in the median eminence, a circumventricular organ, and considerable vascular permeability is observed in the arcuate nucleus (36)(37)(38).…”

Section: Expression Of Socs3 In Agrp Neurons Is Dynamically Modulated Inmentioning

confidence: 99%

Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance

Olofsson

Unger

Cheung

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

111

View full text Add to dashboard Cite

show abstract

“…The vascular structure of the NH is unique, as endothelial cells are surrounded by a large perivascular space consisting of two layers of the basement membrane (Morita & Miyata 2012). Double-labeling immunohistochemistry showed that CD31-positive endothelial cells were covered by a large laminin-positive perivascular space (Fig.…”

Section: Effects Of Vegfr and Pdgfr Signaling Inhibition On Vascular mentioning

confidence: 99%

“…The vasculature of adult brains generally contains the blood-brain barrier (BBB) that consists of endothelial cell sheet and tight junction and prevents free entry of blood-derived bioactive molecules into parenchyma (Engelhardt 2003, Abbott et al 2010, Daneman et al 2010. The neurosecretory brain regions, the NH and ME, have fenestrated vasculature that has been defined as a characteristic of the lack of complete BBB and the direct diffusion of neuropeptides into blood circulation (Ciofi et al 2009, Miyata & Morita 2011, Mullier et al 2010, Morita & Miyata 2012.…”

Section: Introductionmentioning

confidence: 99%

“…Thus far, little or no attention has been given to the point for elucidating the fundamental vascular characteristic in neurosecretory brain regions, except that they lack most of the tight junction proteins and thereby possess a fenestrated feature (Norsted et al 2008, Mullier et al 2010, Ciofi et al 2009, 2011, Morita & Miyata 2012. However, we have recently shown the occurrence of vascular endothelial growth factor (VEGF)-dependent continuous angiogenesis and the expression of angiogenesis-associated proteins in the ME of adult mice .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the neurohypophysis of adult mice

Furube¹,

Mannari²,

Morita³

et al. 2014

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Hypothalamo-neurohypophysial system (HNS) releases arginine vasopressin (AVP) and oxytocin (OXT) from axonal terminals of the neurohypophysis (NH) into blood circulation for controlling body fluid homeostasis and lactation. Chronic osmotic and suckling stimulations have been shown to cause neurovascular and neuroglial reconstruction in the NH of adult mammals and no study has been reported for vascular dynamics. The aim of this study was to elucidate the occurrence of continuous angiogenesis and growth factor-dependent neurovascular reconstruction in the NH of adult mice. Active proliferation of endothelial cells and oligodendrocyte progenitor cells (OPCs) was observed using the immunohistochemistry of bromodeoxyuridine and Ki-67. Vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2 (KDR)) were highly expressed at pituicytes and endothelial cells respectively. Moreover, prominent expression of platelet-derived growth factor B (PDGFB) and PDGF receptor beta was observed at OXT-containing axonal terminals and pericytes respectively. Administration of the selective tyrosine kinase inhibitor AZD2171 for VEGFRs and STI571 for PDGFRs significantly decreased proliferation of endothelial cells and OPCs. Moreover, AZD2171 treatment decreased vascular density by facilitating apoptosis of endothelial cells and the withdrawal of its treatment led to remarkable rebound proliferation of endothelial cells, so that vascular density rapidly returned to normal levels. AZD2171 decreased the density of both AVP-and OXT-containing axonal terminals, whereas STI571 selectively decreased the density of AVP-containing ones. Thus, this study demonstrates that the signaling pathways of VEGF and PDGF are crucial mediators for determining proliferation of endothelial cells and OPCs and the density of AVP-and OXT-containing axonal terminals in the HNS.

show abstract

“…The most fascinating part of the vascular morphology in CVOs is the capillary vessels having fenestrated endothelial cells in all CVOs aside from the SCO (10) . Thus, the blood-brain barrier (BBB) is lacking in all except one: the SCO and, unlike many regions of the brain, there can be bidirectional movement of polar particles between the blood and the neural environments of the CVOs.…”

Section: Introductionmentioning

confidence: 99%

Localization of Tight Junctions Between Tanycyte-Like Cells of the Sulcus Medianus Organum in Rat Brain

2017

IJMS

View full text Add to dashboard Cite

show abstract

Different vascular permeability between the sensory and secretory circumventricular organs of adult mouse brain

Cited by 92 publications

References 63 publications

Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance

Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance

VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the neurohypophysis of adult mice

Localization of Tight Junctions Between Tanycyte-Like Cells of the Sulcus Medianus Organum in Rat Brain

Contact Info

Product

Resources

About