Faculty Opinions recommendation of Gonadotropin-releasing hormone neurons extend complex highly branched dendritic trees outside the blood-brain barrier.

GnRH neurons project axons to the median eminence to control pituitary release of gonadotropins and, as such, represent the principal output neurons of the neuronal network controlling fertility. It is well established that the GnRH neurons exhibit a simple bipolar morphology with one or two long dendrites. Using adult GnRH-green fluorescent protein transgenic mice and juxtacellular cell filling, we report here that a subpopulation of GnRH neurons located in the rostral preoptic area exhibit extremely complex branching dendritic trees that fill the organum vasculosum of the lamina terminalis (OVLT). The dendritic nature of these processes was demonstrated at both light and electron microscopic levels by the presence of spines, dendritic ultrastructure, and synapses. Further, electrophysiological recordings showed that GnRH neurons were excited by glutamate as well as kisspeptin puffed onto their dendrites located within the OVLT. Using iv injection of horseradish peroxidase, a molecule unable to penetrate the blood-brain barrier (BBB), we show that GnRH neuron cell bodies and dendrites within 100 μm of the OVLT reside outside the BBB. Approximately 85% of GnRH neurons in this area express c-Fos at the time of the GnRH surge. These observations demonstrate that GnRH neurons extend complex, highly branched dendritic trees beyond the BBB into the OVLT, where they will be able to sense directly molecules circulating in the bloodstream. This indicates a new mechanism for the modulation of GnRH neurons that extends considerably the range of factors that are integrated by these neurons for the control of fertility.

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Differential Interactions of Urocortin/Corticotropin-Releasing Hormone Peptides with the Blood-Brain Barrier

Neuroendocrinology ◽

10.1159/000059433 ◽

2002 ◽

Vol 75 (6) ◽

pp. 367-374 ◽

Cited By ~ 35

Author(s):

Abba J. Kastin ◽

Victoria Akerstrom

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Blood Brain

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Corticotropin-Releasing Hormone Receptor-1 in Cerebral Microvessels Changes during Development and Influences Urocortin Transport across the Blood-Brain Barrier

Endocrinology ◽

10.1210/en.2009-1039 ◽

2009 ◽

Vol 151 (3) ◽

pp. 1221-1227 ◽

Cited By ~ 10

Author(s):

Hung Hsuchou ◽

Abba J. Kastin ◽

Xiaojun Wu ◽

Hong Tu ◽

Weihong Pan

Keyword(s):

Blood Brain Barrier ◽

Hormone Receptor ◽

Brain Barrier ◽

Receptor Subtypes ◽

Multiple Time ◽

Corticotropin Releasing Hormone ◽

Cerebral Microvessels ◽

Releasing Hormone ◽

Adult Mice ◽

Blood Brain

In this study we tested the hypothesis that receptor-mediated transport of urocortin across the blood-brain barrier (BBB) undergoes developmental changes. Urocortin is a peptide produced by both selective brain regions and peripheral organs, and it is involved in feeding, memory, mood, cardiovascular functions, and immune regulation. In BBB studies with multiple-time regression analysis, we found that neonatal mice had a significant influx of 125I-urocortin. By contrast, adult mice did not transport urocortin across the BBB. Quantitative RT-PCR showed that corticotropin-releasing hormone receptor (CRHR)-1 was developmentally regulated in enriched cerebral microvessels as well as hypothalamus, being significantly higher in neonatal than adult mice. This change was less dramatic in agouti viable yellow mice, a strain that develops adult-onset obesity. The level of expression of CRHR1 mRNA was 33-fold higher in the microvessels than in hypothalamic homogenates. The mRNA for CRHR2 was less abundant in both regions and less prone to changes with development or the agouti viable yellow mutation. Supported by previous findings of receptor-mediated endocytosis of urocortin, these results suggest that permeation of urocortin across the BBB is dependent on the level of CRHR1 expression in cerebral microvessels. These novel findings of differential regulation of CRH receptor subtypes help elucidate developmental processes in the brain, particularly for the urocortin system.

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