Diapositive 1 - Cisbio Bioassays
Diapositive 1 - Cisbio Bioassays
Diapositive 1 - Cisbio Bioassays
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Tanycytes as gatekeepers of the<br />
Metabolic Brain<br />
Vincent Prevot<br />
Inserm team “ Development and Plasticity of the Postnatal<br />
Brain” Jean-Pierre Aubert Research Centre, U837, Lille<br />
France
Metabolic signals and energy homeostasis<br />
CNS:<br />
hypothalamus<br />
Ghrelin<br />
Leptin<br />
Stomach<br />
Adipocytes
Metabolic signals and energy homeostasis<br />
P12<br />
Reduce/promote<br />
food intake<br />
Increase energy<br />
expenditure<br />
P12<br />
NPY/AgRP<br />
POMC/CART<br />
Ghrelin<br />
Leptin<br />
Stomach<br />
Adipocytes
Do circulating metabolic signals have direct access to the arcuate nucleus<br />
of the hypothalamus (ARH)?<br />
DMH<br />
VMH<br />
ARH<br />
Circulating<br />
metabolic<br />
signals<br />
Tanycytic<br />
processes<br />
3V<br />
Median<br />
Eminence
Do circulating metabolic signals have direct access to the arcuate nucleus<br />
of the hypothalamus (ARH)?<br />
DMH<br />
VMH<br />
ARH<br />
Circulating<br />
metabolic<br />
signals<br />
Tanycytic<br />
processes<br />
3V<br />
Tight junctions<br />
Median<br />
Eminence
Do circulating metabolic signals have direct access to the arcuate nucleus<br />
of the hypothalamus (ARH)?<br />
DMH<br />
VMH<br />
ARH<br />
Circulating<br />
metabolic<br />
signals<br />
Tanycytic<br />
processes<br />
Fenestrated blood vessels<br />
3V<br />
Tight junctions<br />
Median<br />
Eminence
Do circulating metabolic signals have direct access to the arcuate nucleus<br />
of the hypothalamus (ARH)?<br />
Nerve Terminal<br />
DMH<br />
Endothelial cell<br />
nucleus<br />
VMH<br />
ARH<br />
3V<br />
Tight junctions<br />
Tanycytic<br />
processes<br />
Fenestrated blood vessels<br />
Median<br />
Eminence
Median eminence fenestrated capillaries are permeable to circulating<br />
metabolic signals<br />
Nerve Terminal<br />
Endothelial cell<br />
nucleus<br />
Schaeffer et al, PNAS 110: 1512-1517, 2013
Median eminence fenestrated capillaries are permeable to circulating metabolic<br />
signals, however, …<br />
Intravenous infusion<br />
of an inert dye<br />
e.g., Evans blue (1 kDa)<br />
DMH<br />
VMH<br />
Tight junctions<br />
ARH<br />
3V<br />
Median<br />
Eminence<br />
Fenestrated blood vessels
Median eminence fenestrated capillaries are permeable to circulating metabolic<br />
signals, however, their diffusion appears to be restricted to the median eminence<br />
Intravenous infusion<br />
of an inert dye<br />
e.g., Evans blue (1 kDa)<br />
DMH<br />
VMH<br />
ARH<br />
3V<br />
Median<br />
Eminence<br />
Mullier et al, J Comp Neurol 518:943, 2010
Does nutritional status regulate this blood-hypothalamus barrier composed of<br />
tanycytes and fenestrated endothelial cells ?
Fasting induces Plasticity of the Blood-Hypothalamus Barrier<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Fasting induces Plasticity of the Blood-Hypothalamus Barrier<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Glucose deprivation mediates Fasting-induced Plasticity at the Blood-<br />
Hypothalamus Barrier<br />
Fenestrated vessels in the ARH<br />
Organized tight junctions in ARH tanycytes<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Fasting and Glucoprivation require VEGF Signaling to promote Plasticity at the<br />
Blood-Hypothalamus Barrier<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Fasting requires VEGF-A expression in tanycytes to promote Plasticity at the<br />
Blood-Hypothalamus Barrier<br />
Fenestrated vessels in the ARH<br />
Organized tight junctions in ARH tanycytes<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Do Tanycytes, which were recently shown to be Glucosensing Cells play a dynamic<br />
role in Fasting-induced Brain-Hypothalamus Barrier Plasticity?<br />
Bolborea and Dale, TINS, 36:91-100, 2012
TAT-Cre recombinant protein infusion into the third ventricle selectively targets<br />
tanycytes<br />
tat-Cre intracerebrobentricular infusion in tdTomato loxP/+ mice<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Real time-PCR analysis of gene expression in tanycytes in vivo<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Fasting promotes VEGF-A expression in tanycytes<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Fasting-induced Blood-Hypothalamus Barrier Plasticity Requires Tanycytic VEGF-A<br />
expression<br />
Fenestrated vessels in the ARH<br />
Organized tight junctions in ARH tanycytes<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Blood-Hypothalamus Barrier Plasticity Modulates Access of Blood-Borne Factors<br />
to the ventromedial Arcuate Nucleus (vmARH)<br />
Intravenous injection of Evans blue<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Blood-Hypothalamus Barrier Plasticity Modulates Access of Blood-Borne<br />
metabolic Factors to the ventromedial Arcuate Nucleus (vmARH)<br />
Intravenous injection of fluorescently labeled grhelin<br />
Control Fasting Refeeding<br />
Schaeffer et al, PNAS 110: 1512-1517, 2013
Blood-Hypothalamus Barrier Plasticity Modulates Feeding<br />
Langlet et al., Cell Metab, 17:607-617, 2013
Conclusion<br />
• Fasting induces the plasticity of brain<br />
barriers in hypothalamic feeding regions<br />
• Central neuroglucopenia triggers bloodhypothalamus<br />
barrier plasticity<br />
• Fasting-induced brain barrier plasticity<br />
requires VEGF-A expression in tanycytes<br />
• The tanycytic barrier modulates bloodborne<br />
signals access to CNS feeding<br />
circuits<br />
Mullier et al, J Comp Neurol 518:943, 2010<br />
Langlet et al., Cell Metab, 17:607-617, 2013<br />
Schaeffer et al, PNAS 110: 1512-1517, 2013
Acknowledgments<br />
Fanny Langlet<br />
Bénédicte Dehouck<br />
Collaborators<br />
<strong>Cisbio</strong> <strong>Bioassays</strong><br />
- Eric Trinquet<br />
IGF, Montpellier<br />
- Patrice Mollard<br />
- Marie Schaeffer<br />
VIB, Leuven, Belgium<br />
-Massimiliano Mazzone<br />
- Peter Carmeliet
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