Leptin Receptor Expression in Mouse Intracranial Perivascular Cells
Past studies have suggested that non-neuronal brain cells express the leptin receptor. However, the identity and distribution of these leptin receptor-expressing non-neuronal brain cells remain debated. This study assessed the distribution of the long form of the leptin receptor (LepRb) in non-neuro...
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doaj-e37bf05c15fc49978097bb99dca13a132020-11-24T20:58:07ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292018-01-011210.3389/fnana.2018.00004327785Leptin Receptor Expression in Mouse Intracranial Perivascular CellsXuefeng Yuan0Xuefeng Yuan1Alexandre Caron2Hua Wu3Laurent Gautron4Division of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDivision of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDivision of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, United StatesPast studies have suggested that non-neuronal brain cells express the leptin receptor. However, the identity and distribution of these leptin receptor-expressing non-neuronal brain cells remain debated. This study assessed the distribution of the long form of the leptin receptor (LepRb) in non-neuronal brain cells using a reporter mouse model in which LepRb-expressing cells are permanently marked by tdTomato fluorescent protein (LepRb-CretdTomato). Double immunohistochemistry revealed that, in agreement with the literature, the vast majority of tdTomato-tagged cells across the mouse brain were neurons (i.e., based on immunoreactivity for NeuN). Non-neuronal structures also contained tdTomato-positive cells, including the choroid plexus and the perivascular space of the meninges and, to a lesser extent, the brain. Based on morphological criteria and immunohistochemistry, perivascular cells were deduced to be mainly pericytes. Notably, tdTomato-positive cells were immunoreactive for vitronectin and platelet derived growth factor receptor beta (PDGFBR). In situ hybridization studies confirmed that most tdTomato-tagged perivascular cells were enriched in leptin receptor mRNA (all isoforms). Using qPCR studies, we confirmed that the mouse meninges were enriched in Leprb and, to a greater extent, the short isoforms of the leptin receptor. Interestingly, qPCR studies further demonstrated significantly altered expression for Vtn and Pdgfrb in the meninges and hypothalamus of LepRb-deficient mice. Collectively, our data demonstrate that the only intracranial non-neuronal cells that express LepRb in the adult mouse are cells that form the blood-brain barrier, including, most notably, meningeal perivascular cells. Our data suggest that pericytic leptin signaling plays a role in the integrity of the intracranial perivascular space and, consequently, may provide a link between obesity and numerous brain diseases.http://journal.frontiersin.org/article/10.3389/fnana.2018.00004/fulladipokinesneuroanatomypericytessignalingtransgenic mice |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuefeng Yuan Xuefeng Yuan Alexandre Caron Hua Wu Laurent Gautron |
spellingShingle |
Xuefeng Yuan Xuefeng Yuan Alexandre Caron Hua Wu Laurent Gautron Leptin Receptor Expression in Mouse Intracranial Perivascular Cells Frontiers in Neuroanatomy adipokines neuroanatomy pericytes signaling transgenic mice |
author_facet |
Xuefeng Yuan Xuefeng Yuan Alexandre Caron Hua Wu Laurent Gautron |
author_sort |
Xuefeng Yuan |
title |
Leptin Receptor Expression in Mouse Intracranial Perivascular Cells |
title_short |
Leptin Receptor Expression in Mouse Intracranial Perivascular Cells |
title_full |
Leptin Receptor Expression in Mouse Intracranial Perivascular Cells |
title_fullStr |
Leptin Receptor Expression in Mouse Intracranial Perivascular Cells |
title_full_unstemmed |
Leptin Receptor Expression in Mouse Intracranial Perivascular Cells |
title_sort |
leptin receptor expression in mouse intracranial perivascular cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroanatomy |
issn |
1662-5129 |
publishDate |
2018-01-01 |
description |
Past studies have suggested that non-neuronal brain cells express the leptin receptor. However, the identity and distribution of these leptin receptor-expressing non-neuronal brain cells remain debated. This study assessed the distribution of the long form of the leptin receptor (LepRb) in non-neuronal brain cells using a reporter mouse model in which LepRb-expressing cells are permanently marked by tdTomato fluorescent protein (LepRb-CretdTomato). Double immunohistochemistry revealed that, in agreement with the literature, the vast majority of tdTomato-tagged cells across the mouse brain were neurons (i.e., based on immunoreactivity for NeuN). Non-neuronal structures also contained tdTomato-positive cells, including the choroid plexus and the perivascular space of the meninges and, to a lesser extent, the brain. Based on morphological criteria and immunohistochemistry, perivascular cells were deduced to be mainly pericytes. Notably, tdTomato-positive cells were immunoreactive for vitronectin and platelet derived growth factor receptor beta (PDGFBR). In situ hybridization studies confirmed that most tdTomato-tagged perivascular cells were enriched in leptin receptor mRNA (all isoforms). Using qPCR studies, we confirmed that the mouse meninges were enriched in Leprb and, to a greater extent, the short isoforms of the leptin receptor. Interestingly, qPCR studies further demonstrated significantly altered expression for Vtn and Pdgfrb in the meninges and hypothalamus of LepRb-deficient mice. Collectively, our data demonstrate that the only intracranial non-neuronal cells that express LepRb in the adult mouse are cells that form the blood-brain barrier, including, most notably, meningeal perivascular cells. Our data suggest that pericytic leptin signaling plays a role in the integrity of the intracranial perivascular space and, consequently, may provide a link between obesity and numerous brain diseases. |
topic |
adipokines neuroanatomy pericytes signaling transgenic mice |
url |
http://journal.frontiersin.org/article/10.3389/fnana.2018.00004/full |
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