Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain

Summary: Astrocytes interact with not only synapses but also brain blood vessels through perivascular astrocyte endfeet (PV-AEF) to form the neurovascular unit (NVU). However, PV-AEF components have not been fully identified. Here, we biochemically isolated blood vessels from mouse brain homogenates...

Full description

Bibliographic Details
Main Authors: Takeshi Kameyama, Muneaki Miyata, Hajime Shiotani, Jun Adachi, Soichiro Kakuta, Yasuo Uchiyama, Kiyohito Mizutani, Yoshimi Takai
Format: Article
Language:English
Published: Elsevier 2023-10-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223020874
_version_ 1797647803794587648
author Takeshi Kameyama
Muneaki Miyata
Hajime Shiotani
Jun Adachi
Soichiro Kakuta
Yasuo Uchiyama
Kiyohito Mizutani
Yoshimi Takai
author_facet Takeshi Kameyama
Muneaki Miyata
Hajime Shiotani
Jun Adachi
Soichiro Kakuta
Yasuo Uchiyama
Kiyohito Mizutani
Yoshimi Takai
author_sort Takeshi Kameyama
collection DOAJ
description Summary: Astrocytes interact with not only synapses but also brain blood vessels through perivascular astrocyte endfeet (PV-AEF) to form the neurovascular unit (NVU). However, PV-AEF components have not been fully identified. Here, we biochemically isolated blood vessels from mouse brain homogenates and purified PV-AEF. The purified PV-AEF were observed in different sizes, similar to PV-AEF on brain blood vessels. Mass spectrometry analysis identified 9,762 proteins in the purified PV-AEF, including cell adhesion molecules, nectin-2δ, Kirrel2, and podoplanin. Immunofluorescence microscopic analysis revealed that nectin-2δ and podoplanin were concentrated mainly in arteries/arterioles and veins/venules of the mouse brain, whereas Kirrel2 was mainly in arteries/arterioles. Nectin-2α/δ, Kirrel2, and podoplanin were preferentially observed in large sizes of the purified PV-AEF. Furthermore, Kirrel2 potentially has cell adhesion activity of cultured astrocytes. Collectively, these results indicate that PV-AEF have heterogeneity in sizes and molecular components, implying different roles of PV-AEF in NVU function depending on vascular regions.
first_indexed 2024-03-11T15:21:47Z
format Article
id doaj.art-284f87b094cb43ccba6d8301bf19a4f1
institution Directory Open Access Journal
issn 2589-0042
language English
last_indexed 2024-03-11T15:21:47Z
publishDate 2023-10-01
publisher Elsevier
record_format Article
series iScience
spelling doaj.art-284f87b094cb43ccba6d8301bf19a4f12023-10-28T05:09:17ZengElsevieriScience2589-00422023-10-012610108010Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brainTakeshi Kameyama0Muneaki Miyata1Hajime Shiotani2Jun Adachi3Soichiro Kakuta4Yasuo Uchiyama5Kiyohito Mizutani6Yoshimi Takai7Division of Pathogenetic Signaling, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima 770-8503, JapanDivision of Pathogenetic Signaling, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; Division of Pathogenetic Signaling, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, JapanDivision of Pathogenetic Signaling, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; Division of Pathogenetic Signaling, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, JapanLaboratory of Proteomics for Drug Discovery, Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Clinical and Analytical Chemistry, Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, JapanLaboratory of Morphology and Image Analysis, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Department of Cellular Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Cellular Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanDivision of Pathogenetic Signaling, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; Division of Pathogenetic Signaling, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, Japan; Corresponding authorDivision of Pathogenetic Signaling, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; Corresponding authorSummary: Astrocytes interact with not only synapses but also brain blood vessels through perivascular astrocyte endfeet (PV-AEF) to form the neurovascular unit (NVU). However, PV-AEF components have not been fully identified. Here, we biochemically isolated blood vessels from mouse brain homogenates and purified PV-AEF. The purified PV-AEF were observed in different sizes, similar to PV-AEF on brain blood vessels. Mass spectrometry analysis identified 9,762 proteins in the purified PV-AEF, including cell adhesion molecules, nectin-2δ, Kirrel2, and podoplanin. Immunofluorescence microscopic analysis revealed that nectin-2δ and podoplanin were concentrated mainly in arteries/arterioles and veins/venules of the mouse brain, whereas Kirrel2 was mainly in arteries/arterioles. Nectin-2α/δ, Kirrel2, and podoplanin were preferentially observed in large sizes of the purified PV-AEF. Furthermore, Kirrel2 potentially has cell adhesion activity of cultured astrocytes. Collectively, these results indicate that PV-AEF have heterogeneity in sizes and molecular components, implying different roles of PV-AEF in NVU function depending on vascular regions.http://www.sciencedirect.com/science/article/pii/S2589004223020874Vascular anatomyImmunologyMolecular neuroscience
spellingShingle Takeshi Kameyama
Muneaki Miyata
Hajime Shiotani
Jun Adachi
Soichiro Kakuta
Yasuo Uchiyama
Kiyohito Mizutani
Yoshimi Takai
Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
iScience
Vascular anatomy
Immunology
Molecular neuroscience
title Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
title_full Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
title_fullStr Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
title_full_unstemmed Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
title_short Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
title_sort heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
topic Vascular anatomy
Immunology
Molecular neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004223020874
work_keys_str_mv AT takeshikameyama heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain
AT muneakimiyata heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain
AT hajimeshiotani heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain
AT junadachi heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain
AT soichirokakuta heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain
AT yasuouchiyama heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain
AT kiyohitomizutani heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain
AT yoshimitakai heterogeneityofperivascularastrocyteendfeetdependingonvascularregionsinthemousebrain