Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain
Takeshi Kameyama,
Muneaki Miyata,
Hajime Shiotani,
Jun Adachi,
Soichiro Kakuta,
Yasuo Uchiyama,
Kiyohito Mizutani,
Yoshimi Takai
Affiliations
Takeshi Kameyama
Division 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, Japan
Muneaki Miyata
Division 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
Hajime Shiotani
Division 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
Jun Adachi
Laboratory 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, Japan
Soichiro Kakuta
Laboratory 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, Japan
Yasuo Uchiyama
Department of Cellular Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Kiyohito Mizutani
Division 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 author
Yoshimi Takai
Division of Pathogenetic Signaling, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; Corresponding author
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.
