2023年新着論文 52　病態シグナル学分野から論文が発表されました

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

iScience. 2023 Sep 21;26(10):108010. doi: 10.1016/j.isci.2023.108010. eCollection 2023 Oct 20.

Authors

Takeshi Kameyama^1 2, Muneaki Miyata^1 3, Hajime Shiotani^1 3, Jun Adachi^4 5, Soichiro Kakuta^6 7, Yasuo Uchiyama⁷, Kiyohito Mizutani^1 3, Yoshimi Takai¹

Affiliations

¹ Division of Pathogenetic Signaling, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan.
² Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima 770-8503, Japan.
³ Division of Pathogenetic Signaling, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.
⁴ Laboratory of Proteomics for Drug Discovery, Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
⁵ Laboratory of Clinical and Analytical Chemistry, Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
⁶ Laboratory of Morphology and Image Analysis, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
⁷ Department of Cellular Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.

Abstract

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.

Keywords: Immunology; Molecular neuroscience; Vascular anatomy.

Conflict of interest statement

The authors declare no competing interests.

カテゴリー: ニュース