脳ペリサイトの老化関連随伴分泌現象（SASP）により誘発される血液脳関門機能障害

• Published in: 日本薬理学会年会要旨集 p. 3-P-261
• Main Authors: 岩尾, 卓朗, 高田, 芙友子, 松本, 純一, 道具, 伸也, 後藤, 佑希
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: blood-brain barrier; vascular endothelial cell; vascular permeability; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-P-261

Aging is associated with dysfunction of blood-brain barrier (BBB), which is formed by brain vascular endothelial cells, astrocytes and brain pericytes. Senescence associated secretory phenotype (SASP) contributes to pathogenesis of age-related neurodegenerative disease. However, it is unclear how SASP affect BBB functions. Here, we investigated cellular senescence in pericytes, especially its impact on BBB function using low passage (P2) and high passage (P7) rat brain pericytes. Barrier function of the BBB is assessed by transendothelial electronic resistance (TEER) and permeability of sodium fluorescein (Na-F) using rat brain endothelial cells (RBECs) cocultured with P2 or P7 pericytes.In P7 pericytes compared with P2 pericytes, expression levels of β-Galactosidase, Cdkn2a and Cdkn1a mRNA, which are characteristic markers of senescent cells, were significantly increased. Significant increases in p-NF-κB, IL-6, MMP-9 and IL-1β proteins are observed in P7 pericytes. In particular, IL-6 release was markedly increased. Both P2 and P7 pericytes elevated TEER of RBECs, while P7 pericytes failed to increase TEER to the extent of P2 pericytes. Unlike P2 pericytes, P7 pericytes did not decrease the permeability of RBECs to Na-F. Our findings suggest that senescent brain pericytes exhibited SASP through activation NF-κB signaling pathway. Therefore, senescent brain pericytes could induce BBB dysfunction by their SASP.