Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction

Pan，Jie1,2; Ma，Nana1; Zhong，Jie3; Yu，Bo4,5; Wan，Jun1,6; Zhang，Wei1

2021-12-03

10.1016/j.omtn.2021.08.030

Molecular Therapy-Nucleic Acids   影响因子和分区

2162-2531

2162-2531

Blood-brain barrier (BBB) dysfunction is associated with an accumulation of neurotoxic molecules and increased infiltration of peripheral cells within the brain parenchyma. Accruing evidence suggests that microglia and astrocytes play a crucial role in the recovery of BBB integrity and the corralling of infiltrating cells into clusters after brain damage, but the mechanisms involved remain unclear. Intriguingly, the results of flow cytometry and immunofluorescence analyses have shown that BBB permeability to peripheral cells is substantially enhanced during normal aging at 12 months in mice. Thus, we used the SMART-seq2 method to perform RNA sequencing of microglia and astrocytes at five time points before and immediately after the BBB permeability change. Our comprehensive analyses revealed that microglia are characterized by marked alterations in the negative regulation of protein phosphorylation and phagocytic vesicles, whereas astrocytes show elevated enzyme or peptidase-inhibitor activity in the recovery of BBB function. Moreover, we identified a cassette of key genes that might ameliorate the insults of pathophysiological events in aging and neurodegenerative disease.

astrocyte blood-brain barrier dysfunction microglia RNA-seq

SCI

英语

通讯

National Natural Scientific Foundation of China[82071586] ; National Key R&D Program of China[2019YFA0508402]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000730245500004

CELL PRESS

2-s2.0-85117887542

Scopus

1.Greater Bay Biomedical Innocenter,Shenzhen Bay Laboratory,Shenzhen,China
2.Department of Pathology and Neuropathology,Stanford University School of Medicine,94305,United States
3.Shenzhen Key Laboratory for Neuronal Structural Biology,Biomedical Research Institute,Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center,Shenzhen,China
4.Shenzhen Key Laboratory for Translational Medicine of Dermatology,Biomedical Research Institute,Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center,Shenzhen,China
5.Department of Dermatology,Peking University Shenzhen Hospital,Shenzhen,China
6.Department of Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen,China

Pan，Jie,Ma，Nana,Zhong，Jie,et al. Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction[J]. Molecular Therapy-Nucleic Acids,2021,26:970-986.

Pan，Jie,Ma，Nana,Zhong，Jie,Yu，Bo,Wan，Jun,&Zhang，Wei.(2021).Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction.Molecular Therapy-Nucleic Acids,26,970-986.

Pan，Jie,et al."Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction".Molecular Therapy-Nucleic Acids 26(2021):970-986.