TitleAge-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction
AuthorsPan, Jie
Ma, Nana
Zhong, Jie
Yu, Bo
Wan, Jun
Zhang, Wei
AffiliationGreater Bay Biomed Innoctr, Shenzhen Bay Lab, Shenzhen, Guangdong, Peoples R China
Stanford Univ, Dept Pathol & Neuropathol, Sch Med, Stanford, CA 94305 USA
Shenzhen Peking Univ, Biomed Res Inst, Shenzhen Key Lab Neuronal Struct Biol, Hong Kong Univ Sci & Technol,Med Ctr, Shenzhen, Guangdong, Peoples R China
Shenzhen Peking Univ, Biomed Res Inst, Shenzhen Key Lab Translat Med Dermatol, Hong Kong Univ Sci & Technol,Med Ctr, Shenzhen, Guangdong, Peoples R China
Peking Univ, Dept Dermatol, Shenzhen Hosp, Shenzhen, Guangdong, Peoples R China
Southern Univ Sci & Technol, Sch Life Sci, Dept Biol, Shenzhen, Guangdong, Peoples R China
KeywordsNEUROENDOCRINE PEPTIDE PRECURSOR
ALZHEIMERS-DISEASE
TIGHT JUNCTIONS
C4B-BINDING PROTEIN
CEREBROSPINAL-FLUID
NUCLEAR RECEPTORS
DOWN-REGULATION
TAU INCLUSIONS
KINASE PATHWAY
PROSAAS
Issue Date3-Dec-2021
PublisherMOLECULAR THERAPY-NUCLEIC ACIDS
AbstractBlood-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.
URIhttp://hdl.handle.net/20.500.11897/632695
ISSN2162-2531
DOI10.1016/j.omtn.2021.08.030
IndexedSCI(E)
Appears in Collections:化学生物学与生物技术学院
深圳医院

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