miR-124 regulates cerebromicrovascular function in APP/PS1 transgenic mice via C1ql3.

miR-124 regulates cerebromicrovascular function in APP/PS1 transgenic mice via C1ql3.

Publication date: Sep 06, 2019

Many neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease, are associated with microvascular dysfunction, but the cellular and molecular mechanisms are poorly understood. Recently, microRNAs (miRNAs) have been suggested to be involved in the microvascular dysfunction and subsequent memory impairment. MicroRNA-124 (miR-124) is one of the most abundant miRNAs in the brain that is dysregulated in the hippocampus of AD animals. To explore the role of miR-124 in AD pathology, we employed the APP/PS1 transgenic mice and found downregulation of miR-124 and upregulation of complement C1q-like protein 3 (C1ql3) in the hippocampus and cerebral cortex. Downregulation of miR-124 expression resulted in Aβ deposition and a variety of cerebromicrovascular impairments, including the decline in microvascular density, reduced angiogenesis, accompanied by C1ql3 alteration. Treatment with lentivirus-mediated overexpression of miR-124 or the C1q inhibitor C1INH rescued breakdown of blood-brain barrier, promoted angiogenesis and reduced Aβ deposition, and finally alleviated learning and memory deficit in APP/PS1 mice. Moreover, we found that C1ql3, a component of the classical complement, might be a potential target of miR-124. These results suggested that miR-124 was involved in the angiogenesis and vascular integrity in the hippocampus and the cerebral cortex of the AD mice by regulating the classical complement C1ql3.

Li, A.D., Tong, L., Xu, N., Ye, Y., Nie, P.Y., Wang, Z.Y., and Ji, L.L. miR-124 regulates cerebromicrovascular function in APP/PS1 transgenic mice via C1ql3. 22229. 2019 Brain Res Bull.

Concepts Keywords
Alzheimer Disease microvascular dysfunction
Angiogenesis MicroRNA
Blood Brain Barrier Gene expression
Brain Genetics
C1q
Cerebral Cortex
Complement
Downregulation
Hippocampus
Inhibitor
Lentivirus
Memory
Memory Deficit
Mice
MicroRNA
MicroRNAs
Neurodegenerative Diseases
Parkinson
Pathology
Transgenic

Semantics

Type Source Name
disease MESH memory deficit
gene UNIPROT SERPING1
pathway BSID Angiogenesis
pathway BSID Neurodegenerative Diseases
disease MESH neurodegenerative diseases
gene UNIPROT C1QL3
gene UNIPROT PSEN1
gene UNIPROT APP
gene UNIPROT MLXIP
gene UNIPROT MYLIP
gene UNIPROT MARCH8

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