title: miR-29a differentially regulates cell survival in astrocytes from cornu ammonis 1 and dentate gyrus by targeting VDAC1.
abstract: Neurons in the cornu ammonis 1 (CA1) region of the hippocampus are vulnerable to cerebral ischemia, while dentate gyrus (DG) neurons are more resistant. This effect is mediated by local astrocytes, and may reflect differences in subregional hippocampal expression of miR-29a. We investigated the role of miR-29a on survival of hippocampal astrocytes cultured selectively from CA1 and DG in response to glucose deprivation (GD). CA1 astrocytes exhibited more cell death and a greater decrease in miR-29a than DG astrocytes. A reciprocal change was observed in the mitochondrial voltage dependent cation channel-1 (VDAC1), a regulator of mitochondria and target of miR-29a. In CA1 astrocytes, increasing miR-29a decreased VDAC1 and improved cell survival, while knockdown of VDAC1 improved survival. Finally, the protective effect of miR-29a was eliminated by inhibition of miR-29a/VDAC1 binding. These findings suggest that the selective vulnerability of the CA1 to injury may be due in part to a limited miR-29a response in CA1 astrocytes, allowing a greater increase in VDAC1-mediated cellular dysfunction in CA1 astrocytes.
authors.affiliation: Dept. of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305-5117, USA. Electronic address: cstary@stanford.edu.
authors.forename: Creed M
authors.initials: CM
authors.lastname: Stary
authors.affiliation: Dept. of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305-5117, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Dept. of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305-5117, USA.
authors.forename: YiBing
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Dept. of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305-5117, USA; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou 510280, Guangdong Province, China.
authors.forename: Le
authors.initials: L
authors.lastname: Li
authors.affiliation: Dept. of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305-5117, USA.
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
chemical_list: C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C494763:Vdac1 protein, mouse; D050995:Voltage-Dependent Anion Channel 1
keywords: Brain; Glia; Glucose deprivation; Hippocampus; Ischemia; MicroRNA; Mitochondria; Stroke