title: Behavioral stress reduces RIP140 expression in astrocyte and increases brain lipid accumulation.
abstract: Receptor-interacting protein 140 (RIP140) is highly expressed in the brain, and acts in neurons and microglia to affect emotional responses. The present study reveals an additional function of RIP140 in the brain, which is to regulate brain lipid homeostasis via its action in astrocytes. We found forced swim stress (FSS) significantly reduces the expression level of RIP140 and elevates cholesterol content in the brain. Mechanistically, FSS elevates endoplasmic reticulum stress, which suppresses RIP140 expression by increasing microRNA 33 (miR33) that targets RIP140 mRNA's 3'-untranslated region. Consequentially, cholesterol biosynthesis and export are dramatically increased in astrocyte, the major source of brain cholesterol. These results demonstrate that RIP140 plays an important role in maintaining brain cholesterol homeostasis through, partially, regulating cholesterol metabolism in, and mobilization from, astrocyte. Altering RIP140 levels can disrupt brain cholesterol homeostasis, which may contribute to behavioral stress-induced neurological disorders.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, United States.
authors.forename: Xudong
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, United States.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, United States. Electronic address: weixx009@umn.edu.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wei
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D013550:Swimming
chemical_list: D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse; D056971:Nuclear Receptor Co-Repressor 1; D002784:Cholesterol
keywords: Astrocyte; Cholesterol; RIP140; Stress