title: Increased Expression of Osteopontin in the Degenerating Striatum of Rats Treated with Mitochondrial Toxin 3-Nitropropionic Acid: A Light and Electron Microscopy Study.
abstract: The mycotoxin 3-nitropropionic acid (3NP) is an irreversible inhibitor that induces neuronal damage by inhibiting mitochondrial complex II. Neurodegeneration induced by 3NP, which is preferentially induced in the striatum, is caused by an excess influx and accumulation of calcium in mitochondria. Osteopontin (OPN) is a glycosylated phosphoprotein and plays a role in the regulation of calcium precipitation in the injured brain. The present study was designed to examine whether induction of OPN protein is implicated in the pathogenesis of 3NP-induced striatal neurodegeneration. We observed overlapping regional expression of OPN, the neurodegeneration marker Fluoro-Jade B, and the microglial marker ionized calcium-binding adaptor molecule 1 (Iba1) in the 3NP-lesioned striatum. OPN expression was closely associated with the mitochondrial marker NADH dehydrogenase (ubiquinone) flavoprotein 2 in the damaged striatum. In addition, immunoelectron microscopy demonstrated that OPN protein was specifically localized to the inner membrane and matrix of the mitochondria in degenerating striatal neurons, and cell fragments containing OPN-labeled mitochondria were also present within activated brain macrophages. Thus, our study revealed that OPN expression is associated with mitochondrial dysfunction produced by 3NP-induced alteration of mitochondrial calcium homeostasis, suggesting that OPN is involved in the pathogenesis of striatal degeneration by 3NP administration.
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University , Seoul 143-701, Korea ; Integrative Research Support Center, College of Medicine, Catholic University , 137-701, Seoul, Korea.
authors.forename: Hong-Lim
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Catholic University , Seoul 137-701, Korea.
authors.forename: Mun-Yong
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Anatomy, College of Medicine, Catholic University , Seoul 137-701, Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University , Seoul 143-701, Korea.
authors.forename: Doo-Won
authors.initials: DW
authors.lastname: Song
authors.affiliation: Integrative Research Support Center, College of Medicine, Catholic University , 137-701, Seoul, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Cosmetology, Hanseo University , 356-706, Seosan, Chungnam, Korea.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Chang
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University , Seoul 143-701, Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
keywords: 3-nitropropionic acid; microglia; mitochondria; osteopontin