title: Characterization of Cerebral Damage in a Monkey Model of Alzheimer's Disease Induced by Intracerebroventricular Injection of Streptozotocin.
abstract: In line with recent findings showing Alzheimer's disease (AD) as an insulin-resistant brain state, a non-transgenic animal model with intracerebroventricular streptozotocin (icv-STZ) administration has been proposed as a representative experimental model of AD. Although icv-STZ rodent models of AD have been increasingly researched, studies in non-human primate models are very limited. In this study, we aimed to characterize the cerebral damage caused by icv-STZ in non-human primates; to achieve this, three cynomolgus monkeys (Macaca fascicularis) were administered four dosages of STZ (2 mg/kg) dissolved in artificial cerebrospinal fluid and another three controls were injected with only artificial cerebrospinal fluid at the cerebellomedullary cistern. In vivo neuroimaging was performed with clinical 3.0 T MRI, followed by quantitative analysis with FSL for evaluation of structural changes of the brain. Immunohistochemistry was performed to evaluate cerebral histopathology. We showed that icv-STZ caused severe ventricular enlargement and parenchymal atrophy, accompanying amyloid-β deposition, hippocampal cell loss, tauopathy, ependymal cell loss, astrogliosis, and microglial activation, which are observed in human aged or AD brain. The findings suggest that the icv-STZ monkey model would be a valuable resource to study the mechanisms and consequences of a variety of cerebral pathologies including major pathological hallmarks of AD. Furthermore, the study of icv-STZ monkeys could contribute to the development of treatments for age- or AD-associated cerebral changes.
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Hyeon-Gu
authors.initials: HG
authors.lastname: Yeo
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Youngjeon
authors.initials: Y
authors.lastname: Lee
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.|Department of Biomedical Engineering, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Chang-Yeop
authors.initials: CY
authors.lastname: Jeon
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Kang-Jin
authors.initials: KJ
authors.lastname: Jeong
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Yeung Bae
authors.initials: YB
authors.lastname: Jin
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Philyong
authors.initials: P
authors.lastname: Kang
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Ji-Su
authors.initials: JS
authors.lastname: Kim
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Huh
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Young-Hyun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Bo-Woong
authors.initials: BW
authors.lastname: Sim
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Song
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.affiliation: Department of Rehabilitation Science, Graduate School of Inje University, Gimhae, Republic of Korea.
authors.forename: Yonggeun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D057967:Infusions, Intraventricular; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D018709:Statistics, Nonparametric; D013311:Streptozocin / Q000633:toxicity*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D000903:Antibiotics, Antineoplastic; D005904:Glial Fibrillary Acidic Protein; D013311:Streptozocin
keywords: Alzheimer’s disease; animal model; brain; monkey; streptozotocin