Characterization of cerebral damage in a monkey model of Alzheimer’s disease induced by intracerebroventricular injection of streptozotocin = 뇌실내 streptozotocin을 주입한 원숭이 알츠하이머병 유발 모델에서 뇌손상의 특성 규명

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Title
Characterization of cerebral damage in a monkey model of Alzheimer’s disease induced by intracerebroventricular injection of streptozotocin = 뇌실내 streptozotocin을 주입한 원숭이 알츠하이머병 유발 모델에서 뇌손상의 특성 규명
Author(s)
Hyeon Gu Yeo; Youngjeon Lee; Chang Yeop Jeon; Kang Jin Jeong; Yeung Bae Jin; Philyong KangSun-Uk KimJi-Su KimJae Won HuhYoung-Hyun KimBo Woong SimBong-Seok SongYoung Ho Park; Y Hong; Sang-Rae Lee; Kyu Tae Chang
Bibliographic Citation
Journal of Alzheimers Disease, vol. 46, no. 4, pp. 989-1005
Publication Year
2015
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.
Keyword
Alzheimer's diseaseanimal modelbrainmonkeystreptozotocin
ISSN
1387-2877
Publisher
IOS Press
DOI
http://dx.doi.org/10.3233/JAD-143222
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
Jeonbuk Branch Institute > Primate Resources Center > 1. Journal Articles
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