Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin

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Title
Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin
Author(s)
Youngjeon LeeYoung-Hyun KimSang Je ParkJae Won Huh; Sang-Hyun Kim; Sun-Uk KimJi-Su KimKang Jin Jeong; K M Lee; Y Hong; Sang Rae Lee; Kyu Tae Chang
Bibliographic Citation
Journal of Alzheimers Disease, vol. 38, no. 2, pp. 251-267
Publication Year
2014
Abstract
We reported previously that the intracerebroventricular streptozotocin (icv-STZ)-treated cynomolgus monkey showed regionally specific glucose hypometabolism in FDG-PET imaging, similar to that observed in the early stages of sporadic Alzheimer's disease (sAD). However, further pathological analyses of this model at the molecular level are needed to validate it as a feasible model for sAD. Two cynomolgus monkeys were injected with 2 mg/kg STZ into the cerebellomedullary cistern at day 1, 7 and 14. Two control monkeys were given normal saline. At 5 months after injection, the expression levels of genes encoding 9 upstream molecules in insulin/insulin-like growth factor (IGF) signaling and markers for 4 cell-type populations in the frontal cortex, hippocampus, posterior cingulate, precuneus, and occipital cortex of control and icv-STZ treated cynomolgus monkeys were examined. Real-time quantitative PCR analyses demonstrated that the overall mRNA expression of insulin/IGF signaling-related genes was mainly impaired in the anterior part of the cerebrum, frontal cortex, and hippocampus, similar to the early stage of sAD. The changes were accompanied by the loss of oligodendrocytes and neurons. The posterior part of the cerebrum did not show degenerative alterations. The present study provides important fundamental information on the icv-STZ monkey model for sAD. These results may help guide future studies using this model for the investigation of pathological mechanisms and the development of drugs for sAD.
Keyword
Alzheimer's diseasebraininsulinmonkeyreal-time quantitative polymerase chain reactionstreptozotocin
ISSN
1387-2877
Publisher
IOS Press
DOI
http://dx.doi.org/10.3233/JAD-130776
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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