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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

Authors 

Youngjeon LeeYoung-Hyun KimS J ParkJae Won HuhSang-Hyun KimSun-Uk KimJi-Su KimKang Jin JeongK M LeeY HongSang Rae LeeKyu Tae Chang

Publisher 

IOS Press

Issue Date 

2014

Citation 

Journal of Alzheimers Disease, vol. 38, no. 2, pp. 251-267

Keywords 

Alzheimer's diseasebraininsulinmonkeyreal-time quantitative polymerase chain reactionstreptozotocin

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.

ISSN 

1387-2877

Link 

http://dx.doi.org/10.3233/JAD-130776

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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