Insulin/IGF Signaling-Related Gene Expression in the Brain of a Sporadic Alzheimer's Disease Monkey Model Induced by Intracerebroventricular Injection of Streptozotocin
Affiliations: [a] National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea | [b] Department of Neurology, Seoul National University Hospital, Seoul, Korea | [c] Department of Rehabilitation Science, Graduate School of Inje University, Gimhae, Korea
Correspondence:
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Correspondence to: Kyu-Tae Chang, Ph.D., National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Chungwon-gun, Chungbuk 363-883, Republic of Korea. Tel.: +82 43 240 6300; Fax: +82 43 240 6309; E-mail: [email protected]; or Sang-Rae Lee, D.V.M., Ph.D. Tel.: +82 43 240 6322; Fax: +82 43 240 6309; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
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.
