Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin.
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.
National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea.
Youngjeon
Y
Lee
Young-Hyun
YH
Kim
Sang-Je
SJ
Park
Jae-Won
JW
Huh
Sang-Hyun
SH
Kim
Sun-Uk
SU
Kim
Ji-Su
JS
Kim
Kang-Jin
KJ
Jeong
Kyoung-Min
KM
Lee
Yonggeun
Y
Hong
Sang-Rae
SR
Lee
Kyu-Tae
KT
Chang
D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D008252:Macaca fascicularis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D007328:Insulin; D012333:RNA, Messenger; D013002:Somatomedins; D013311:Streptozocin
Alzheimer's disease; brain; insulin; monkey; real-time quantitative polymerase chain reaction; streptozotocin