title: Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys.
abstract: Intracerebroventricular injection of streptozotocin (icv-STZ) in rodents induces cellular and behavioral features mimicking Alzheimer's disease (AD). However, the effect of icv-STZ in terms of regional cerebral glucose metabolism has not yet been examined in vivo. Given that regionally specific hypometabolism of glucose is a consistent neuroimaging marker in early AD, we monitored 18F-deoxyglucose uptake using a high-resolution micro-PET after icv-STZ in non-human primates. Two cynomolgus monkeys (Macaca fascicularis) received STZ (2 mg/kg), and another two were given normal saline as controls, at the cerebellomedullary cistern (CM) three times (day 1, 7, and 14). FDG-PET, as well as MRI for structural evaluation, was performed immediately before, six weeks after, and 12 weeks after the first icv injection. In the STZ group, FDG uptake decreased significantly in comparison to the pre-injection baseline, at the precuneus, the posterior cingulate, and medial temporal cortices. Increase in sulcal markings suggesting brain atrophy was observed by MRI at six weeks post-injection. The structural changes normalized at 12 weeks, but the reduced FDG uptake persisted at the same loci. The cortical distribution of glucose hypometabolism was similar to that at early stages of AD patients. The findings demonstrate that the effect of icv-STZ is regionally specific, lending further support for the method as a model of AD pathogenesis.
authors.affiliation: Department of Neurology, Seoul Medical Center, Seoul, Korea.
authors.forename: Jae-Hyeok
authors.initials: JH
authors.lastname: Heo
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Kyoung-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Dong-Pyo
authors.initials: DP
authors.lastname: Jang
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
authors.forename: Zang-Hee
authors.initials: ZH
authors.lastname: Cho
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D001931:Brain Mapping; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D044882:Glucose Metabolism Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*; D007276:Injections, Intraventricular; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography / Q000379:methods; D013311:Streptozocin / Q000633:toxicity*; D013997:Time Factors
chemical_list: D019788:Fluorodeoxyglucose F18; D013311:Streptozocin