Spatial Distribution of Glucose Hypometabolism Induced by Intracerebroventricular Streptozotocin in Monkeys

Article type: Research Article

Authors: Heo, Jae-Hyeok^{a; 1} | Lee, Sang-Rae^{b; 1} | Lee, Soon-Tae^c | Lee, Kyoung-Min^c | Oh, Jin-Hwan^d | Jang, Dong-Pyo^d | Chang, Kyu-Tae^{b; *} | Cho, Zang-Hee^d

Affiliations: [a] Department of Neurology, Seoul Medical Center, Seoul, Korea | [b] National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Korea | [c] Department of Neurology, Seoul National University Hospital, Seoul, Korea | [d] Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea

Correspondence: [*] Correspondence to: Kyoung-Min Lee, M.D., Ph.D., Department of Neurology, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea. Tel.: +82 2 2072 2985; Fax: +82 2 3672 7553; E-mail: kminlee@snu.ac.kr. Kyu-Tae Chang, Ph.D., National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, 685-1 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Korea. Tel.: +82 43 240 6300; Fax: +82 43 240 6309; E-mail: changkt@kribb.re.kr.

Note: [1] The first two authors (Heo JH, Lee SR) contributed equally to this work.

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.

Keywords: Alzheimer's disease, cynomolgus, streptozotocin-induced AD model

DOI: 10.3233/JAD-2011-102079

Journal: Journal of Alzheimer's Disease, vol. 25, no. 3, pp. 517-523, 2011