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P1‐123: Streptozotocin‐induced Alzheimer model in cynomolgus monkeys
Author(s) -
Heo Jae-Hyeok,
Lee Kyoung-Min,
Lee Sang-Rae,
Lee Soon-Tae,
Oh Jin-Hwan,
Kim Nam-Beom,
Chang Kyu-Tae,
Cho Zang-Hee
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.672
Subject(s) - streptozotocin , medicine , endocrinology , primate , white matter , atrophy , hippocampal formation , cerebrospinal fluid , pathological , diabetes mellitus , magnetic resonance imaging , psychology , neuroscience , radiology
Background: Intracerebroventricular injection of streptozotocin (ICV-STZ) in rats leads to behavioral and pathological changes mimicking Alzheimer’s disease (AD). In this study, we aimed at developing a primate model of AD using similar technique, and monitored metabolic and structural effects of ICV-STZ in cynomolgus monkeys with serial brain 3T MRI and [18F]FDG micro PET/CT images. Methods: Seven cynomolgus monkeys aged 3 years were randomly assigned to one of the following groups: low dose streptozotocin (2mg/kg, n 1⁄4 2), high dose streptozotocin (5mg/kg, n 1⁄4 3), or control (N/S 5mg/kg, n 1⁄4 2). STZ was injected into cerebrospinal fluid (CSF) via the cerebellomedullary cistern (CM) on day 1, 7, and 14. Brain MRIs and micro PET/CT were performed three times: before, 6 weeks after, and 12 weeks after ICV-STZ. Results: In both STZ groups, significant increase in ventricular size and sulcal markings were observed in MRI, consistent with diffuse brain atrophy. Glucose metabolism was also decreased in the cerebral cortex at 6 and 12 weeks after ICV-STZ. T2-high signal intensities were prominent at the periventricular white matter and hippocampal complex in STZ-injected animals, which were dose-dependent: significantly worse in the higher-dose group than in the lower-dose group. Clinically, convulsive seizures were observed in two weeks of ICV-STZ in two animals with higher-dose ICV-STZ, while none were in the lower dose group. No obvious systemic effects were observed in the latter, and post-mortem analysis of one animal in the higher-dose group showed no evidence of systemic derangements due to ICV-STZ, in particular, in pancreatic beta cells. Histological analyses of the brain are currently under way on the injected animals. Conclusions: Injection of STZ into the CSF space in cynomolgus leads to gross morphological and metabolic changes in the brain consistent with AD. Further pathological and behavioral studies are warranted to validate this method for developing a primate AD model.