Synaptic loss and amyloid beta alterations in the rodent hippocampus induced by streptozotocin injection into the cisterna magna

Yujin Ahn1, Ji Hun Seo1, Junghyung Park1, Jinyoung Won1, Hyeon-Gu Yeo1, Keon‐Woo Kim1, Chang‐Yeop Jeon1, Jae‐Won Huh1, Sang-Rae Lee2, Dong‐Seok Lee3, Youngjeon Lee1
1National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea
2Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon, 34113, Republic of Korea
3School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea

Tóm tắt

AbstractTo date, researchers have developed various animal models of Alzheimer’s disease (AD) to investigate its mechanisms and to identify potential therapeutic treatments. A widely recognized model that mimics the pathology of human sporadic AD involves intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injections are an invasive approach, which creates limitations in generalizing the results. In this study, we produced a rodent model of AD using STZ (3 mg/kg) injection via the cisterna magna (CM) once every week for 4 weeks, and analyzed at 4 weeks and 16 weeks after final injection. In the CM-STZ rodent model of AD, we observed increase in extracellular amyloid-beta (Aβ) deposition and decrease and abnormal morphology of post-synaptic protein, PSD95 in 16 weeks STZ-injected group. The model developed using our less-invasive method induced features of AD-like pathology, including significantly increased extracellular amyloid-beta deposition, and decreased synaptic protein in the hippocampus. These findings supporting the success of this alternative approach, and thus, we suggest this is a promising, less invasive model for use in future AD research.

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