Reduced SV2A and GABAAreceptor levels in the brains of type 2 diabetic rats revealed by [18F]SDM-8 and [18F]flumazenil PET

Author:

Kong Yanyan,Xie FangORCID,Wang Xiuzhe,Zuo ChuantaoORCID,Shi Kuangyu,Rominger AxelORCID,Huang Qi,Xiao Jianfei,Jiang Donglang,Guan Yihui,Ni RuiqingORCID

Abstract

AbstractPurposeType 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimer’s disease. Synaptic impairment and protein aggregates have been reported in the brains of T2DM models. Here, we assessed whether neurodegenerative changes in synaptic vesicle 2A (SV2A), γ;-aminobutyric acid type A (GABAA) receptor, amyloid-β, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats.MethodsPositron emission tomography (PET) using [18F]SDM-8 (SV2A), [18F]flumazenil (GABAAreceptor), [18F]florbetapir (amyloid-β), [18F]PM-PBB3 (tau), and [18F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and Sprague□Dawley (SD) rats. Proteomic profiling and pathway analysis of the hippocampus of ZDF and SD rats were performed.ResultsReduced cortical [18F]SDM-8 and cortical and hippocampal [18F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. [18F]florbetapir and [18F]PM-PBB3 uptake were comparable in the brains of 12-month-old ZDF rats and SD rats.ConclusionThe findings provide in vivo evidence for regional reductions in SV2A and GABAAreceptor levels in the brains of aged T2DM ZDF rats.

Publisher

Cold Spring Harbor Laboratory

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