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bioRxiv · 10.1101/2023.09.10.557061

Reduced SV2A and GABAA receptor levels in the brains of type 2 diabetic rats revealed by flumazenil PET

Kong, Y.·Xie, F.·Wang, X.·Zuo, C.·Shi, K.·Rominger, A.·Huang, Q.·Xiao, J.·Jiang, D.·Guan, Y.·Ni, R.
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Abstract

PurposeType 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimers 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), {gamma};-aminobutyric acid type A (GABAA) receptor, amyloid-{beta}, 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 (GABAA receptor), [18F]florbetapir (amyloid-{beta}), [18F]PM-PBB3 (tau), and [18F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and Sprague{square}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 GABAA receptor levels in the brains of aged T2DM ZDF rats.

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Kong, Y., Xie, F., Wang, X., Zuo, C., Shi, K., Rominger, A., Huang, Q., Xiao, J., Jiang, D., Guan, Y., Ni, R.. 2023-09-13. Reduced SV2A and GABAA receptor levels in the brains of type 2 diabetic rats revealed by flumazenil PET. https://doi.org/10.1101/2023.09.10.557061

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