Kong, Yanyan; Cao, Lei; Xie, Fang; Wang, Xiuzhe; Zuo, Chuantao; Shi, Kuangyu; Rominger, Axel; Huang, Qi; Xiao, Jianfei; Jiang, Donglang; Guan, Yihui; Ni, Ruiqing (2024). Reduced SV2A and GABAA receptor levels in the brains of type 2 diabetic rats revealed by [18F]SDM-8 and [18F]flumazenil PET. Biomedicine & pharmacotherapy, 172(116252), p. 116252. Elsevier 10.1016/j.biopha.2024.116252
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PURPOSE
Type 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 2 A (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.
METHODS
Positron emission tomography (PET) using [18F]SDM-8 (SV2A), [18F]flumazenil (GABAA receptor), [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 SpragueDawley (SD) rats. Immunofluorescence staining, Thioflavin S staining, proteomic profiling and pathway analysis were performed on the brain tissues of ZDF and SD rats.
RESULTS
Reduced cortical [18F]SDM-8 uptake and cortical and hippocampal [18F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. The regional uptake of [18F]florbetapir and [18F]PM-PBB3 was comparable in the brains of 12-month-old ZDF and SD rats. Immunofluorescence staining revealed Thioflavin S-negative, phospho-tau-positive inclusions in the cortex and hypothalamus in the brains of ZDF rats and the absence of amyloid-beta deposits. The level of GABAA receptors was lower in the cortex of ZDF rats than SD rats. Proteomic analysis further demonstrated that, compared with SD rats, synaptic-related proteins and pathways were downregulated in the hippocampus of ZDF rats.
CONCLUSION
These findings provide in vivo evidence for regional reductions in SV2A and GABAA receptor levels in the brains of aged T2DM ZDF rats.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine |
UniBE Contributor: |
Shi, Kuangyu, Rominger, Axel Oliver |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1950-6007 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
12 Feb 2024 14:15 |
Last Modified: |
03 Mar 2024 00:18 |
Publisher DOI: |
10.1016/j.biopha.2024.116252 |
PubMed ID: |
38325265 |
Uncontrolled Keywords: |
Amyloid-beta GABA(A) receptor SV2A Tau Type 2 diabetes mellitus |
BORIS DOI: |
10.48350/192683 |
URI: |
https://boris.unibe.ch/id/eprint/192683 |
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