Disruption of normal brain distribution of [18F]Nifene to α4β2*nicotinic acetylcholinergic receptors in old B6129SF2/J mice and transgenic 3xTg-AD mice model of Alzheimer's disease: In Vivo PET/CT imaging studies

被引:1
作者
Liang, Christopher [1 ]
Okamoto, Atsumi A. [1 ]
Karim, Fariha [1 ]
Kawauchi, Shimako [2 ]
Melkonyan, Lusine [1 ]
Danh, Tram B. [1 ]
Mukherjee, Jogeshwar [1 ]
机构
[1] Univ Calif Irvine, Dept Radiol Sci, Preclin Imaging, Med Sci B140, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Univ Lab Anim Resources, Res Off, Transgen Mouse Facil, Irvine, CA USA
关键词
18F]Nifene; PET/CT; 3xTg-AD mice; B2169SF2/J mice; 125I]IBETA; Alzheimer's disease; CORTEX;
D O I
10.1016/j.neuroimage.2025.121092
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The 3xTg-AD transgenic mouse model develops A beta plaque and tau pathology and is purported to closely resemble pathological development in the human Alzheimer's disease (AD) brain. Nicotinic acetylcholine receptors (nAChRs) alpha 4 beta 2* subtype, was studied in this mouse model using [18F]nifene PET/CT and compared with nontransgenic B6129SF2/J mice (male and female). Young 2-month old B6129SF2/J exhibited normal [18F] nifene distribution (measured as standard uptake volume ratios, SUVR with cerebellum as reference) thalamus (TH) 3.12> medial prefrontal cortex (mPFC) 2.33> frontal cortex (FC) 2.06> hippocampus-subiculum (HP-SUB) 1.6. At 11-months of age, B6129SF2/J exhibited high, irreversible and non-saturable [18F]nifene binding in mPFC higher than in TH (mPFC 3.8> TH 2.82> FC 1.79> HP-SUB 1.73). The 3xTg-AD also exhibited high mPFC binding, although the region of highest binding within the mPFC was different compared to B6129SF2/J mice (mPFC 2.44> TH 2.27> FC 1.61> HP-SUB 1.48). [125I]IBETA and immunohistochemistry in 3xTg-AD brain slices confirmed A beta plaques. The TH of 3xTg-AD mice had lower [18F]nifene binding (reduced by approximately 20%) compared to both, young and old B6129SF2/J, and was significant. The mPFC [18F]nifene binding was significantly higher in the old B6129SF2/J compared to both the young B6129SF2/J and the 3xTg-AD mice (>150 %). Overall, 3xTg-AD transgenic mice had reduced [18F]nifene binding compared to B6129SF2/J controls, suggesting possible effects of A beta plaques and Tau on alpha 4 beta 2* nAChRs.
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页数:15
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