Citation: HE Zhi-Jun, BAI Yang, ZHAO Qiong-Hui, OUYANG Pei, NI Jia-Zuan, LIU Qiong, GAN Wen-Biao, ZHANG Xue-Ji. Application of in Vivo Fluorescence Imaging and Metal Ion Detection for Investigation of Bis (ethylmaltolato) Oxidovanadium(Ⅳ) on Alzheimer's Disease[J]. Chinese Journal of Analytical Chemistry, ;2019, 47(10): 1680-1688. doi: 10.19756/j.issn.0253-3820.191426 shu

Application of in Vivo Fluorescence Imaging and Metal Ion Detection for Investigation of Bis (ethylmaltolato) Oxidovanadium(Ⅳ) on Alzheimer's Disease

1.
College of Life Sciences & Oceanography, Shenzhen University, Shenzhen 518055, China;
2.
Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China;
3.
College of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518055, China;
4.
Shenzhen Food Inspection Center of CIQ, Shenzhen 518042, China

Received Date: 20 July 2019
Revised Date: 28 August 2019

Fund Project: This work was supported by the National Natural Science Foundation of China (Nos. 21877081, 21890740, 21890742, 21727815), the Guangdong Natural Science Foundation for Major Cultivation Project (No. 2018B030336001) and the Shenzhen Science and Technology Foundation (No. JCYJ20180305124018343).

Alzheimer's disease (AD) is a major type of dementia in the elderly. Clinical medication at present can only relieve symptoms but has no therapeutical effect. Thus, it is urgent to develop an effective drug for the treatment of AD. In this study, 2-month-old triple transgenic AD model mice (3×Tg-AD) were treated respectively with 0.2 and 1.0 mmol/L bis(ethylmaltolato) oxidovanadium IV (BEOV) in drinking water for 2 months. The open field test, the elevated plus-maze test and the Y maze test were applied to those mice, showing that BEOV could significantly improve the exploratory ability, memory capacity and exercise ability and relieve the anxiety of 4-month-old 3×Tg-AD mice. The dendritic spines of pyramidal neurons in neocortex were detected by in-vivo two-photon imaging of YFP and AD-YFP mice (the offspring of 3×Tg-AD and YFP mice). The numbers of dendritic spines increased in YFP mice but decreased in AD-YFP mice from 2.5-month-old to 3.5-month-old. Treatment with 1.0 mmol/L BEOV in the AD-YFP mice significantly increased the numbers of total dendritic spines, mushroom spines and thin spines, which suggested that BEOV could protect cortical neurons and reduce the loss of dendritic spines. The levels of metal ions in the brain of mice were further measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that 1.0 mmol/L BEOV could significantly increase the levels of V and Se and decrease the levels of Fe, Zn, Hg, Pb, Bi and Ni in AD brains, implying that vanadium might synergize with selenium to regulate the levels of metal ions in AD mice. Summarily, BEOV could mediate the homeostasis of multiple metal ions in AD brain and protect cortical neurons and thus to interfere with the pathological process of AD.
- Alzheimer's disease,
- Bis(ethylmaltolato) oxidovanadium IV,
- In-vivo fluorescence imaging,
- Dendritic spines,
- Inductively coupled plasma mass spectrometry
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