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

Abstract

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) was treated with 0.2 and 1.0 mM bis(ethylmaltolato) oxidovanadium IV (BEOV) in drinking water for 2 months respectively. The results of open field test, elevated plus-maze test and Y maze test showed 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 neuron 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 BEOV (1.0 mM) 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 contents of metal ions in the brain of mice were further measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that BEOV (1.0 mM) could significantly increase the contents of V and Se and decrease the contents of Fe, Zn, Hg, Pb, Bi and Ni in AD brains, implying that vanadium might synergize with selenium to regulate the contents of metal ions in AD mice. Summarily, BEOV could mediate the homeostasis of multiple metal ions in AD brain and protect cortical neurons by reducing the loss of dendritic spines, thus to interfere with the pathological process of AD. BEOV could alleviate the anxiety of AD mice and improve their exploratory ability and memory capacity. Pathogenic study revealed that BEOV could regulate the homeostasis of multiple metal ions and inhibit the loss of dendritic spines in the brain of AD mice, thus interfering with the pathological process of AD.