Exposure to fluoride aggravates the impairment in learning and memory and neuropathological lesions in mice carrying the APP/PS1 double-transgenic mutation

Abstract

Background: Alzheimer's disease (AD) is responsible for 60-70% of all cases of dementia. On the other hand, the tap water consumed by hundreds of millions of people has been fluoridated to prevent tooth decay. However, little is known about the influence of fluoride on the expression of APP and subsequent changes in learning and memory and neuropathological injury. Our aim here was to determine whether exposure to fluoride aggravates the neuropathological lesions in mice carrying the amyloid precursor protein (APP)/presenilin1 (PS1) double mutation. Methods: These transgenic or wide-type (WT) mice received 0.3 ml of a solution of fluoride (0.1 or 1 mg/ml, prepared with NaF) by intragastric administration once each day for 12 weeks. The learning and memory of these animals were assessed with the Morris water maze test. Senile plaques, ionized calcium binding adaptor molecule 1 (Iba-1), and complement component 3 (C3) expression were semi-quantified by immunohistochemical staining; the level of Aβ42 was detected by Aβ42 enzyme-linked immunosorbent assays (ELISAs); the levels of synaptic proteins and enzymes that cleave APP determined by Western blotting; and the malondialdehyde (MDA) content and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) measured by biochemical procedures. Results: The untreated APP mice exhibited a decline in learning and memory after 12 weeks of fluoride treatment, whereas treatment of these some animals with low or high levels of fluoride led to such declines after only 4 or 8 weeks, respectively. Exposure of APP mice to fluoride elevated the number of senile plaques and level of Aβ42, Iba-1, and BACE1, while reducing the level of ADAM10 in their brains. The lower levels of synaptic proteins and enhanced oxidative stress detected in the hippocampus of APP mice were aggravated to fluoride. Conclusions: These findings indicate that exposure to fluoride, even at lower concentration, can aggravate the deficit in learning and memory and neuropathological lesions of the mice that express the high level of APP.

Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice

“…In previous studies, it has been demonstrated that APP/PS1 mice showed cognitive decline in terms of spatial learning and memory [ 30 , 38 , 39 ]. Therefore, we evaluated whether DXI was able to rescue the cognitive impairment observed in this mice model through both tests, MWM and NORT.…”

Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice

“…In previous studies, it has been demonstrated that APP/PS1 mice showed cognitive decline in terms of spatial learning and memory (30,38,39). Therefore, we evaluated whether DXI was able to rescue the cognitive impairment observed in this mice model through both tests, MWM and NORT.…”

The Mechanism by Which LiCl Attenuates the Impaired Ability of Learning and Memory of APP/PS1 Double Transgenic Mice May Involve Elevating the Expression of a7 Nicotinic Acetylcholine Receptors via Regulation of the Wnt/β-catenin Pathway

“…Each mouse was forced to find a submerged escape platform in a circular pool filled with water (25-26° C) rendered opaque with powdered milk [50]. During the familiarization session and acquisition phase (four trials/day for four consecutive days), the mouse was given as long as 60 s to find the hidden platform and then allowed to remain seated on this platform for 5 s, after which the animal was returned to its home cage.…”

“…The level of Aβ42 in mouse brains was determined utilizing an Amyloid β42 Mouse ELISA kit in accordance with the manufacturer's protocol [50]. In brief, after homogenization and centrifugation of the tissue, the pellets obtained were extracted with 5 M guanidine-HCl.…”