Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression

Liu, Huan; Tian, Tian; Qin, Shanchun; Li, Wen; Zhang, Xumei; Wang, Xuan; Gao, Yuxia; Huang, Guowei

doi:10.1016/j.jnutbio.2015.07.020

Cited by 35 publications

(24 citation statements)

References 31 publications

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“…We have demonstrated folic acid deficiency increased Aβ42 but not Aβ40 in APP/PS1 mice brain [ 19 ]. Moreover, the present study revealed that folic acid supplementation still decreased Aβ42 compared to Aβ40.…”

Section: Discussionmentioning

confidence: 99%

“…However, miR-339-5p expression showed a reverse trend compared to miR-126-3p. In a previous study we have revealed folic acid deficiency down-regulated miR-339-5p, which targets BACE1 [ 19 ]. In the current study, we demonstrated folic acid supplementation could up-regulate miR-339-5p and down-regulate BACE1 expression, which can further confirm the relationship between folic acid, miR-339-5p and BACE1.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, we have found folate deficiency elevated hippocampal APP, PS1 and total Aβ protein levels in APP/PS1 mice, and these rises were prevented by folic acid [ 18 ]. Furthermore, we have discovered folic acid deficiency can decrease several amyloid-associated miRNAs expression which may target APP and BACE1 [ 19 ]. PS1 and BACE1 are both important secretases involved in Aβ production, so we hypothesized that folic acid may influence the expression of multiple secretases related to APP processing and Aβ accumulation.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

Tian

Dong

et al. 2016

Nutrients

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Alzheimer’s disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component—presenilin 1 (PS1)—in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

Tian

Dong

et al. 2016

Nutrients

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“…The APP/PS1 mouse strain ( 10 ) is a double-transgenic hemizygote that expresses a chimeric mouse/human amyloid precursor protein and mutant human presenilin-1. The transgenic mice were used as they develop behavioral and pathology features of AD similar to patients and the mice have been widely used in AD studies worldwide ( 11 ). C57BL/6 mice were used as age-matched controls and APP/PS1 transgenic mice were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China), while C57BL/6 mice were obtained from the Experimental Animal Center of Shanghai Academy (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Effect of the herbal formulation Shen-Zhi-Ling on an APP/PS1 mouse model of Alzheimer's disease by modulating the biliverdin reductase/heme oxygenase 1 system

Shen

Chen

et al. 2017

Experimental and Therapeutic Medicine

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Shen-Zhi-Ling (SZL) oral liquid is a traditional Chinese medicine formula that is mainly used for the clinical treatment of mild to moderate Alzheimer's disease (AD). The aim of the present study was to investigate the effects and underlying mechanisms of SZL treatment on AD. APP/PS1 transgenic mice were utilized to evaluate the effect of SZL treatment (0.5 g/20 g/day). Morris water maze and Thioflavin S staining analyses were used to evaluate the cognitive impairment and β-amyloid plaques, respectively, while quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression levels of heme oxygenase 1 (HO-1) and biliverdin reductase (BVR). Furthermore, immunofluorescence staining was used to measure the BVR and HO-1 protein levels in the hippocampus. The findings of the current study demonstrated that SZL treatment was able to ameliorate the impairment of memory and reduce the accumulation of amyloid plaques, and its ameliorating effects may be attributed to the modulation of the HO-1/BVR system in the hippocampus. These results indicate that SZL may be a possible complementary and alternative therapy to delay the development of AD.

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“…The vitamin exists extensively in fresh fruits, leafy vegetables, and meat products. A deficiency in FA leads to nerve system damage, irritability, megaloblastic anemia, diarrhea, and psychiatric disorders (Chang et al, 2015;Liu et al, 2015;Srivastav, Singh, Yadav, & Srikrishna, 2015;Vasquez & Suarez-Obando, 2015). In pregnant women, FA deficiency results in neural tube defects, developmental retardation, and early spontaneous abortion (Barco Tavares, Neves Finochio Sabino, Lima, & Tozzo Garcia, 2015;Leuckx, 2015;Smithells, Sheppard, & Schorah, 1976).…”

Section: Introductionmentioning

confidence: 99%

Development of ic-ELISA and lateral-flow immunochromatographic assay strip for the detection of folic acid in energy drinks and milk samples

Kong

Liu

Song

et al. 2016

Food and Agricultural Immunology

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Folic acid (FA) is an important vitamin for human growth and development, especially for pregnant women. A sensitive, rapid, and accurate FA detection method is required to assess the nutritional quality and safety of foods. A monoclonal antibody against FA was prepared for the development of indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and lateral-flow immunochromatographic assay (ICA) strip. The 50% inhibitory concentration and limit of detection of ic-ELISA were 0.12 and 0.018 ng/ml, respectively. The visual limit of detection and cut-off values of the lateral-flow ICA strip were 0.5 and 2.5 ng/ ml, respectively. Using the ICA strip, FA recovery rates were 89-98% from energy drinks and 73-87% for milk samples and were in good agreement with those obtained from the conventional microbiological assay method. Our developed methods are sensitive, convenient, effective, and suitable for on-site detection and rapid mass screening of food samples. ARTICLE HISTORY

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Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression

Cited by 35 publications

References 31 publications

Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

Effect of the herbal formulation Shen-Zhi-Ling on an APP/PS1 mouse model of Alzheimer's disease by modulating the biliverdin reductase/heme oxygenase 1 system

Development of ic-ELISA and lateral-flow immunochromatographic assay strip for the detection of folic acid in energy drinks and milk samples

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