The preventive effects of edible folic acid on cardiomyocyte apoptosis and survival in early onset triple-transgenic Alzheimer's disease model mice

Kuan Ho Lin; Chih Hao Chiu; Wei Wen Kuo; Da Tong Ju; Chia Yao Shen; Ray Jade Chen; Chien Chung Lin; Vijaya Padma Viswanadha; Jian Sheng Liu; Rwei Fen S. Huang; Chih Yang Huang

doi:10.1002/tox.22498

The preventive effects of edible folic acid on cardiomyocyte apoptosis and survival in early onset triple-transgenic Alzheimer's disease model mice

Kuan Ho Lin, Chih Hao Chiu, Wei Wen Kuo, Da Tong Ju, Chia Yao Shen, Ray Jade Chen, Chien Chung Lin, Vijaya Padma Viswanadha, Jian Sheng Liu, Rwei Fen S. Huang, Chih Yang Huang

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14 Citations (Scopus)

Abstract

In recent years, neuropathological and epidemiological studies have indicated an association between Alzheimer's disease (AD) and several cardiovascular risk factors. In this study, the cardio-protective effects of folic acid (FA) in early stage AD was elucidated using a triple-transgenic (3xTg) Alzheimer's mouse model. Eleven-month-old C57BL/6 mice and 3xTg mice were assigned to five groups. During the four-month treatment period, the low-FA treatment group received FA through their diet, and the high-FA treatment groups received 3 mg/dl folate in drinking water and were also gastric-fed 1.2 mg/kg folate every day. In the C57B1/6J mice, treatment with high doses of FA (HFA) did not show any considerable effect compared to the control group or the low-dose dietary FA treatment group. However, Alzheimer's mice treated with HFA showed enhanced cardio-protection. Western blot analysis revealed that FA treatment restored SIRT1 expression, which was suppressed in 3xTg mice, through enhanced AMPK expression. FA significantly enhanced the IGF1 receptor survival mechanism in the hearts of the 3xTg mice and suppressed the expression-intrinsic and extrinsic apoptosis-associated proteins. The results suggest that FA intake may significantly alleviate cellular pathological events in the heart associated with AD.

Original language	English
Pages (from-to)	83-92
Number of pages	10
Journal	Environmental Toxicology
Volume	33
Issue number	1
DOIs	https://doi.org/10.1002/tox.22498
Publication status	Published - Jan 2018

Keywords

Alzheimer's disease
apoptosis
folic acid
preventive effects
survival

ASJC Scopus subject areas

Toxicology
Management, Monitoring, Policy and Law
Health, Toxicology and Mutagenesis

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10.1002/tox.22498

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Lin, K. H., Chiu, C. H., Kuo, W. W., Ju, D. T., Shen, C. Y., Chen, R. J., Lin, C. C., Viswanadha, V. P., Liu, J. S., Huang, R. F. S., & Huang, C. Y. (2018). The preventive effects of edible folic acid on cardiomyocyte apoptosis and survival in early onset triple-transgenic Alzheimer's disease model mice. Environmental Toxicology, 33(1), 83-92. https://doi.org/10.1002/tox.22498

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abstract = "In recent years, neuropathological and epidemiological studies have indicated an association between Alzheimer's disease (AD) and several cardiovascular risk factors. In this study, the cardio-protective effects of folic acid (FA) in early stage AD was elucidated using a triple-transgenic (3xTg) Alzheimer's mouse model. Eleven-month-old C57BL/6 mice and 3xTg mice were assigned to five groups. During the four-month treatment period, the low-FA treatment group received FA through their diet, and the high-FA treatment groups received 3 mg/dl folate in drinking water and were also gastric-fed 1.2 mg/kg folate every day. In the C57B1/6J mice, treatment with high doses of FA (HFA) did not show any considerable effect compared to the control group or the low-dose dietary FA treatment group. However, Alzheimer's mice treated with HFA showed enhanced cardio-protection. Western blot analysis revealed that FA treatment restored SIRT1 expression, which was suppressed in 3xTg mice, through enhanced AMPK expression. FA significantly enhanced the IGF1 receptor survival mechanism in the hearts of the 3xTg mice and suppressed the expression-intrinsic and extrinsic apoptosis-associated proteins. The results suggest that FA intake may significantly alleviate cellular pathological events in the heart associated with AD.",

keywords = "Alzheimer's disease, apoptosis, folic acid, preventive effects, survival",

author = "Lin, {Kuan Ho} and Chiu, {Chih Hao} and Kuo, {Wei Wen} and Ju, {Da Tong} and Shen, {Chia Yao} and Chen, {Ray Jade} and Lin, {Chien Chung} and Viswanadha, {Vijaya Padma} and Liu, {Jian Sheng} and Huang, {Rwei Fen S.} and Huang, {Chih Yang}",

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AU - Ju, Da Tong

AU - Shen, Chia Yao

AU - Chen, Ray Jade

AU - Lin, Chien Chung

AU - Viswanadha, Vijaya Padma

AU - Liu, Jian Sheng

AU - Huang, Rwei Fen S.

AU - Huang, Chih Yang

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AB - In recent years, neuropathological and epidemiological studies have indicated an association between Alzheimer's disease (AD) and several cardiovascular risk factors. In this study, the cardio-protective effects of folic acid (FA) in early stage AD was elucidated using a triple-transgenic (3xTg) Alzheimer's mouse model. Eleven-month-old C57BL/6 mice and 3xTg mice were assigned to five groups. During the four-month treatment period, the low-FA treatment group received FA through their diet, and the high-FA treatment groups received 3 mg/dl folate in drinking water and were also gastric-fed 1.2 mg/kg folate every day. In the C57B1/6J mice, treatment with high doses of FA (HFA) did not show any considerable effect compared to the control group or the low-dose dietary FA treatment group. However, Alzheimer's mice treated with HFA showed enhanced cardio-protection. Western blot analysis revealed that FA treatment restored SIRT1 expression, which was suppressed in 3xTg mice, through enhanced AMPK expression. FA significantly enhanced the IGF1 receptor survival mechanism in the hearts of the 3xTg mice and suppressed the expression-intrinsic and extrinsic apoptosis-associated proteins. The results suggest that FA intake may significantly alleviate cellular pathological events in the heart associated with AD.

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The preventive effects of edible folic acid on cardiomyocyte apoptosis and survival in early onset triple-transgenic Alzheimer's disease model mice

Abstract

Keywords

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