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Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice

  • Authors:
    • Wanxiao Sun
    • Qiting Qing
    • Xu Cheng
    • Jing Chen
    • Ningning Yu
    • Liyuan Zhu
    • Mei Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Basic Nursing, School of Nursing, Anhui Medical University, Hefei, Anhui 230032, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 206
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    Published online on: January 7, 2022
       https://doi.org/10.3892/etm.2022.11129
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Abstract

Although previous studies have reported that serum folate levels are negatively associated with depression in women but not men, it remains unclear whether folate deficiency can directly lead to depression and whether sex difference serves a role in this condition, since the potential mechanism remains elusive. Therefore, the present study aimed to investigate whether folate deficiency results in differences in parameters associated with depression between males and females. CD‑1 mice received either a standard control diet or a folate‑deficient diet from 10 to 38 weeks of age, following which behavioral assays, such as an open field test, sucrose preference test and forced swim test were performed throughout week 38. Serum and cerebral cortex samples were subsequently collected for assessment. Serum folate, homocysteine, estradiol (E2) and testosterone levels were measured using chemiluminescence, enzymatic cycling assay and electrochemiluminescence immunoassays. The cerebral cortex was used for western blot analysis, to detect the expression levels of estrogen receptor β (ERβ), PI3K/AKT pathway and caspase‑3. The results revealed that compared with those in female mice that received standard control diet, female mice that received folate‑deficient diet exhibited lower E2 concentrations, lower sucrose preferences (as determined through the sucrose preference test), longer durations of immobility (as determined in the forced swim test) and less time spent in the central areas of the open field test. Western blotting demonstrated that the expression levels of ERβ and the phosphorylation levels of PI3K and AKT were decreased, whilst the expression levels of cleaved caspase‑3 were increased, in the cerebral cortex of female mice that received folate‑deficient diet. However, no differences in E2 concentration, behavioral assay parameters or protein levels of ERβ, phosphorylated (p‑)PI3K, p‑AKT and cleaved caspase‑3 could be observed in male mice regardless of whether they received standard control or folate‑deficient diets. Collectively, these results revealed that folate deficiency only led to depression‑like behavior in female mice. This may be associated with reduced E2 levels, which may inhibit the PI3K/AKT pathway and upregulate the expression of cleaved caspase‑3 to promote neuronal apoptosis.
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Copy and paste a formatted citation
Spandidos Publications style
Sun W, Qing Q, Cheng X, Chen J, Yu N, Zhu L and Zhao M: Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice. Exp Ther Med 23: 206, 2022.
APA
Sun, W., Qing, Q., Cheng, X., Chen, J., Yu, N., Zhu, L., & Zhao, M. (2022). Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice. Experimental and Therapeutic Medicine, 23, 206. https://doi.org/10.3892/etm.2022.11129
MLA
Sun, W., Qing, Q., Cheng, X., Chen, J., Yu, N., Zhu, L., Zhao, M."Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice". Experimental and Therapeutic Medicine 23.3 (2022): 206.
Chicago
Sun, W., Qing, Q., Cheng, X., Chen, J., Yu, N., Zhu, L., Zhao, M."Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice". Experimental and Therapeutic Medicine 23, no. 3 (2022): 206. https://doi.org/10.3892/etm.2022.11129
Copy and paste a formatted citation
x
Spandidos Publications style
Sun W, Qing Q, Cheng X, Chen J, Yu N, Zhu L and Zhao M: Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice. Exp Ther Med 23: 206, 2022.
APA
Sun, W., Qing, Q., Cheng, X., Chen, J., Yu, N., Zhu, L., & Zhao, M. (2022). Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice. Experimental and Therapeutic Medicine, 23, 206. https://doi.org/10.3892/etm.2022.11129
MLA
Sun, W., Qing, Q., Cheng, X., Chen, J., Yu, N., Zhu, L., Zhao, M."Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice". Experimental and Therapeutic Medicine 23.3 (2022): 206.
Chicago
Sun, W., Qing, Q., Cheng, X., Chen, J., Yu, N., Zhu, L., Zhao, M."Effects of chronic folate deficiency and sex differences on depression‑like behavior in mice". Experimental and Therapeutic Medicine 23, no. 3 (2022): 206. https://doi.org/10.3892/etm.2022.11129
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