Behavioral changes and brain epigenetic alterations induced by maternal deficiencies of B vitamins in a mouse model

Abstract

Rationale

B vitamins play essential roles in brain development and functionality; however, the effects of their deficiency during early life on mental health are not thoroughly understood.

Objectives

The objective of this study is to investigate the effects of a maternal deficiency of vitamin B6, B9 (folate), and B12 on behavioral changes in adult offspring.

Methods

Female C57BL/6 J mice were put on a diet lacking vitamin B6, B9, B12, or the above three vitamins from pregnancy to weaning. The growth and developmental characteristics of both the pregnant mothers and offspring were collected. In the adult offspring, the serum levels of neuroactive substances were measured using an enzyme-linked immunosorbent assay. The level of BDNF and dimethylated lysine 9 on histone H3 (H3K9me2) was detected by immunohistochemical staining. In addition, their depressive-like behaviors, anxiety-like behaviors, and sociability were recorded using sucrose preference, a forced swim, social interaction, tail suspension, and open field tests.

Results

The maternal deficiency of the three B vitamins delayed offspring development. Compared to the controls, all of the groups showed decreased serum levels of 5-HT and neuropeptide Y. In the groups with deficiency of B9 or the three B vitamins, there were significant changes in sociability and social novelty preference. In groups with deficiencies in B9, B12, or all three B vitamins, the expression levels of BDNF and H3K9me2 in the hippocampus were significantly decreased.

Conclusions

Maternal deficiencies of the major B vitamins caused changes in social behaviors in adult mice accompanied with epigenetic alterations in the brain and changes in the serum levels of neuroactive substances.

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Acknowledgments

We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Funding

Funding was provided by National Key R&D Program of China (grant no. 2018YFC1004104), the Guangdong Science and Technology Department Project (grant no. 2019B030316023), and the Key Project of Guangzhou Science and Technology Innovation Committee (grant no. 201804020057).

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Correspondence to Bolan Yu.

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Supplementary information

Figure S1

The immunohistochemical staining analysis of BDNF in five areas of the brain in adult offspring mice. (A) In CA3 area from five groups; (B) in mPFC area from five groups; (C) in NAc area from five groups; (D) in CPu area from five groups; (E) in VTA area from five groups. NOR, group with control diet; DB6, group with vitamin B6–deficient diet; DB9, group with B9-deficient diet; DB12, group with vitamin B12–deficient diet; DB6912, group with vitamin B6–, B9–, and B12–deficient diet. N = 16 mice per group. (PDF 311 kb)

Figure S2

The immunohistochemical staining analysis of H3K9me2 positive cells in five areas of the brain in adult offspring mice. (A) In CA3 area from five groups; (B) in mPFC area from five groups; (C) in NAc area from five groups; (D) in CPu area from five groups; (E) in VTA area from five groups. NOR, group with control diet; DB6, group with vitamin B6–deficient diet; DB9, group with B9–deficient diet; DB12, group with vitamin B12–deficient diet; DB6912, group with vitamin B6–, B9–, and B12–deficient diet. N = 16 mice per group. (PDF 225 kb)

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Xu, P., Pang, D., Zhou, J. et al. Behavioral changes and brain epigenetic alterations induced by maternal deficiencies of B vitamins in a mouse model. Psychopharmacology (2021). https://doi.org/10.1007/s00213-021-05766-2

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Keywords

  • Maternal nutrition
  • B vitamins
  • BDNF
  • H3K9me2