Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns

ABSTRACT

Objective

To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

Methods

Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45β, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR.

Results

Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group.

Conclusion

Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

KEYWORDS:

• BDNF gene expression
• DNA methylation
• early-life
• learning and memory
• zinc deficiency
• offspring
• hippocampus
• zinc status

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

All animal studies conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health. This experiment was performed in accordance with Tianjin Institute of Environmental and Operational Medicine Animal Care and Use Committee, with the reference number SCXK/2014/0001.

Additional information

Funding

This work was supported by the National Nature Science Foundation of Tianjin [grant number 15JCYBJC27100] and the National Nature Science Foundation of China [grant number 30872098].