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Accelerated reduction of serum thyroxine and hippocampal histone acetylation links to exacerbation of spatial memory impairment in aged CD-1 mice pubertally exposed to bisphenol-a

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Abstract

Age-related cognitive decline has been associated with changes in endogenous hormones and epigenetic modification of chromatin, including histone acetylation. Developmental exposure to endocrine disrupting chemicals, such as bisphenol-A (BPA) that produces endocrine disruption and epigenetic changes, may be a risk factor for accelerating cognitive deficits during aging. Thus, we exposed CD-1 mice to BPA (0, 1, and 100 mg/l BPA in the drinking water) orally during puberty (from postnatal days 28 to 56) and investigated whether pubertal BPA exposure exacerbates the age-related impairment of spatial cognition in old age (18 months old) and whether serum sex and thyroid hormones or hippocampal histone acetylation (H3K9ac and H4K8ac) are associated with cognitive effects. A young control group (6 months old) was added to analyze the age effect. Results showed untreated aged mice had marked decline of spatial learning and memory in the novel location recognition and radial six-arm water maze tasks, with decreased levels of these hormones and hippocampal H3K9ac and H4K8ac compared to young controls. The BPA treatment exacerbated age-related spatial cognitive impairment and accelerated the reduction of free thyroxine (FT4), H3K9ac, and H4K8ac, and the 100 mg/l BPA group showed more significant impact. Additionally, correlation analyses revealed that lower levels of FT4, H3K9ac, and H4K8ac were accompanied by decreased spatial memory abilities. We concluded that accelerated reduction of serum FT4 and hippocampal H3K9ac and H4K8ac might be linked to exacerbation of age-related spatial cognitive impairment due to pubertal BPA exposure.

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Acknowledgments

This study was financially supported by the National Foundation of Nature Science of China (81370444), the Natural Science Foundation for the Youth of China (81301094), the College Science Foundation of Anhui Medical University (2015xkj024), and the College Natural Science Foundation of Anhui province (KJ2016A319).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, People’s Republic of China

    Wei Jiang, Fang Wang, Hai Ge, Peng-Chao Wu, Xue-Wei Li & Gui-Hai Chen

  2. Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui Province, People’s Republic of China

    Lei Cao

  3. Departments of Neurology and General Practice, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Hefei, 238000, Anhui Province, People’s Republic of China

    Gui-Hai Chen

  4. Psychologic Medicine Center of Anhui Medical University, Chaohu, Hefei, 238000, Anhui Province, People’s Republic of China

    Gui-Hai Chen

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  1. Wei Jiang
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Wei Jiang and Lei Cao contributed equally to this work

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Jiang, W., Cao, L., Wang, F. et al. Accelerated reduction of serum thyroxine and hippocampal histone acetylation links to exacerbation of spatial memory impairment in aged CD-1 mice pubertally exposed to bisphenol-a. AGE 38, 405–418 (2016). https://doi.org/10.1007/s11357-016-9947-5

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