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Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats

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Abstract

Previous studies showed that neonatal dexamethasone treatment (NDT) transiently impaired hippocampal function in male rats. Hippocampal estrogen receptors (ERs) participate in avoidance learning. As previous studies focused on males only, this study was aimed to investigate the NDT effects on the hippocampal function of female rats. Newborn Wistar female rats were subjected to a tapering dose of dexamethasone (0.5 mg, 0.3 mg, and 0.1 mg/kg, subcutaneously) from postnatal days 1 to 3 and were subjected to experiments at the age of 6 weeks (adolescence). Brain slice extracellular recording and the inhibitory avoidance (IA) test were used to evaluate the NDT effects on hippocampal function. The results showed that NDT completely blocked the hippocampal long-term potentiation (LTP) formation and IA learning of adolescents. The expression of hippocampal estrogen receptor alpha (ERα) was attenuated in NDT subjects. Reduced histone acetylation of the ERα gene was found, possibly explaining the reduced hippocampal ERα expression in NDT female rats. Suprafusion of estradiol (E2) partially restored the hippocampal LTP formation in adolescent NDT female rats. Coadministration of the histone deacetylase inhibitor trichostatin-A restored the hippocampal ERα expression, hippocampal LTP formation, and IA learning in adolescent NDT female rats. Collectively, these results suggested that NDT has an epigenetic modulation effect on the expression of hippocampal ERα, which is responsible for its adverse effect on hippocampal function.

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Acknowledgments

We thank the Academic Paper Editing Clinic, National Taiwan Normal University (APEC of NTNU).

Funding

This study was supported by the Ministry of Science and Technology (MOST), Taiwan (103-2320-B-003-002 and 104-2320-B-003-00).

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Authors and Affiliations

  1. Department of Life Science, National Taiwan Normal University, Taipei, Taiwan

    Hui-Fang Chiu, Chiung-Yin Cheng & Kwok-Tung Lu

  2. Department of Life Science, National Chung Cheng University, Chia-Yi, Taiwan

    Michael W. Y. Chan & Jora Meng-Ju Lin

  3. Division of Gastroenterology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan

    Jian-Liang Chou

  4. Institute of Biochemical Science and Technology, National Chia-Yi University, Chia-Yi, Taiwan

    Yi-Ling Yang

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  1. Hui-Fang Chiu
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Contributions

KTL and YLY participated in the conception and design. CYC contributed to the electrophysiological experiments. HFC, MWYC, JLC, and JMJL participated in the ChIP experiment. HFC collected and assembled the data. HFC, MWYC, KTL, and YLY analyzed and interpreted the data. KTL and YLY wrote the manuscript and provided financial support. All authors corrected and approved the manuscript.

Corresponding authors

Correspondence to Yi-Ling Yang or Kwok-Tung Lu.

Ethics declarations

All procedures were conducted in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals and were approved by the local Institutional animal Care and Use Committee (IACUC) at the National Taiwan Normal University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Chiu, HF., Chan, M.W.Y., Cheng, CY. et al. Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats. Mol Neurobiol 56, 2224–2233 (2019). https://doi.org/10.1007/s12035-018-1214-6

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  • DOI: https://doi.org/10.1007/s12035-018-1214-6

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