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

Hui Fang Chiu; Michael W.Y. Chan; Chiung Yin Cheng; Jian Liang Chou; Jora Meng Ju Lin; Yi Ling Yang; Kwok Tung Lu

doi:10.1007/s12035-018-1214-6

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

Hui Fang Chiu, Michael W.Y. Chan, Chiung Yin Cheng, Jian Liang Chou, Jora Meng Ju Lin, Yi Ling Yang, Kwok Tung Lu^*

^*Corresponding author for this work

Department of Life Science

Research output: Contribution to journal › Article › peer-review

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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 (E ₂ ) 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.

Original language	English
Pages (from-to)	2224-2233
Number of pages	10
Journal	Molecular Neurobiology
Volume	56
Issue number	3
DOIs	https://doi.org/10.1007/s12035-018-1214-6
Publication status	Published - 2019 Mar 1

Keywords

Dexamethasone
Estrogen receptor α
Hippocampus
Neonatal

ASJC Scopus subject areas

Neurology
Cellular and Molecular Neuroscience

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10.1007/s12035-018-1214-6

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title = "Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats",

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 (E 2 ) 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.",

keywords = "Dexamethasone, Estrogen receptor α, Hippocampus, Neonatal",

author = "Chiu, {Hui Fang} and Chan, {Michael W.Y.} and Cheng, {Chiung Yin} and Chou, {Jian Liang} and Lin, {Jora Meng Ju} and Yang, {Yi Ling} and Lu, {Kwok Tung}",

note = "Publisher Copyright: {\textcopyright} 2018, Springer Science+Business Media, LLC, part of Springer Nature.",

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doi = "10.1007/s12035-018-1214-6",

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AU - Chiu, Hui Fang

AU - Chan, Michael W.Y.

AU - Cheng, Chiung Yin

AU - Chou, Jian Liang

AU - Lin, Jora Meng Ju

AU - Yang, Yi Ling

AU - Lu, Kwok Tung

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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 (E 2 ) 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.

AB - 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 (E 2 ) 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.

KW - Dexamethasone

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

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