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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)2224-2233
Number of pages10
JournalMolecular Neurobiology
Volume56
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

Fingerprint

Estrogen Receptors
Dexamethasone
Avoidance Learning
Long-Term Potentiation
Therapeutics
trichostatin A
Histone Deacetylase Inhibitors
Estrogen Receptor alpha
Acetylation
Epigenomics
Histones
Wistar Rats
Estradiol
Brain

Keywords

  • Dexamethasone
  • Estrogen receptor α
  • Hippocampus
  • Neonatal

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats. / Chiu, Hui Fang; Chan, Michael W.Y.; Cheng, Chiung Yin; Chou, Jian Liang; Lin, Jora Meng Ju; Yang, Yi Ling; Lu, Kwok Tung.

In: Molecular Neurobiology, Vol. 56, No. 3, 01.03.2019, p. 2224-2233.

Research output: Contribution to journalArticle

Chiu, Hui Fang ; Chan, Michael W.Y. ; Cheng, Chiung Yin ; Chou, Jian Liang ; Lin, Jora Meng Ju ; Yang, Yi Ling ; Lu, Kwok Tung. / Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats. In: Molecular Neurobiology. 2019 ; Vol. 56, No. 3. pp. 2224-2233.
@article{097e8ab7e7f84afe9250f9970651b8e4,
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}",
year = "2019",
month = "3",
day = "1",
doi = "10.1007/s12035-018-1214-6",
language = "English",
volume = "56",
pages = "2224--2233",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "3",

}

TY - JOUR

T1 - Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats

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

KW - Estrogen receptor α

KW - Hippocampus

KW - Neonatal

UR - http://www.scopus.com/inward/record.url?scp=85049879606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049879606&partnerID=8YFLogxK

U2 - 10.1007/s12035-018-1214-6

DO - 10.1007/s12035-018-1214-6

M3 - Article

VL - 56

SP - 2224

EP - 2233

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 3

ER -