Hippocampal gene expression is highly responsive to estradiol replacement in middle-aged female rats

Miklós Sárvári, I. Kalló, E. Hrabovszky, N. Solymosi, Annie Rodolosse, Csaba Vastagh, Herbert Auer, Z. Liposits

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

In the hippocampus, estrogens are powerful modulators of neurotransmission, synaptic plasticity and neurogenesis. In women, menopause is associated with increased risk of memory disturbances, which can be attenuated by timely estrogen therapy. In animal models of menopause, 17β-estradiol (E2) replacement improves hippocampus-dependent spatial memory. Here, we explored the effect of E2 replacement on hippocampal gene expression in a rat menopause model. Middle-aged ovariectomized female rats were treated continuously for 29 days with E2, and then, the hippocampal transcriptome was investigated with Affymetrix expression arrays. Microarray data were analyzed by Bioconductor packages and web-based softwares, and verified with quantitative PCR. At standard fold change selection criterion, 156 genes responded to E2. All alterations but 4 were transcriptional activation. Robust activation (fold change > 10) occurred in the case of transthyretin, klotho, claudin 2, prolactin receptor, ectodin, coagulation factor V, Igf2, Igfbp2, and sodium/sulfate symporter. Classification of the 156 genes revealed major groups, including signaling (35 genes), metabolism (31 genes), extracellular matrix (17 genes), and transcription (16 genes). We selected 33 genes for further studies, and all changes were confirmed by real-time PCR. The results suggest that E2 promotes retinoid, growth factor, homeoprotein, neurohormone, and neurotransmitter signaling, changes metabolism, extracellular matrix composition, and transcription, and induces protective mechanisms via genomic effects. We propose that these mechanisms contribute to effects of E2 on neurogenesis, neural plasticity, and memory functions. Our findings provide further support for the rationale to develop safe estrogen receptor ligands for the maintenance of cognitive performance in postmenopausal women.

Original languageEnglish
Pages (from-to)2632-2645
Number of pages14
JournalEndocrinology
Volume156
Issue number7
DOIs
Publication statusPublished - Jul 1 2015

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Estradiol
Gene Expression
Genes
Menopause
Neuronal Plasticity
Neurogenesis
Extracellular Matrix
Neurotransmitter Agents
Hippocampus
Estrogens
Claudin-2
Prolactin Receptors
Symporters
Homeodomain Proteins
Prealbumin
Factor V
Retinoids
Transcriptome
Synaptic Transmission
Estrogen Receptors

ASJC Scopus subject areas

  • Endocrinology

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Hippocampal gene expression is highly responsive to estradiol replacement in middle-aged female rats. / Sárvári, Miklós; Kalló, I.; Hrabovszky, E.; Solymosi, N.; Rodolosse, Annie; Vastagh, Csaba; Auer, Herbert; Liposits, Z.

In: Endocrinology, Vol. 156, No. 7, 01.07.2015, p. 2632-2645.

Research output: Contribution to journalArticle

Sárvári, Miklós ; Kalló, I. ; Hrabovszky, E. ; Solymosi, N. ; Rodolosse, Annie ; Vastagh, Csaba ; Auer, Herbert ; Liposits, Z. / Hippocampal gene expression is highly responsive to estradiol replacement in middle-aged female rats. In: Endocrinology. 2015 ; Vol. 156, No. 7. pp. 2632-2645.
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