Literature DB >> 22307635

Reduction of dendritic spines and elevation of GABAergic signaling in the brains of mice treated with an estrogen receptor β ligand.

Xin-jie Tan1, Yu-bing Dai, Wan-fu Wu, Hyun-jin Kim, Rodrigo P A Barros, Timothy I Richardson, Benjamin C Yaden, Margaret Warner, David L McKinzie, Venkatesh Krishnan, Jan-Åke Gustafsson.   

Abstract

An estrogen receptor (ER) β ligand (LY3201) with a preference for ERβ over ERα was administered in s.c. pellets releasing 0.04 mg/d. The brains of these mice were examined 3 d after treatment had begun. Although estradiol-17β is known to increase spine density and glutaminergic signaling, as measured by Golgi staining, a clear reduction in spines was evident on the dendritic branches in LY3201-treated mice but no morphological alteration and no difference in the number of dendritic spines on dendritic stems were observed. In the LY3201-treatment group, there was higher expression of glutamic acid decarboxylase (GAD) in layer V of cortex and in the CA1 of hippocampus, more GAD(+) terminals surrounding the pyramidal neurons and less glutamate receptor (NMDAR) on the neurons in layer V. There were no alterations in expression of Iba1 or in Olig2 or CNPase. However, GFAP(+) astrocytes were increased in the LY3201-treatment group. There were also more projections characteristic of activated astrocytes and increased expression of glutamine synthetase (GS). No expression of ERβ was detectable in the nuclei of astrocytes. Clearly, LY3201 caused a shift in the balance between excitatory and inhibitory neurotransmission in favor of inhibition. This shift was due in part to increased synthesis of GABA and increased removal of glutamate from the synaptic cleft by astrocytes. The data reveal that treatment with a selective ERβ agonist results in changes opposite to those reported in estradiol-17β-treated mice and suggests that ERα and ERβ play opposing roles in the brain.

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Year:  2012        PMID: 22307635      PMCID: PMC3277134          DOI: 10.1073/pnas.1121162109

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  43 in total

1.  Estrogen disrupts the inhibition of fear in female rats, possibly through the antagonistic effects of estrogen receptor alpha (ERalpha) and ERbeta.

Authors:  Donna J Toufexis; Karyn M Myers; Michael E Bowser; Michael Davis
Journal:  J Neurosci       Date:  2007-09-05       Impact factor: 6.167

2.  ERbeta-selective estrogen receptor modulators produce antianxiety behavior when administered systemically to ovariectomized rats.

Authors:  Alicia A Walf; Cheryl A Frye
Journal:  Neuropsychopharmacology       Date:  2005-09       Impact factor: 7.853

3.  Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment.

Authors:  Boldizsár Czéh; Jeanine I H Müller-Keuker; Rafal Rygula; Nashat Abumaria; Christoph Hiemke; Enrico Domenici; Eberhard Fuchs
Journal:  Neuropsychopharmacology       Date:  2006-12-13       Impact factor: 7.853

4.  Liver X receptor beta (LXRbeta): a link between beta-sitosterol and amyotrophic lateral sclerosis-Parkinson's dementia.

Authors:  Hyun-Jin Kim; Xiaotang Fan; Chiara Gabbi; Konstantin Yakimchuk; Paolo Parini; Margaret Warner; Jan-Ake Gustafsson
Journal:  Proc Natl Acad Sci U S A       Date:  2008-01-31       Impact factor: 11.205

5.  Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification.

Authors:  Timothy I Richardson; Jeffrey A Dodge; Gregory L Durst; Lance A Pfeifer; Jikesh Shah; Yong Wang; Jim D Durbin; Venkatesh Krishnan; Bryan H Norman
Journal:  Bioorg Med Chem Lett       Date:  2007-06-20       Impact factor: 2.823

6.  Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat.

Authors:  Mounira Banasr; Gerald W Valentine; Xiao-Yuan Li; Shannon L Gourley; Jane R Taylor; Ronald S Duman
Journal:  Biol Psychiatry       Date:  2007-06-21       Impact factor: 13.382

7.  Increased estrogen receptor beta expression correlates with decreased spine formation in the rat hippocampus.

Authors:  Sylwia Szymczak; Katarzyna Kalita; Jacek Jaworski; Basia Mioduszewska; Alena Savonenko; Alicja Markowska; Istvan Merchenthaler; Leszek Kaczmarek
Journal:  Hippocampus       Date:  2006       Impact factor: 3.899

8.  Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice.

Authors:  Cheryl A Frye; Carolyn J Koonce; Kassandra L Edinger; Danielle M Osborne; Alicia A Walf
Journal:  Horm Behav       Date:  2008-08-08       Impact factor: 3.587

9.  Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats.

Authors:  Danielle K Lewis; Adam B Johnson; Shannon Stohlgren; Ashley Harms; Farida Sohrabji
Journal:  J Neuroimmunol       Date:  2008-03-06       Impact factor: 3.478

10.  Estradiol or diarylpropionitrile decrease anxiety-like behavior of wildtype, but not estrogen receptor beta knockout, mice.

Authors:  Alicia A Walf; Carolyn J Koonce; Cheryl A Frye
Journal:  Behav Neurosci       Date:  2008-10       Impact factor: 1.912

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  22 in total

1.  Modulation of higher-primate adrenal androgen secretion with estrogen-alone or estrogen-plus-progesterone intervention.

Authors:  Alan J Conley; Frank Z Stanczyk; John H Morrison; Pawel Borowicz; Kurt Benirschke; Nancy A Gee; Bill L Lasley
Journal:  Menopause       Date:  2013-03       Impact factor: 2.953

Review 2.  The cerebellum as a target for estrogen action.

Authors:  Valerie L Hedges; Timothy J Ebner; Robert L Meisel; Paul G Mermelstein
Journal:  Front Neuroendocrinol       Date:  2012-09-05       Impact factor: 8.606

3.  Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome.

Authors:  Pedro R Olivetti; Atul Maheshwari; Jeffrey L Noebels
Journal:  Sci Transl Med       Date:  2014-01-22       Impact factor: 17.956

4.  Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease.

Authors:  Yu-bing Dai; Xin-jie Tan; Wan-fu Wu; Margaret Warner; Jan-Åke Gustafsson
Journal:  Proc Natl Acad Sci U S A       Date:  2012-07-23       Impact factor: 11.205

5.  Interictal spike frequency varies with ovarian cycle stage in a rat model of epilepsy.

Authors:  James D'Amour; Alejandra Magagna-Poveda; Jillian Moretto; Daniel Friedman; John J LaFrancois; Patrice Pearce; Andre A Fenton; Neil J MacLusky; Helen E Scharfman
Journal:  Exp Neurol       Date:  2015-04-10       Impact factor: 5.330

6.  Mitochondrial estrogen receptor β inhibits cell apoptosis via interaction with Bad in a ligand-independent manner.

Authors:  Jiayi Liang; Qiang Xie; Ping Li; Xueyun Zhong; Yunxian Chen
Journal:  Mol Cell Biochem       Date:  2014-12-19       Impact factor: 3.396

7.  CRH receptor antagonism reverses the effect of social subordination upon central GABAA receptor binding in estradiol-treated ovariectomized female rhesus monkeys.

Authors:  V Michopoulos; M Embree; K Reding; M M Sanchez; D Toufexis; J R Votaw; R J Voll; M M Goodman; J Rivier; M E Wilson; S L Berga
Journal:  Neuroscience       Date:  2013-07-12       Impact factor: 3.590

8.  Liver X receptors regulate cerebrospinal fluid production.

Authors:  Y-B Dai; W-F Wu; B Huang; Y-F Miao; S Nadarshina; M Warner; J-Å Gustafsson
Journal:  Mol Psychiatry       Date:  2015-09-01       Impact factor: 15.992

9.  Targeting estrogen receptor β in microglia and T cells to treat experimental autoimmune encephalomyelitis.

Authors:  Wan-fu Wu; Xin-jie Tan; Yu-bing Dai; Venkatesh Krishnan; Margaret Warner; Jan-Åke Gustafsson
Journal:  Proc Natl Acad Sci U S A       Date:  2013-02-11       Impact factor: 11.205

Review 10.  Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential.

Authors:  Ilaria Paterni; Carlotta Granchi; John A Katzenellenbogen; Filippo Minutolo
Journal:  Steroids       Date:  2014-06-24       Impact factor: 2.668

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