| First Author | Tan XJ | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 5 | Pages | 1708-12 |
| PubMed ID | 22307635 | Mgi Jnum | J:182030 |
| Mgi Id | MGI:5314592 | Doi | 10.1073/pnas.1121162109 |
| Citation | Tan XJ, et al. (2012) Reduction of dendritic spines and elevation of GABAergic signaling in the brains of mice treated with an estrogen receptor beta ligand. Proc Natl Acad Sci U S A 109(5):1708-12 |
| abstractText | An estrogen receptor (ER) beta ligand (LY3201) with a preference for ERbeta over ERalpha 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-17beta 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 ERbeta 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 ERbeta agonist results in changes opposite to those reported in estradiol-17beta-treated mice and suggests that ERalpha and ERbeta play opposing roles in the brain. |
