Morphological Effects of Estrogen on Cholinergic Neurons<i>In Vitro</i>Involves Activation of Extracellular Signal-Regulated Kinases

Dominguez, Reymundo; Jalali, Cathy; Lacalle, Sonsoles de

doi:10.1523/jneurosci.2586-03.2004

Cited by 56 publications

(38 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These so-called nongenomic effects include activation of cell signaling molecules such as protein kinases. In several models, the neurotropic and neuroprotective effects of estrogen have been linked to a rapid stimulation of the mitogen activated protein kinase (MAPK) pathway and/or the phosphoinositol 3-kinase (PI3K) pathway (Singer et al 1999, Kuroki et al 2001, Zhang et al 2001, Fitzpatrick et al 2002, Mize et al 2003, Dominguez et al 2004. Such rapid nongenomic effects could potentially promote differentiating and protective effects of estrogens in PC12 ER cells.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor

Mérot¹,

Ferrière²,

Debroas³

et al. 2005

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Numerous studies, both in vivo and in vitro, have reported neuronal differentiating and neuroprotective actions of estrogens. Most of these estrogenic effects are mediated through specific receptors termed estrogen receptors. The aim of this study was to assess the importance of the N-terminal A/B domain of the estrogen receptor-alpha (ER ) in its neuronal aspects. Consequently, estrogen effects on (i) the transcriptional activity of target genes, (ii) neuronal differentiation and (iii) neuroprotection in PC12 cells transfected with either a full length form of ER or an A/B domain truncated form (ER CF), have been studied. We demonstrate that the maximal estrogen-induced transcriptional activity of reporter genes requires a full length ER , especially when cells are differentiated. Precisely, the transcriptional activity of ER in differentiated cells relies, predominantly, on the activation function AF-1, located in the A/B domain. Furthermore, in PC12 cells stably expressing ER , 17 -estradiol markedly enhances the neurite outgrowth triggered by treatment with nerve growth factor and protects cells from oxidative shocks induced by depletion of glutathione. These estrogenic effects are not observed in non-transfected cells and in cells transfected with the truncated ER, devoid of the A/B domain. Altogether, these results underline the importance of the A/B domain of ER in both the differentiating and the neuroprotective effects of estrogens.

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor

Mérot¹,

Ferrière²,

Debroas³

et al. 2005

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…Some of the known intrinsic factors are calcium/calmodulin-dependent protein kinase II (Fink et al, 2003); the small GTPases RhoA, Rac1, and Cdc42 (Threadgill et al, 1997;Ruchhoeft et al, 1999;Li et al, 2000); novel genes identified in Drosophila (Gao et al, 1999;Moore et al, 2002;Grueber et al, 2003;Yu and Malenka, 2003;Emoto et al, 2004); ␤-catenin (Yu and Malenka, 2003); Dishevelled (Rosso et al, 2005); a calcium-responsive transactivator called CREST (Aizawa et al, 2004); and cypin (cytosolic PSD-95 interactor; Firestein et al, 1999;Akum et al, 2004). The external factors comprise a long list and include neurotrophins (McAllister et al, 1995;McAllister et al, 1997;Baker et al, 1998;Horch et al, 1999;Lom and Cohen-Cory, 1999), electrical activity (McAllister et al, 1996;Cambiasso et al, 2000;Vaillant et al, 2002;Yu and Malenka, 2003), and estrogen (Cambiasso et al, 2000;Audesirk et al, 2003a,b;Sakamoto et al, 2003;Dominguez et al, 2004;Nathan et al, 2004). As of yet, there have been only a small number of studies that examine how the extracellular and intrinsic factors are linked to determine dendrite morphology.…”

Section: Introductionmentioning

confidence: 99%

A Novel Role for Snapin in Dendrite Patterning: Interaction with Cypin

Chen

Lucas

Akum

et al. 2005

MBoC

View full text Add to dashboard Cite

Temporal and spatial assembly of signal transduction machinery determines dendrite branch patterning, a process crucial for proper synaptic transmission. Our laboratory previously cloned and characterized cypin, a protein that decreases PSD-95 family member localization and regulates dendrite number. Cypin contains zinc binding, collapsin response mediator protein (CRMP) homology, and PSD-95, Discs large, zona occludens-1 binding domains. Both the zinc binding and CRMP homology domains are needed for dendrite patterning. In addition, cypin binds tubulin via its CRMP homology domain to promote microtubule assembly. Using a yeast two-hybrid screen of a rat brain cDNA library with cypin lacking the carboxyl terminal eight amino acids as bait, we identified snapin as a cypin binding partner. Here, we show by affinity chromatography and coimmunoprecipitation that the carboxyl-terminal coiled-coil domain (H2) of snapin is required for cypin binding. In addition, snapin binds to cypin's CRMP homology domain, which is where tubulin binds. We also show that snapin competes with tubulin for binding to cypin, resulting in decreased microtubule assembly. Subsequently, overexpression of snapin in primary cultures of hippocampal neurons results in decreased primary dendrites present on these neurons and increased probability of branching. Together, our data suggest that snapin regulates dendrite number in developing neurons by modulating cypin-promoted microtubule assembly.

show abstract

“…Estrogen has also been shown to act as a trophic factor promoting the growth and arborization of axons and dendrites in culture (17)(18)(19), as well as promoting synapse/spine formation (20 -26). In addition, estrogen also regulates the transcription of key enzymes involved in the synthesis and turnover of classic neurotransmitters including noradrenaline, dopamine, serotonin, and acetylcholine (27)(28)(29)(30), as well as the transcription of neurotrophins; neuropeptides, including vasopressin and insulin-like growth factor (31)(32)(33)(34); and cell surface receptors such as oxytocin receptor (35).…”

mentioning

confidence: 99%

Transcriptional Interaction of an Estrogen Receptor Splice Variant and ErbB4 Suggests Convergence in Gene Susceptibility Pathways in Schizophrenia

Wong

Weickert

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Mounting evidence from clinical and basic research suggests that estrogen signaling may be altered in the brains of people with schizophrenia. Previously, we found that DNA sequence variation in the estrogen receptor (ER) ␣ gene, lower ER␣ mRNA levels, and/or blunted ER␣ signaling is associated with schizophrenia. In this study, we asked whether the naturally occurring truncated ER␣ isoform, ⌬7, which acts as a dominant negative, can attenuate gene expression induced by the wildtype (WT) receptor in an estrogen-dependent manner in neuronal (SHSY5Y) and non-neuronal (CHOK1 and HeLa) cells. In addition, we determined the extent to which ER␣ interacts with NRG1-ErbB4, a leading schizophrenia susceptibility pathway. Reductions in the transcriptionally active form of ErbB4 comprising the intracytoplasmic domain (ErbB4-ICD) have been found in schizophrenia, and we hypothesized that ER␣ and ErbB4 may converge to control gene expression. In the present study, we show that truncated ⌬7-ER␣ attenuates WT-ER␣-driven gene expression across a wide range of estrogen concentrations in cells that express functional ER␣ at base line or upon co-transfection of full-length ER␣. Furthermore, we find that ErbB4-ICD can potentiate the transcriptional activity of WT-ER␣ at EREs in two cell lines and that this potentiation effect is abolished by the presence of ⌬7-ER␣. Immunofluorescence microscopy revealed nuclear co-localization of WT-ER␣, ⌬7-ER␣, and ErbB4-ICD, whereas immunoprecipitation assays showed direct interaction. Our findings demonstrate convergence between ER␣ and ErbB4-ICD in the transcriptional control of ER␣-target gene expression and suggest that this may represent a convergent pathway that may be disrupted in schizophrenia.Schizophrenia is a devastating mental illness of unknown cause, afflicting 1% of the population worldwide. At present, the molecular processes underlying the development and progression of schizophrenia have not been clearly identified; however, we have recently found evidence to support the hypothesis that schizophrenia arises from a derailment of normal brain maturation during adolescence where the brain fails to respond to the developmental increase in sex steroids (testosterone and estrogen) (1). Testosterone is commonly converted into estrogen by the action of the enzyme aromatase whereby the converted hormone serves as a ligand for estrogen receptors. Schizophrenia affects both men and women occurring at a ratio of ϳ3:2, respectively (2). Males typically have an earlier age of onset and more severe symptoms and tend to be less treatment responsive than females with schizophrenia (3). However, women with schizophrenia can have symptom exacerbation at times of low estrogen: during post-partum and menopause (4 -6), and schizophrenic symptoms can be ameliorated with estrogen treatment (7-11).Estrogen affects the developing brain by influencing the genesis, development, migration, plasticity, and survival of neurons (12-16). Estrogen has also been shown to act as a trophic factor promoting the grow...

show abstract

Morphological Effects of Estrogen on Cholinergic NeuronsIn VitroInvolves Activation of Extracellular Signal-Regulated Kinases

Cited by 56 publications

References 79 publications

Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor

Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor

A Novel Role for Snapin in Dendrite Patterning: Interaction with Cypin

Transcriptional Interaction of an Estrogen Receptor Splice Variant and ErbB4 Suggests Convergence in Gene Susceptibility Pathways in Schizophrenia

Contact Info

Product

Resources

About