Estrogen receptor-dependent regulation of sensory neuron survival in developing dorsal root ganglion.
Estrogen is known to influence different functions in brain tissue ranging from neuronal development to plasticity and survival, but the mechanisms involved have not been defined clearly. Previous studies have shown the presence of the two estrogen receptors (ERs), ERalpha and ERbeta, in several brain areas, but less is known about the role of estrogen in the peripheral nervous system. Here we demonstrate that dorsal root ganglion (DRG) neurons express ERalpha and ERbeta during early postnatal development and in culture, and that the ERs localize mainly to neuronal cell nuclei. Studying the role of estrogen in DRG, we observed that low concentrations of 17beta-estradiol increased survival of cultured DRG neurons deprived of nerve growth factor. 17beta-Estradiol up-regulated the expression of the antiapoptotic molecule Bcl-x without affecting that of Bax, suggesting a mechanism by which the hormone counteracted neuronal death. Antiestrogens abolished the action of 17beta-estradiol in the DRG neurons, which demonstrates an involvement of ERs. The results show that estrogen and ERs play an important role in the development and survival of DRG neurons.
Patrone
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C
Department of Neuroscience, Neurobiology, Uppsala University, Biomedical Center, Box 587, S-75123 Uppsala, Sweden.
Andersson
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S
Korhonen
L
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Lindholm
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D
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005727:Ganglia, Spinal / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D009414:Nerve Growth Factors / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D004958:Estradiol