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Neuroprotective Effects of Estradiol on Motoneurons in a Model of Rat Spinal Cord Embryonic Explants.
MedLine Citation:
PMID:  23322321     Owner:  NLM     Status:  Publisher    
Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterized by motoneuron death. Clinical and experimental studies in animal models of ALS have found gender differences in the incidence and onset of disease, suggesting that female hormones may play a beneficial role. Cumulative evidence indicates that 17β-estradiol (17βE2) has a neuroprotective role in the central nervous system. We have previously developed a new culture system by using rat spinal cord embryonic explants in which motoneurons have the singularity of migrating outside the spinal cord, growing as a monolayer in the presence of glial cells. In this study, we have validated this new culture system as a useful model for studying neuroprotection by estrogens on spinal cord motoneurons. We show for the first time that spinal cord motoneurons express classical estrogen receptors and that 17βE2 activates, specifically in these cells, the Akt anti-apoptotic signaling pathway and two of their downstream effectors: GSK-3β and Bcl-2. To further validate our system, we demonstrated neuroprotective effects of 17βE2 on spinal cord motoneurons when exposed to the proinflammatory cytokines TNF-α and IFN-γ. These effects of 17βE2 were fully reverted in the presence of the estrogen receptor antagonist ICI 182,780. Our new culture model and the results presented here may provide the basis for further studies on the effects of estrogens, and selective estrogen receptor modulators, on spinal cord motoneurons in the context of ALS or other motoneuron diseases.
Andrea Cardona-Rossinyol; Margalida Mir; Víctor Caraballo-Miralles; Jerònia Lladó; Gabriel Olmos
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-16
Journal Detail:
Title:  Cellular and molecular neurobiology     Volume:  -     ISSN:  1573-6830     ISO Abbreviation:  Cell. Mol. Neurobiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200709     Medline TA:  Cell Mol Neurobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Grup de Neurobiologia Cel·lular, Institut Universitari d'Investigacions en Ciències de la Salut, IUNICS and Departament de Biologia, Universitat de les Illes Balears, Ctra. de Valldemossa km 7.5, Palma de Mallorca, 07122, Spain.
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