Hdl Handle:
http://hdl.handle.net/10675.2/51
Title:
Estrogen-astrocyte interactions: implications for neuroprotection.
Authors:
Dhandapani, Krishnan M.; Brann, Darrell W ( 0000-0002-4480-8859 )
Abstract:
BACKGROUND: Recent work has suggested that the ovarian steroid 17beta-estradiol, at physiological concentrations, may exert protective effects in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and acute ischemic stroke. While physiological concentrations of estrogen have consistently been shown to be protective in vivo, direct protection upon purified neurons is controversial, with many investigators unable to show a direct protection in highly purified primary neuronal cultures. These findings suggest that while direct protection may occur in some instances, an alternative or parallel pathway for protection may exist which could involve another cell type in the brain. PRESENTATION OF THE HYPOTHESIS: A hypothetical indirect protective mechanism is proposed whereby physiological levels of estrogen stimulate the release of astrocyte-derived neuroprotective factors, which aid in the protection of neurons from cell death. This hypothesis is attractive as it provides a potential mechanism for protection of estrogen receptor (ER)-negative neurons through an astrocyte intermediate. It is envisioned that the indirect pathway could act in concert with the direct pathway to achieve a more widespread global protection of both ER+ and ER- neurons. TESTING THE HYPOTHESIS: We hypothesize that targeted deletion of estrogen receptors in astrocytes will significantly attenuate the neuroprotective effects of estrogen. IMPLICATIONS OF THE HYPOTHESIS: If true, the hypothesis would significantly advance our understanding of endocrine-glia-neuron interactions. It may also help explain, at least in part, the reported beneficial effects of estrogen in neurodegenerative disorders. Finally, it also sets the stage for potential extension of the hypothetical mechanism to other important estrogen actions in the brain such as neurotropism, neurosecretion, and synaptic plasticity.
Citation:
BMC Neurosci. 2002 Jun 7; 3:6
Issue Date:
31-Mar-2003
URI:
http://hdl.handle.net/10675.2/51
PubMed ID:
12067420
PubMed Central ID:
PMC116596
Type:
Journal Article; Research Support, U.S. Gov't, P.H.S.
ISSN:
1471-2202
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorDhandapani, Krishnan M.en_US
dc.contributor.authorBrann, Darrell Wen_US
dc.date.accessioned2010-09-24T21:26:47Z-
dc.date.available2010-09-24T21:26:47Z-
dc.date.issued2003-03-31en_US
dc.identifier.citationBMC Neurosci. 2002 Jun 7; 3:6en_US
dc.identifier.issn1471-2202en_US
dc.identifier.pmid12067420en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/51-
dc.description.abstractBACKGROUND: Recent work has suggested that the ovarian steroid 17beta-estradiol, at physiological concentrations, may exert protective effects in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and acute ischemic stroke. While physiological concentrations of estrogen have consistently been shown to be protective in vivo, direct protection upon purified neurons is controversial, with many investigators unable to show a direct protection in highly purified primary neuronal cultures. These findings suggest that while direct protection may occur in some instances, an alternative or parallel pathway for protection may exist which could involve another cell type in the brain. PRESENTATION OF THE HYPOTHESIS: A hypothetical indirect protective mechanism is proposed whereby physiological levels of estrogen stimulate the release of astrocyte-derived neuroprotective factors, which aid in the protection of neurons from cell death. This hypothesis is attractive as it provides a potential mechanism for protection of estrogen receptor (ER)-negative neurons through an astrocyte intermediate. It is envisioned that the indirect pathway could act in concert with the direct pathway to achieve a more widespread global protection of both ER+ and ER- neurons. TESTING THE HYPOTHESIS: We hypothesize that targeted deletion of estrogen receptors in astrocytes will significantly attenuate the neuroprotective effects of estrogen. IMPLICATIONS OF THE HYPOTHESIS: If true, the hypothesis would significantly advance our understanding of endocrine-glia-neuron interactions. It may also help explain, at least in part, the reported beneficial effects of estrogen in neurodegenerative disorders. Finally, it also sets the stage for potential extension of the hypothetical mechanism to other important estrogen actions in the brain such as neurotropism, neurosecretion, and synaptic plasticity.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshAstrocytes / drug effects / physiologyen_US
dc.subject.meshBrain Ischemia / drug therapyen_US
dc.subject.meshCell Communication / drug effects / physiologyen_US
dc.subject.meshEstradiol / pharmacology / physiologyen_US
dc.subject.meshEstrogen Receptor alphaen_US
dc.subject.meshEstrogen Receptor betaen_US
dc.subject.meshEstrogens / pharmacology / physiologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshModels, Theoreticalen_US
dc.subject.meshNeurons / drug effects / physiologyen_US
dc.subject.meshNeuroprotective Agents / pharmacologyen_US
dc.subject.meshReceptors, Estrogen / deficiency / metabolismen_US
dc.subject.meshRodentiaen_US
dc.subject.meshSignal Transduction / physiologyen_US
dc.titleEstrogen-astrocyte interactions: implications for neuroprotection.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, U.S. Gov't, P.H.S.en_US
dc.identifier.pmcidPMC116596en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Geneticsen_US
dc.contributor.corporatenameDepartment of Neurologyen_US

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