Abstract:
:The higher prevalence and risk for Alzheimer's disease in women relative to men has been partially attributed to the precipitous decline in gonadal hormone levels that occurs in women following the menopause. Although considerable attention has been focused on the consequence of estrogen loss, and thus estrogen's neuroprotective potential, it is important to recognize that the menopause results in a precipitous decline in progesterone levels as well. In fact, progesterone is neuroprotective, although the precise mechanisms involved remain unclear. Based on our previous observation that progesterone elicits the phosphorylation of ERK and Akt, key effectors of the neuroprotective mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3-K) pathways, respectively, we determined whether activation of either of these pathways was necessary for progesterone-induced protection. With organotypic explants (slice culture) of the cerebral cortex, we found that progesterone protected against glutamate-induced toxicity. Furthermore, these protective effects were inhibited by either the MEK1/2 inhibitor UO126 or the PI3-K inhibitor LY294002, supporting the requirement for both the MAPK and PI3-K pathways in progesterone-induced protection. In addition, at a concentration and duration of treatment consistent with our neuroprotection data, progesterone also increased the expression of brain-derived neurotrophic factor (BDNF), at the level of both protein and mRNA. This induction of BDNF may be relevant to the protective effects of progesterone, in that inhibition of Trk signaling, with K252a, inhibited the protective effects of progesterone. Collectively, these data suggest that progesterone is protective via multiple and potentially related mechanisms. (c) 2007 Wiley-Liss, Inc.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Kaur P,Jodhka PK,Underwood WA,Bowles CA,de Fiebre NC,de Fiebre CM,Singh Mdoi
10.1002/jnr.21370subject
Has Abstractpub_date
2007-08-15 00:00:00pages
2441-9issue
11eissn
0360-4012issn
1097-4547journal_volume
85pub_type
杂志文章abstract::It is generally recognized that lipid peroxides play an important role in the pathogenesis of several diseases and that sulfhydryl groups are critically involved in cellular defense against endogenous or exogenous oxidants. Recent evidence indicates that lipid peroxides directly participate in induction of cytoprotect...
journal_title:Journal of neuroscience research
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doi:10.1002/jnr.10177
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abstract::Contrary to widely held beliefs, the gene encoding proteolipid protein (PLP), the major structural protein of central nervous system myelin, is expressed in Schwann cells and their tumors. Proteolipid mRNA was identified in human acoustic neuromas and in rat and rabbit sciatic nerves using a human PLP cDNA as a probe....
journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490060403
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20439
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490270426
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490060205
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4547(19981201)54:5<691::AID-JNR
更新日期:1998-12-01 00:00:00
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
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abstract::Acoustic overstimulation causes apoptotic cell death in the cochlea. This death process is mediated, in part, by the mitochondrial signaling pathway involving Bcl-2 family proteins. Myeloid cell leukemia sequence 1 (Mcl-l) is an antiapoptotic member of the Bcl-2 family. Its involvement in noise-induced hair cell death...
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490280405
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journal_title:Journal of neuroscience research
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journal_title:Journal of neuroscience research
pub_type: 杂志文章
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