| Sex-dimorphic effects of dehydroepiandrosterone in diabetic neuropathy. | |
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MedLine Citation:
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PMID: 21945035 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Our recent observations have demonstrated that gonadectomy in female, but not in male diabetic animals, exert protection in the peripheral nervous system and that these effects were associated with an increase in the levels of dehydroepiandrosterone (DHEA) in the female sciatic nerve [Pesaresi M, Giatti S, Cavaletti G, Abbiati F, Calabrese D, Bianchi R, Caruso D, Garcia-Segura LM, Melcangi RC (2011) Exp Neurol 228:215-221]. That is interesting because the neuroprotective effects of this neuroactive steroid have so far only been analyzed in male diabetic animals. Using the experimental model of streptozotocin-induced diabetic neuropathy, we have here compared the effect of DHEA treatment in male and in female animals. Data obtained indicate that DHEA treatment is able to counteract the decrease in nerve conduction velocity (NCV) induced by diabetes in both sexes. However, it was only in females that this neuroactive steroid was able to reestablish NCV to control levels. In addition, it was only in females that DHEA exerted neuroprotective actions on functional (i.e., thermal sensitivity) or molecular parameters, such as gene expression of myelin proteins. Sex-depending neuroprotective effects of DHEA were also confirmed by the finding that it was only in females that this neuroactive steroid fully restored the intra-epidermal nerve fiber density, which was decreased by diabetes. Interestingly, the metabolic fate of DHEA is also different in males and females. Thus, analysis of the neuroactive steroid levels after the treatment with DHEA indicates that in the sciatic nerve of male diabetic animals 17α-estradiol levels decrease in association with an increase of its isomer 17β-estradiol and with a decrease in the levels of α-androstane-3α, 17β-diol. These changes were not observed in the sciatic nerve of females. Altogether, these results suggest that DHEA could be considered as a candidate for a sex-specific therapy based on neuroactive steroids. |
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Authors:
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M Pesaresi; S Giatti; G Cavaletti; F Abbiati; D Calabrese; R Lombardi; R Bianchi; G Lauria; D Caruso; L M Garcia-Segura; R C Melcangi |
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Publication Detail:
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Type: - Date: 2011-9-16 |
Journal Detail:
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Title: Neuroscience Volume: - ISSN: 1873-7544 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ltd. |
Affiliation:
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Department of Endocrinology, Pathophysiology and Applied Biology - Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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