دورية أكاديمية
أعرض في EDS

Treatment with brain specific estrogen prodrug ameliorates cognitive effects of surgical menopause in mice.

التفاصيل البيبلوغرافية
العنوان: Treatment with brain specific estrogen prodrug ameliorates cognitive effects of surgical menopause in mice.
المؤلفون: Salinero AE; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Abi-Ghanem C; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Venkataganesh H; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Sura A; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Smith RM; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Thrasher CA; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Kelly RD; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Hatcher KM; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., NyBlom V; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA; Department of Psychology and Center for Neuroscience Research, State University of New York at Albany, 1400 Washington Ave, Biology 325, Albany, NY 12222, USA., Shamlian V; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Kyaw NR; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Belanger KM; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Gannon OJ; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Stephens SBZ; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA., Zuloaga DG; Department of Psychology and Center for Neuroscience Research, State University of New York at Albany, 1400 Washington Ave, Biology 325, Albany, NY 12222, USA., Zuloaga KL; Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY 12208, USA. Electronic address: zuloagk@amc.edu.
المصدر: Hormones and behavior [Horm Behav] 2024 Aug; Vol. 164, pp. 105594. Date of Electronic Publication: 2024 Jun 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 0217764 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-6867 (Electronic) Linking ISSN: 0018506X NLM ISO Abbreviation: Horm Behav Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, London, Academic Press.
مواضيع طبية MeSH: Ovariectomy* , Prodrugs*/pharmacology , Mice, Inbred C57BL* , Cognition*/drug effects , Brain*/drug effects , Brain*/metabolism , Menopause*/drug effects, Animals ; Female ; Mice ; Estrogens/pharmacology ; Estradiol/pharmacology
مستخلص: Menopause is an endocrine shift leading to increased vulnerability for cognitive impairment and dementia risk factors, in part due to loss of neuroprotective circulating estrogens. Systemic replacement of estrogen post-menopause has limitations, including risk for estrogen-sensitive cancers. A promising therapeutic approach therefore might be to deliver estrogen only to the brain. We examined whether we could enhance cognitive performance by delivering estrogen exclusively to the brain in ovariectomized mice (a surgical menopause model). We treated mice with the prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), which can be administered systemically but is converted to 17β-estradiol only in the brain. Young and middle-aged C57BL/6 J mice received ovariectomy and subcutaneous implant containing vehicle or DHED and underwent cognitive testing to assess memory after 1-3.5 months of treatment. Low and medium doses of DHED did not alter metabolic status in middle-aged mice. In both age groups, DHED treatment improved spatial memory in ovariectomized mice. Additional testing in middle-aged mice showed that DHED treatment improved working and recognition memory in ovariectomized mice. These results lay the foundation for future studies determining if this intervention is as efficacious in models of dementia with comorbid risk factors.
Competing Interests: Declaration of competing interest The authors have no conflicts to disclose.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
التعليقات: Update of: bioRxiv. 2023 Aug 13:2023.08.09.552687. doi: 10.1101/2023.08.09.552687. (PMID: 37609180)
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معلومات مُعتمدة: R01 NS110749 United States NS NINDS NIH HHS; U01 AG072464 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED); Dementia; Estrogen; Menopause; Ovariectomy; Spatial memory
المشرفين على المادة: 0 (Prodrugs)
0 (Estrogens)
4TI98Z838E (Estradiol)
تواريخ الأحداث: Date Created: 20240625 Date Completed: 20240818 Latest Revision: 20240820
رمز التحديث: 20240820
مُعرف محوري في PubMed: PMC11330726
DOI: 10.1016/j.yhbeh.2024.105594
PMID: 38917776
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-6867
DOI:10.1016/j.yhbeh.2024.105594