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CB1 agonism prolongs therapeutic window for hormone replacement in ovariectomized mice.
- Source :
-
Journal of Clinical Investigation . Jun2019, Vol. 129 Issue 6, p2333-2350. 18p. - Publication Year :
- 2019
-
Abstract
- Hormone therapy (HT) is reported to be deficient in improving learning and memory in older postmenopausal women according to recent clinical studies; however, the reason for failure is unknown. A "window of opportunity" for estrogen treatment is proposed to explain this deficiency. Here, we found that facilitation of memory extinction and long-term depression by 17β-estradiol (E2) was normal in mice 1 week after ovariectomy (OVXST), but it was impaired in mice 3 months after ovariectomy (OVXLT). High-throughput sequencing revealed a decrease of miR-221-5p, which promoted cannabinoid receptor 1 (CB1) ubiquitination by upregulation of Neurl1a/b in E2-treated OVXLT mice. Blood samples from postmenopausal women aged 56-65 indicated decreases of miR-221-5p and 2-arachidonoylglycerol compared with samples from perimenopausal women aged 46-55. Replenishing of miR-221-5p or treatment with a CB1 agonist rescued the impairment of fear extinction in E2-treated OVXLT mice. The present study demonstrates that an HT time window in mice can be prolonged by cotreatment with a CB1 agonist, implying a potential strategy for HT in long-term menopausal women. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CANNABINOID receptors
*MICE
*HORMONE therapy
*LONG-term memory
*FEAR
*SEXUAL desire disorders
*RNA metabolism
*THERAPEUTICS
*BIOCHEMISTRY
*RESEARCH
*HORMONES
*ESTRADIOL
*ANIMAL experimentation
*RESEARCH methodology
*CELL receptors
*RNA
*EVALUATION research
*MEDICAL cooperation
*PHENOMENOLOGY
*COMPARATIVE studies
*OVARIECTOMY
*POSTMENOPAUSE
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 129
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 137240844
- Full Text :
- https://doi.org/10.1172/JCI123689