Long-term oral administration of a novel estrogen receptor beta agonist enhances memory and alleviates drug-induced vasodilation in young ovariectomized mice
| Autor: | Alicia M. Hanson, Edward A. Wetzel, Karyn M. Frick, Aaron W. Fleischer, Jayson C. Schalk, William A. Donaldson, Daniel S. Sem |
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| Rok vydání: | 2021 |
| Předmět: |
Agonist
medicine.medical_specialty Elevated plus maze Mouse medicine.drug_class Ovariectomy Diarylpropionitrile Hot flash Administration Oral Estrogen receptor Anxiety Article Open field Mice 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Object placement 0302 clinical medicine Endocrinology Internal medicine Nitriles medicine Animals Estrogen Receptor beta Humans ERβ Estrogen receptor beta Estradiol Depression Endocrine and Autonomic Systems business.industry Estrogen Receptor alpha Object recognition 030227 psychiatry Vasodilation Pharmaceutical Preparations chemistry Estrogen Ovariectomized rat Female Menopause business 030217 neurology & neurosurgery |
| Zdroj: | Hormones and behavior |
| ISSN: | 0018-506X |
| Popis: | Development of estrogen therapies targeting the β (ERβ) but not α (ERα) estrogen receptor is critically needed for the treatment of negative menopausal symptoms, as ERα activation increases health risks like cancer. Here, we determined the effects of long-term oral treatment with EGX358, a novel highly selective ERβ agonist, on memory, vasodilation, and affect in young ovariectomized mice. Mice were orally gavaged daily for 9 weeks with vehicle, 17β-estradiol (E2), the ERβ agonist diarylpropionitrile (DPN), or EGX358 at doses that enhance memory when delivered acutely. Tail skin temperature was recorded as a proxy for vasodilation following injection of vehicle or senktide, a tachykinin receptor 3 agonist used to model hot flashes. Anxiety-like behavior was assessed in the open field (OF) and elevated plus maze (EPM), and depression-like behavior was measured in the tail suspension (TST) and forced swim tests (FST). Finally, memory was assessed in object recognition (OR) and object placement (OP) tasks. E2, DPN, and EGX358 reduced senktide-mediated increases in tail skin temperature compared to vehicle. All three treatments also enhanced memory in the OR and OP tasks, whereas vehicle did not. Although E2 increased time spent in the center of the OF, no other treatment effects were observed in the OF, EPM, TST, or FST. These data suggest that long-term ERβ activation can reduce hot flash-like symptoms and enhance spatial and object recognition memories in ovariectomized mice. Thus, the highly selective ERβ agonist EGX358 may be a promising avenue for reducing menopause-related hot flashes and memory dysfunction. |
| Databáze: | OpenAIRE |
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