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Estradiol treatment improves biological rhythms in a preclinical rat model of menopause.

ABSTRACT: The perimenopausal transition at middle age is often associated with hot flashes and sleep disruptions, metabolic changes, and other symptoms. Whereas the mechanisms for these processes are incompletely understood, both aging (AG) and a loss of ovarian estrogens play contributing roles. Furthermore, the timing of when estradiol (E) treatment should commence and for how long are key clinical questions in the management of symptoms. Using a rat model of surgical menopause, we determined the effects of regimens of E treatment with differing time at onset and duration of treatment on diurnal rhythms of activity and core temperature and on food intake and body weight. Reproductively mature (MAT, ?4 months) or AG (?11 months) female rats were ovariectomized, implanted intraperitoneally with a telemetry device, and given either a vehicle (V) or E subcutaneous capsule implantation. Rats were remotely recorded for 10 days per month for 3 (MAT) or 6 (AG) months. To ascertain whether delayed onset of treatment affected rhythms, a subset of AG-V rats had their capsules switched to E at the end of 3 months. Another set of AG-E rats had their capsules removed at 3 months to determine whether beneficial effects of E would persist. Overall, activity and temperature mesor, robustness, and amplitude declined with AG. Compared to V treatment, E-treated rats showed (1) better maintenance of body weight and food intake; (2) higher, more consolidated activity and temperature rhythms; and (3) higher activity and temperature robustness and amplitude. In the AG arm of the study, switching treatment from V to E or E to V quickly reversed these patterns. Thus, the presence of E was the dominant factor in determining stability and amplitude of locomotor activity and temperature rhythms. As a whole, the results show benefits of E treatment, even with a delay, on biological rhythms and physiological functions.

SUBMITTER: Yin W

PROVIDER: S-EPMC6858967 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Estradiol treatment improves biological rhythms in a preclinical rat model of menopause.

Yin Weiling W Borniger Jeremy C JC Wang Xutong X Maguire Sean M SM Munselle Mercedes L ML Bezner Kelsey S KS Tesfamariam Haben M HM Garcia Alexandra N AN Hofmann Hans A HA Nelson Randy J RJ Gore Andrea C AC

Neurobiology of aging 20190909

The perimenopausal transition at middle age is often associated with hot flashes and sleep disruptions, metabolic changes, and other symptoms. Whereas the mechanisms for these processes are incompletely understood, both aging (AG) and a loss of ovarian estrogens play contributing roles. Furthermore, the timing of when estradiol (E) treatment should commence and for how long are key clinical questions in the management of symptoms. Using a rat model of surgical menopause, we determined the effect ...[more]

PMID: 31585360

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Project description:BackgroundMyocardial dysfunction is a major cause of poor outcomes in the post-cardiac arrest period. Omecamtiv mecarbil (OM) is a selective small molecule activator of cardiac myosin that prolongs myocardial systole and increases stroke volume without apparent effects on myocardial oxygen demand. OM administration is safe and improves cardiac function in patients with acute heart failure. Whether OM improves post-resuscitation myocardial dysfunction remains unclear. This study investigated the effect of OM treatment on post-resuscitation myocardial dysfunction and outcomes.Methods and resultsAdult male rats were resuscitated after 9.5 min of asphyxia-induced cardiac arrest. OM and normal saline was continuously intravenously infused after return of spontaneous circulation (ROSC) at 0.25 mg/kg/h for 4 h in the experimental group and control group, respectively (n = 20 in each group). Hemodynamic parameters were measured hourly and monitored for 4 h after cardiac arrest. Recovery of neurological function was evaluated by neurological functioning scores (0-12; favorable: 11-12) for rats 72 h after cardiac arrest. OM treatment prolonged left ventricular ejection time and improved post-resuscitation cardiac output. Post-resuscitation heart rate and left ventricular systolic function (dp/dt40) were not different between groups. Kaplan-Meier analysis showed non-statistically higher 72-h survival in the OM group (72.2% [13/18] and 58.8% [10/17], p = 0.386). The OM group had a higher chance of having favorable neurological outcomes in surviving rats 72 h after cardiac arrest (84.6% [11/13] vs. 40% [4/10], p = 0.026). The percentage of damaged neurons was lower in the OM group in a histology study at 72 h after cardiac arrest (55.5±2.3% vs. 76.2±10.2%, p = 0.004).ConclusionsOM treatment improved post-resuscitation myocardial dysfunction and neurological outcome in an animal model. These findings support further pre-clinical studies to improve outcomes in post-cardiac arrest care.

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Estradiol treatment improves biological rhythms in a preclinical rat model of menopause.

Publications

Estradiol treatment improves biological rhythms in a preclinical rat model of menopause.

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