A Method to Study the Impact of Chemically-induced Ovarian Failure on Exercise Capacity and Cardiac Adaptation in Mice

Abstract

The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet, the role of exercise, as a preventative measure for CVD risk in post-menopausal women has not been adequately studied. Accordingly, we investigated the impact of voluntary cage-wheel exercise and forced treadmill exercise on cardiac adaptation in menopausal mice. The most commonly used inducible model for mimicking menopause in women is the ovariectomized (OVX) rodent. However, the OVX model has a few dissimilarities from menopause in humans. In this study, we administered 4-vinylcyclohexene diepoxide (VCD) to female mice, which accelerates ovarian failure as an alternative menopause model to study the impact of exercise in menopausal mice. VCD selectively accelerates the loss of primary and primordial follicles resulting in an endocrine state that closely mimics the natural progression from pre-to peri-to post-menopause in humans. To determine the impact of exercise on exercise capacity and cardiac adaptation in VCD-treated female mice, two methods were used. First, we exposed a group of VCD-treated and untreated mice to a voluntary cage wheel. Second, we used forced treadmill exercise to determine exercise capacity in a separate group VCD-treated and untreated mice measured as a tolerance to exercise intensity and endurance.

APOE4 genotype exacerbates the impact of menopause on cognition and synaptic plasticity in APOE‐TR mice

“…The VCD model system is a well‐established method for inducing a “menopause” like state in rodents 23 and is well‐tolerated leading to a targeted degradation of ovarian follicles 24 . Eight months was selected as it is roughly midlife for the animals (when human menopause occurs) and before natural ovarian failure is known to occur in C57BL/6 mice 25,26 . Following completion of the final behavioral test, 12‐month aged animals were sedated with isoflurane (1.5%) in a mixture of nitrous oxide (70%), and oxygen (30%) and transcardially perfused with an ice‐cold PBS‐containing protease (SIGMAFAST Protease inhibitor, Sigma‐Aldrich, Devon, UK) and phosphatase (1 mM sodium pyrophosphate and 50 mM sodium fluoride, Sigma‐Aldrich, Devon, UK) inhibitors.…”

The VCD Mouse Model of Menopause and Perimenopause for the Study of Sex Differences in Cardiovascular Disease and the Metabolic Syndrome

“…Therefore, the VCD model has also been used to assess the ability of menopause to influence physical activity and the response to exercise in female mice (3,6,16). In young female mice, wheel-running distance was similar between control animals and VCD-treated animals with or without 17-␤ estradiol treatment (6).…”

Manipulation of Neurotransmitter Levels Has Differential Effects on Formalin-Evoked Nociceptive Behavior in Male and Female Mice

“…Noncycling mice were divided into 2 categories on the basis of vaginal lavage samples: anestrus, described by a mixture of unidentifiable cell types, and prolonged diestrus, characterized by a large amounts of leukocytes, typical of periods of low estrogen and progesterone. 1,13,29 Cast and sham surgery male mice were not tested until a minimum of 14 days after surgery to ensure that all circulating testosterone had diminished. 8,36,65 Experiment 6: Pharmacological Antagonism of N 2 -AcPLZ-Mediated Antinociception in Male Mice Different pharmacological agents were used to determine if the analgesic effects of N 2 -AcPLZ in male mice could be reversed.…”