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Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model.

ABSTRACT: Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore, performed an evidence-based severity assessment of experimental procedures used in a pancreatic cancer model including surgical tumour induction and subsequent chemotherapeutic treatment via repeated intraperitoneal injections. Cancer cell injection into the pancreas was performed during a laparotomy under general anaesthesia. After a four-day recovery phase, mice received either drug treatment (galloflavin and metformin) or the respective vehicle substances via daily intraperitoneal injections. In addition to clinical scoring, an automated home-cage monitoring system was used to assess voluntary wheel running (VWR) behaviour as an indicator of impaired well-being. After surgery, slightly elevated clinical scores and minimal body weight reductions, but significantly decreased VWR behaviour were observed. During therapy, body weight declined in response to chemotherapy, but not after vehicle substance injection, while VWR activity was decreased in both cases. VWR behaviour differed between treatment groups and revealed altered nightly activity patterns. In summary, by monitoring VWR a high impact of repeated injections on the well-being of mice was revealed and substance effects on well-being were distinguishable. However, no differences in tumour growth between treatment groups were observed. This might be due to the severity of the procedures uncovered in this study, as exaggerated stress responses are potentially confounding factors in preclinical studies. Finally, VWR was a more sensitive indicator of impairment than clinical scoring in this model.

SUBMITTER: Weegh N

PROVIDER: S-EPMC8699632 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Endometriosis is a chronic gynecological disorder characterized by the growth of endometrial glands and stroma outside the endometrial cavity producing inflammation and pain. Previously we demonstrated that modulation of the hypothalamic pituitary adrenal (HPA) axis exacerbates the development and severity of this condition. A physically active lifestyle has been shown to confer health benefits in many chronic conditions by potentially acting as a stress buffer, thus we hypothesized that voluntary physical exercise can 'realign/reset' the HPA axis resulting in reduced endometriosis symptoms in an animal model.MethodsEndometriosis was induced in female Sprague Dawley rats by implanting uterine tissue next to the intestinal mesentery on day 0. Sham controls received sutures only. One group of endometriosis animals had access to a running wheel for 2 weeks prior to endometriosis induction until time of sacrifice at day 60. Sham and endometriosis controls received no exercise. All animals were examined for developed vesicles which were collected and measured. Uterine tissue was analyzed for cellular infiltration. Brain, liver, spleen, adrenal glands, leg muscles and fat were collected, along with peritoneal fluid and blood.ResultsEndometriosis animals developed vesicles in 86.96% of the implants with significantly increased mesenteric fat compared to sham (p<0.05). Exposure to exercise significantly decreased the size (p<0.01) and number (p<0.05) of vesicles that developed, as well as the mesenteric fat (p<0.01). Exercised animals had higher levels of lactoferrin in peritoneal fluid, and decreased serum fractalkine and leptin. Exercise significantly increased estrogen alpha receptor expression levels (p<0.01), while significantly decreasing estrogen receptor beta expression (p<0.01) and macrophage infiltration (p<0.05) in vesicles compared to non- exercised animals.ConclusionsOur results suggest that voluntary physical activity might protect against endometriosis and alleviate the associated inflammation via immune modulation of the HPA axis. This offers the potential for further exploration of exercise as a complementary therapy in endometriosis patients.

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Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model.

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