Revisiting influences on tumor development focusing on laboratory housing.

Spontaneous tumors are reported to occur in 45% to 71% of Sprague-Dawley rats, yet few studies have considered the effect of the sedentary condition of standard laboratory cages on tumorigenesis. Tumor profiles and tumor promoting hormone prolactin were compared in female Sprague-Dawley rats (108) that were allocated into 3 groups: those housed without outside activity (SED group), with twice-weekly 1-h sessions of physical activity in large box (PA group), and with regular voluntary running-wheel exercise (EX). Compared with the EX group, SED rats had more and larger tumors throughout most of their lifespan; tumor profiles of PA rats were similar to those of the SED group. A larger percentage of animals in the SED group had tumors (54%), compared with EX rats (38%). At 64 wk, tumors in SED animals included thyroid carcinoma, malignancy, mammary fibroadenoma, cystadenoma, and granuloma, whereas benign mammary gland cysts were most common in EX. Prolactin levels were highest in SED animals at 24 and 52 wk. In conclusion, increased tumor number, increased tumor size, type of spontaneous tumor, and increased prolactin in rats were associated with standard laboratory housing, which limited physical activity, and were not primarily due to aging.

Exercise-induced changes in cardiac gene expression and its relation to spatial maze performance.

Cognitive performance is sensitive to both neural and non-neural changes induced by physical activity and inactivity. This study investigated whether access to physical activity outside a standard laboratory animal cage affected cognitive performance as measured by navigation of a spatial maze. It also examined gene expression in heart tissue for genes associated with cardiovascular function given recent reports of cognitive impairment associated with hyperlipidemia. Furthermore, we measured expression of neural-regulatory genes typically expressed in brain, but also found in cardiac tissue. Male Sprague-Dawley rats (n = 72) were separated into three groups having different access to physical activity: none outside a standard cage, twice-weekly physical activity, and every other day exercise on a running wheel. Compared with a sedentary group, spatial maze performance was enhanced in animals that had access to physical activity, either twice-weekly in a large box or every other day on a running wheel. Both the cardiovascular and neural-related genes expressed in the heart were distinguished by access to physical activity. Several genes that are associated with heart rate, cholesterol biosynthesis, blood pressure, and cell adhesion regulation, including GJA1, FDFT1, EDN1, and CD36, differed in animals based on access to physical activity. Neural-related genes expressed in cardiac tissue associated with neurite outgrowth, neuroplasticity, and neurogenesis including RTN4, HOMER2, ACTB, NCDN, KIF5B, and HMGB2, were expressed differently among the three groups. Significant shifts in ten cardiovascular and neural-related gene expressions in cardiac tissue were associated with physical activity and may have influenced learning and performance on a spatial maze.

Access to exercise and its relation to cardiovascular health and gene expression in laboratory animals.

The interaction between genes and environment can influence cardiovascular disease (CVD). This 16 month study investigated if genes associated with cardiovascular (CV) regulation were expressed differently in animals having: 1) no access to physical activity or exercise (SED), 2) access to hour-long, twice weekly activity (PA), and 3) access every-other-day to a running wheel (EX). Out of 31,000 genes, a CV subset comprising 44 genes was investigated. Ten genes from this subset were expressed differently in EX compared with SED, and 34 genes were expressed differently in PA compared with SED (p<0.05). Total cholesterol (70+/-8 vs. 101+/-9 mg dl(-1)), triglycerides (104+/-8 vs. 127+/-4 mg dl(-1)), resting systolic blood pressure (130+/-3 vs. 141+/-3 mmHg), mean arterial pressure (110+/-2 vs. 120+/-2 mmHg) and heart rate (380+/-6 vs. 405+/-9 beats min(-1)) were lower in EX compared with SED (p<0.05), but intracellular adhesion molecule levels did not differ among groups. Mean gene expressions for Gja1, Fdft1, Edn1, Cd36, and Hmgb2 differed in animals according to access to physical activity. These genes play roles in heart rate, cholesterol biosynthesis, blood pressure, cell adhesion, and transcription and neurogenesis regulation, respectively. In conclusion, a total of 44 CV genes were expressed differently in SED compared to PA and EX; and SED showed more physiological evidence of CVD.