We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced serum leptin concentrations, and enhanced sensitivity to exogenous ghrelin. We tested whether these phenotypes were driven by inflammation using neutralizing monoclonal antibodies against IL-6; despite the reduction in IL-6 signaling, metabolic and sleep abnormalities persisted. We next investigated neural populations coupling metabolism and sleep, and observed altered activity within lateral-hypothalamic hypocretin/orexin (HO) neurons. We used a dual HO-receptor antagonist to test whether increased HO signaling was causing metabolic abnormalities. This approach rescued metabolic abnormalities and enhanced sleep quality in tumor-bearing mice. Peripheral sympathetic denervation prevented tumor-induced increases in serum glucose. Our results link metabolic and sleep abnormalities via the HO system, and provide evidence that central neuromodulators contribute to tumor-induced changes in metabolism.

Light has substantial influences on the physiology and behavior of most laboratory animals. As such, lighting conditions within animal rooms are potentially significant and often underappreciated variables within experiments. Disruption of the light/dark cycle, primarily by exposing animals to light at night (LAN), disturbs biological rhythms and has widespread physiological consequences because of mechanisms such as melatonin suppression, sympathetic stimulation, and altered circadian clock gene expression. Thus, attention to the lighting environment of laboratory animals and maintaining consistency of a light/dark cycle is imperative for study reproducibility. Light intensity, as well as wavelength, photoperiod, and timing, are all important variables. Although modern rodent facilities are designed to facilitate appropriate light cycling, there are simple ways to modify rooms to prevent extraneous light exposure during the dark period. Attention to lighting conditions of laboratory animals by both researchers and research care staff ensures best practices for maintaining animal welfare, as well as reproducibility of research results. (PsycINFO Database Record

Understanding why breast cancer survivors are at an increased risk for cognitive and affective disorders is essential for developing targeted treatment plans and improving quality of life. Microglia priming results in chronic neuroinflammation and can contribute to neuronal degeneration and dysfunction, thereby offering a potential mechanism for altered brain function that persists after tumor removal. This study examined whether mammary tumors alter microglia and augment the inflammatory profile and behavior of mice. To test this, non-metastatic mammary tumor cells (67NR) were injected orthotopically into the mammary glands of BALB/c mice, allowed to grow for 16 days, and then the tumors were removed via mastectomy. Following a 14day surgical recovery, the mice were challenged with lipopolysaccharide (LPS), and then central and peripheral inflammation, anxiety, and depressive-like behavior were evaluated. Here we show that major central and peripheral inflammatory markers were not altered by tumor growth nor mastectomy surgery alone. However, hippocampal mRNA expression of major proinflammatory cytokines IL-1β and TNFα was increased in tumor removal animals, persisting past surgical recovery. Nonetheless, the immune and behavioral responses following LPS administration were comparable among groups. In sum, these data demonstrate that the combination of tumor and mastectomy promotes neuroinflammation; however, immune challenge did not elucidate this inflammation as maladaptive for the host.

level and improve surgical outcomes. Recently, some institutions have approved the use of Press'n Seal cling film (CF; Glad Products, Oakland, CA) as a practical, cost-effective alternative to sterile drapes for rodent surgeries. The purpose of this study was to evaluate the sterility of CF by using ATP and replicate organism detection and counting (RODAC) plates. We tested 10 boxes of CF at days 0, 14, and 28 after opening the box and compared the results with traditional packaged sterile drapes. Our data indicated that CF ATP bioluminescence remained at or below 10 relative light units for 28 d after opening the box. In addition, RODAC plates had no growth for 70% of CF boxes at day 0, 100% at day 14, and 90% at day 28. The mean growth for the positive plates was 0.024 cfu/cm2 sampled after contacting locations on the front and back of the CF. The results of this study support the use of CF as an acceptable alternative to traditional sterile drapes during rodent aseptic surgery.