Circadian disruption induced by tumor development in a murine model of melanoma.

The circadian system induces oscillations in most physiological variables, with periods close to 24 hours. Dysfunctions in clock-controlled body functions, such as sleep disorders, as well as deregulation of clock gene expression or glucocorticoid levels have been observed in cancer patients. Moreover, these disorders have been associated with a poor prognosis or worse response to treatment. This work explored the circadian rhythms at behavioral and molecular levels in a murine melanoma model induced by subcutaneous inoculation of B16 tumoral cells. We observed that the presence of the tumors induced a decrease in the robustness of the locomotor activity rhythms and in the amount of nighttime activity, together with a delay in the acrophase and in the activity onset. Moreover, these differences were more marked when the tumor size was larger than in the initial stages of the tumorigenesis protocol. In addition, serum glucocorticoids, which exhibit strong clock-controlled rhythms, lost their circadian patterns. Similarly, the rhythmic expression of the clock genes Bmal1 and Cry1 in the hypothalamic Suprachiasmatic Nuclei (SCN) were also deregulated in mice carrying tumors. Altogether, these results suggest that tumor-secreted molecules could modulate the function of the central circadian pacemaker (SCN). This could account for the worsening of the peripheral biological rhythms such as locomotor activity or serum glucocorticoids. Since disruption of the circadian rhythms might accelerate tumorigenesis, monitoring circadian patterns in cancer patients could offer a new tool to get a better prognosis for this disease.

Social isolation impairs active avoidance performance and decreases neurogenesis in the dorsomedial telencephalon of rainbow trout.

Alterations in the social environment, such as isolating an individual that would normally live in a social group, can generate physiological responses that compromise an individual's capacity to learn. To investigate this, we tested whether social isolation impairs learning skills in the rainbow trout. We show that rainbow trout can achieve an active avoidance (AA) learning program with inter-individual variability. Moreover, c-Fos expression in dorsomedial telencephalon (Dm) correlates with the AA performance, indicating that this structure is involved in this cognitive task. Given that Dm participates in AA learning and this region is under plastic remodelling by addition of new-born neurons, we tested whether social isolation impinges on adult neurogenesis and, consequently, on the Dm cognitive outcome. Trout were reared for four weeks in control or isolated conditions. We found that social isolation diminished the percentage of adult-born neurons that are being incorporated into Dm network. Interestingly, the same isolation treatment also induced a severe deficit in the AA performance. Our results demonstrate a structure-to-function relationship between the Dm and the learning ability in an AA task, indicate that social isolation reduces the incorporation of adult-born neurons into Dm, and show that social isolation impairs the Dm-related cognitive function.