Tumors induce gene-expression changes in the hippocampus, according to PNAS study.

Investigators at the University of Chicago have used an animal model to biologically link tumors and negative mood changes such as depression. The team determined that substances associated with depression are produced in increased quantities by tumors and are transmitted to the brain.

The research, documented in the article “Peripheral Tumors Induce Depressive-like Behaviors and Cytokine Production and Alter Hypothalamic-Pituitary-Andrenal Axis Regulation” that appears in the current issue of the Proceedings of the National Academy of Sciences, further showed that tumors affect changes in gene expression in the hippocampus, the portion of the brain that regulates emotion. Pathways that normally moderate the impact of depression-causing substances are disrupted when a tumor develops.

“Our research shows that two types of tumor-induced molecules, one secreted by the immune system and another by the stress axis, may be responsible,” says Leah Pyter, a postdoctoral fellow and lead author of the paper. “Both of these substances have been implicated in depression, but neither has been examined over time frames and magnitudes that are characteristic of chronic diseases such as cancer.”

The team conducted a series of tests on approximately 100 rats, some of whom had cancer, to determine their behavioral responses in tests of emotional state, that are commonly used in testing antidepressants. They found that the rats with tumors became less motivated to escape when submitted to a swimming test, a condition that is similar to depression in humans. The rats with tumors also were less eager to drink sugar water, a substance that usually attracts healthy rats.

Further tests revealed that the rats with tumors had increased levels of cytokines in their blood and in the hippocampus when compared with healthy rats. An increase in cytokines has been linked to depression. The investigators found that stress-hormone production was altered in rats with tumors as well. They also noticed that the rats with tumors had dampened production of the stress hormone corticosterone, which helps regulate the impact of cytokines. Reducing its production increases the impact of cytokines.

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