Allostatic tumor-burden induces depression-associated changes in hepatoma-bearing mice (original) (raw)

Abstract

The high incidence of depression among cancer patients has created the need for deeper insights into its underlying pathophysiological mechanism. The aim of the current study is to demonstrate the presence of depressive states due to allostatic tumor-burden in the animal model, and if possible to elucidate the mechanism(s) by which the tumor might induce the depressive state. Stress-related behavioral responses and tumor weight were evaluated 6, 8, and 12 days after implantation of H22 hepatoma cells into the right flank of mice. Brain changes associated with depression were also observed 12 days after tumor implantation. The mice that were subjected to tumor-burden exhibited a significant depression-like state which manifested as behavioral changes including prolonged time spent immobile in the tail suspension test and reduced spontaneous motor activity with tumor progression. These behavior indices changed significantly 12 days after tumor implantation and were improved by the antidepressant fluoxetine. Correspondingly, the activity of superoxide dismutase (SOD) in the cerebrum and the expression of glia maturation factor beta (GMF-beta) and brain-derived neurotrophic factor (BDNF) in the hippocampus were significantly decreased in tumor-bearing mice, and these decreases were also reversed by fluoxetine. Taken together, these data indicate that tumor-burden might induce depressive-related behavior and brain changes, and suggest that antidepressants might not only palliate depression symptoms but also modify disease processes in the auxiliary treatment of cancer.

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Acknowledgments

This work was supported by the Shanghai Municipal Commission of Education Foundation (No 05BZ14) and by the National Natural Science Foundation of China (No 30672442).

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
    Hong Qi, Jian Ma, Yan-Mei Liu, Lan Yang, Liang Peng, Hao Wang & Hong-Zhuan Chen

Authors

  1. Hong Qi
  2. Jian Ma
  3. Yan-Mei Liu
  4. Lan Yang
  5. Liang Peng
  6. Hao Wang
  7. Hong-Zhuan Chen

Corresponding author

Correspondence toHong-Zhuan Chen.

Additional information

Hong Qi and Jian Ma contribute equally to the work.

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Qi, H., Ma, J., Liu, YM. et al. Allostatic tumor-burden induces depression-associated changes in hepatoma-bearing mice.J Neurooncol 94, 367–372 (2009). https://doi.org/10.1007/s11060-009-9887-3

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