Allostatic tumor-burden induces depression-associated changes in hepatoma-bearing mice.
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.
Qi
Hong
H
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Ma
Jian
J
Liu
Yan-Mei
YM
Yang
Lan
L
Peng
Liang
L
Wang
Hao
H
Chen
Hong-Zhuan
HZ
D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D020904:Glia Maturation Factor / Q000235:genetics / Q000378:metabolism; D019417:Hindlimb Suspension / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000150:complications* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
D018687:Antidepressive Agents, Second-Generation; D019208:Brain-Derived Neurotrophic Factor; D020904:Glia Maturation Factor; D012333:RNA, Messenger; D005473:Fluoxetine; D013482:Superoxide Dismutase