title: Hippocampal dysfunctions in tumor-bearing mice.
abstract: Individuals with cancer are particularly susceptible to depression and cognitive impairment. However, the precise mechanisms underlying cancer-induced hippocampal dysfunction are poorly understood. We investigated the effects of a peripheral tumor on emotional behavior, hippocampus-dependent memory and associated molecular and cellular features using an experimental animal model. Behavioral alterations were examined; stress-related parameters measured; hippocampal neurogenesis evaluated; and the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2) assayed, 2 weeks after inoculation of adult BALB/c mice with cells of a colon carcinoma cell line (CT26). As the tumors developed, CT26-inoculated mice showed significant increases in the depression-like behavior (measured using the tail suspension test) and memory impairment (in terms of object recognition) compared with vehicle-inoculated controls. The presence of a peripheral tumor significantly elevated the hippocampal levels of mRNAs encoding interleukin-6 (IL-6) and tumor necrosis factor-α, as well as plasma IL-6 and corticosterone levels. Additionally, the adrenal glands became enlarged, and the numbers of Ki-67-positive proliferating hippocampal cells and doublecortin-positive immature progenitor neurons, as well as the constitutive levels of mRNAs encoding BDNF and COX-2 were significantly reduced. Therefore, a peripheral tumor alone may be sufficient to induce hippocampal dysfunction, possibly by reducing the rate of neurogenesis and the levels of BDNF and COX-2 in that tissue and also by increasing stress-related parameters and the circulating levels of pro-inflammatory cytokines.
authors: Miyoung
authors: M
authors: Yang
authors: Juhwan
authors: J
authors: Kim
authors: Joong-Sun
authors: JS
authors: Kim
authors: Sung-Ho
authors: SH
authors: Kim
authors: Jong-Choon
authors: JC
authors: Kim
authors: Man-Jong
authors: MJ
authors: Kang
authors: Uhee
authors: U
authors: Jung
authors: Taekyun
authors: T
authors: Shin
authors: Hongbing
authors: H
authors: Wang
authors: Changjong
authors: C
authors: Moon
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D045744:Cell Line, Tumor; D003345:Corticosterone / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003863:Depression / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology; D013312:Stress, Physiological
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D003345:Corticosterone