Depressive-like behaviours and decreased dendritic branching in the medial prefrontal cortex of mice with tumors: A novel validated model of cancer-induced depression

Nashed, Mina G.; Seidlitz, Eric; Frey, Benício N.; Singh, Gurmit

doi:10.1016/j.bbr.2015.07.040

Cited by 30 publications

(32 citation statements)

References 75 publications

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“…There was no main effect of treatment group on TST immobility (F (4,54) = 1.70, P = 0.163) or log 10 PM (F (4,54) = 1.32, P = 0.276). Here we independently replicated our previous finding that the TST is not sensitive in detecting passive coping behaviour in the CID model8.…”

Section: Resultssupporting

confidence: 88%

“…Tumour cell inoculations were performed as previously described8. Briefly, mice were inoculated with 15,000 4T1 cells in sterile phosphate buffered saline (PBS) subcutaneously above their right flank.…”

Section: Methodsmentioning

confidence: 99%

“…Behavioural tests were performed as previously described8. Anhedonia was evaluated using the sucrose preference test (SPT) and active versus passive coping behaviour was evaluated using the forced swim test (FST) and the tail suspension test (TST).…”

Section: Methodsmentioning

confidence: 99%

“…To investigate the underlying pathophysiology of CID and to explore novel targeted therapies, we have recently developed a validated mouse model of CID8. In this model, BALB/c mice that were subcutaneously inoculated with 4T1 mammary carcinoma cells exhibited similar behavioural and neurostructural deficits to those associated with a chronic stress-induced depressive-like state.…”

mentioning

confidence: 99%

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Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression

Nashed

Ungard

Young

et al. 2017

Sci Rep

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Despite the lack of robust evidence of effectiveness, current treatment options for cancer-induced depression (CID) are limited to those developed for non-cancer related depression. Here, anhedonia-like and coping behaviours were assessed in female BALB/c mice inoculated with 4T1 mammary carcinoma cells. The behavioural effects of orally administered sulfasalazine (SSZ), a system xc− inhibitor, were compared with fluoxetine (FLX). FLX and SSZ prevented the development of anhedonia-like behaviour on the sucrose preference test (SPT) and passive coping behaviour on the forced swim test (FST). The SSZ metabolites 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) exerted an effect on the SPT but not on the FST. Although 5-ASA is a known anti-inflammatory agent, neither treatment with SSZ nor 5-ASA/SP prevented tumour-induced increases in serum levels of interleukin-1β (IL-1β) and IL-6, which are indicated in depressive disorders. Thus, the observed antidepressant-like effect of SSZ may primarily be attributable to the intact form of the drug, which inhibits system xc−. This study represents the first attempt at targeting cancer cells as a therapeutic strategy for CID, rather than targeting downstream effects of tumour burden on the central nervous system. In doing so, we have also begun to characterize the molecular pathways of CID.

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Section: Resultssupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression

Nashed

Ungard

Young

et al. 2017

Sci Rep

Self Cite

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“…Despite inconsistent clinical evidence, modern antidepressants such as selective serotonin reuptake inhibitors (SSRIs) remain the primary therapy for cancer‐induced depression (CID; Li et al ; Ng et al ; Rodin et al ; Williams & Dale ). To investigate the pathophysiology of CID, we have recently developed and validated a mouse model of CID using subcutaneous inoculation of 4T1 mammary carcinoma cells in BALB/c mice (Nashed et al ). This model was validated against a positive control model for depressive‐like behavior induced by chronic administration of corticosterone (CORT).…”

mentioning

confidence: 99%

RNA‐sequencing profiles hippocampal gene expression in a validated model of cancer‐induced depression

Nashed

Linher‐Melville

Frey

et al. 2016

Genes Brain and Behavior

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To investigate the pathophysiology of cancer-induced depression (CID), we have recently developed a validated CID mouse model. Given that the efficacy of antidepressants in cancer patients is controversial, it remains unclear whether CID is a biologically distinct form of depression. We used RNA-sequencing (RNA-seq) to investigate differentially expressed genes (DEGs) in hippocampi of animals from our CID model relative a positive control model of depressive-like behavior induced with chronic corticosterone (CORT). To validate RNA-seq results, we performed quantitative real-time RT-PCR (qRT-PCR) on a subset of DEGs. Enrichment analysis using DAVID was performed on DEGs to identify enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and biological process gene ontologies (GO:BP). qRT-PCR results significantly predicted RNA-seq results. RNA-seq revealed that most DEGs identified in the CORT model overlapped with the CID model. Enrichment analyses identified KEGG pathways and GO:BP terms associated with ion homeostasis and neuronal communication for both the CORT and CID model. In addition, CID DEGs were enriched in pathways and terms relating to neuronal development, intracellular signaling, learning and memory. This study is the first to investigate CID at the mRNA level. We have shown that most hippocampal mRNA changes that are associated with a depressive-like state are also associated with cancer. Several other changes occur at the mRNA level in cancer, suggesting that the CID model may represent a biologically distinct form of a depressive-like state.

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The antioxidant and immunomodulatory compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole attenuates depression-like behavior and cognitive impairment developed in a mouse model of breast tumor

Casaril

Domingues

Bampi

et al. 2020

Brain, Behavior, and Immunity

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Depressive-like behaviours and decreased dendritic branching in the medial prefrontal cortex of mice with tumors: A novel validated model of cancer-induced depression

Cited by 30 publications

References 75 publications

Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression

Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression

RNA‐sequencing profiles hippocampal gene expression in a validated model of cancer‐induced depression

The antioxidant and immunomodulatory compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole attenuates depression-like behavior and cognitive impairment developed in a mouse model of breast tumor

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