Dataset Information

Anterior cingulate cortex mediates the comorbidity between colorectal cancer and depression-like behaviors

ABSTRACT: In this study, we established mice with orthotopic colorectal cancer (CRC mice) and observed depression-like behaviors in the CRC mice. Through whole-brain c-FOS mapping, functional connectivity analysis, gut-brain inverse mapping, and correlation analysis, combined with chemogenetic manipulation, we identified the anterior cingulate cortex (ACC) as a key hub in the depression-related brain network. we performed whole transcriptome sequencing of key neural nuclei to identify molecular changes associated with CRC-depression comorbidity. Furthermore, chemogenetic modulation of neuronal excitability not only alleviated depression-like behavior but also reduced CRC progression in these mice. Importantly, our findings suggest that targeting the ACC, in addition to conventional colorectal cancer therapies, could offer therapeutic and quality-of-life benefits for patients with both CRC and depression.

ORGANISM(S): Mus musculus

PROVIDER: GSE281840 | GEO | 2024/11/20

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Neuropathic pain is a chronic debilitating condition with a high comorbidity with depression. Clinical reports and animal studies have suggested that both the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) are critically implicated in regulating the affective symptoms of neuropathic pain. Neuropathic pain induces long-term structural, functional and biochemical changes in both regions, which are thought to be regulated by multiple waves of gene transcription. However, the similarity and differences in the transcriptomic profiles changed by neuropathic pain between these regions are largely unknown. Furthermore, women are more susceptible to pain and depression than men. The molecular mechanisms underlying this sexual dimorphism remain to be explored. Here, we performed RNA sequencing and analyzed the transcriptomic profiles of the mPFC and ACC of female and male mice at 2 weeks after spared nerve injury (SNI), an early time point when the mice began to show mild depressive symptoms. Our results show that the SNI-induced transcriptomic changes in female and male mice are largely distinct. Interestingly, the female mice exhibit more robust transcriptomic changes in the ACC than male, whereas the opposite pattern occurs in the mPFC. Cell type enrichment analyses reveal that the differentially expressed genes involve genes enriched in both neurons and various types of glia. We further performed Gene Set Enrichment Analysis (GSEA), which reveal significant de-enrichment of myelin sheath development in both female and male mPFC after SNI. In the female ACC, gene sets for synaptic organization and mitochondria function are enriched, and gene sets for extracellular matrix are de-enriched after SNI, while such signatures are absent in male ACC. Collectively, these findings reveal sexual dimorphism at the transcriptional level induced by neuropathic pain, and provide novel therapeutic targets for chronic pain and its associated affective disorders.

Dataset Information

Anterior cingulate cortex mediates the comorbidity between colorectal cancer and depression-like behaviors

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets