Dataset Information

Circuit-wide Proteomics Profiling Reveals Brain Region-specific Protein Signatures in the WKY Rats with Endogenous Depression

ABSTRACT: Major depressive disorder (MDD) is considered as a neural circuit-based polygene syndrome that is mainly triggered by genetic susceptibility and stress factors. The present study employed the Wistar Kyoto (WKY) rat as an animal model with endogenous depression to further investigate the molecular basis of its genetic susceptibility to depression by performing quantitative protemoics analyses of the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and hippocampus (Hip), respectively.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Jiangfeng Liao

LAB HEAD: Xiaochun Chen

PROVIDER: PXD029079 | Pride | 2022-10-13

REPOSITORIES: pride

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Circuit-wide proteomics profiling reveals brain region-specific protein signatures in the male WKY rats with endogenous depression.

Liao Jiangfeng J Mi Xue X Zeng Guirong G Wei Yuanxiang Y Dai Xiaoman X Ye Qinyong Q Chen Xiaochun X Zhang Jing J

Journal of affective disorders 20220923

<h4>Background</h4>Although the Wistar Kyoto (WKY) rat has been consistently recognized as an animal model with endogenous depression, the exact molecular mechanisms underlying its genetic susceptibility to depression remain undetermined.<h4>Methods</h4>Compared with the Wistar rats, the depression-like behaviors of the male WKY ones were evaluated by both the sucrose preference test and forced swimming test. Golgi staining analysis was conducted to access the dendritic morphology. TMT-labelled ...[more]

PMID: 36162674

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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.

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	Hip_Z8535TQ_1.raw	Raw
	Hip_Z8535TQ_2.raw	Raw
	Hip_Z8535TQ_3.raw	Raw
	Hip_Z8535TQ_4.raw	Raw
	Hip_Z8535TQ_5.raw	Raw