Dataset Information

Transcriptomic alterations across various cell types in the PFC

ABSTRACT: Major depressive disorder (MDD) is a prevalent mental illness that significantly impacts global health, with women showing twice the prevalence of men. This study employed the chronic social defeat stress (CSDS) model in female mice to investigate cellular and molecular changes in the prefrontal cortex (PFC) associated with depressive-like behaviors. Using single-nucleus RNA sequencing (snRNA-Seq), we examined transcriptomic alterations across various cell types in the PFC. Our results revealed that interneurons exhibited the most significant transcriptomic changes among all analyzed cell types. Notably, we identified a specific subtype of interneurons, the Sox6+ interneurons (Sox6+Int), which showed a markedly increased proportion in the CSDS group. This increase was associated with enhanced inflammatory and immune responses, as well as alterations in synaptic function and mitochondrial pathways. Furthermore, we observed significant changes in cell-cell communication patterns, particularly between Sox6+Int and oligodendrocyte precursor cells (OPCs). Weighted gene co-expression network analysis (WGCNA) identified several gene modules in Sox6+Int associated with specific depressive-like behaviors, implicating pathways related to inflammation, autophagy, and synaptic function. These findings provide novel insights into the cellular and molecular mechanisms underlying MDD in females, highlighting the potential role of Sox6+Int in stress-induced depression. Our study not only extends our understanding of the neurobiological basis of depression but also identifies potential therapeutic targets for sex-specific interventions in MDD treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE291951 | GEO | 2025/08/20

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidepressant drugs with novel mechanisms. Here, we found that norisoboldine (NOR) showed an antidepressant efficacy in the chronic social defeat stress (CSDS) depression model in the tail suspension, forced swimming, and sucrose consumption tests. We then utilized the drug-treated CSDS mice paradigm to segregate and gain differential protein cohorts of CSDS versus CON(CSDSCON), imipramine (IMI)-treated versus CSDS (IMICSDS), and NOR-treated versus CSDS (NORCSDS) from the prefrontal cortex. These protein expression alterations were first analyzed by ANOVA with p<0.05. The protein cluster 1, in which the pattern of protein levels similar to the mood pattern, showed enrichment in functions and localizations related to mitochondrion and synapses. Further GO analysis of the common proteins for NORCSDS-IMICSDS groups and NORCSDS-CSDSCON groups supported the findings from ANOVA analysis. We employed Protein-Protein interaction (PPI) analysis to examine the shared protein cohorts of NORCSDS-IMICSDS and NORCSDS-CSDSCON, revealing an enrichment of the proteins associated with the mitochondrial and synaptic functions. Further independent analysis using parallel reaction monitoring (PRM) revealed that several proteins related to mitochodrial function, including Cox7c, Mrp142, Naa30, Ighm, Ssu72, Mrps30, Apoh, Acbd5, and Cdv3, exhibited regulation in the NOR-treated group. Additionally, proteins associated with synaptic function, such as Dcx, Arid1b, Rnf112, Apoa4 and Fam3c, were also observed to undergo modulation in the NOR-treated groups. These findings suggest that the proteins involved in depression treatment exert differential effects the mitochondrial and synaptic regulation of the mice prefrontal proteome. In summary, the current proteomic research conducted on the prefrontal cortex has provided valuable insights into the specific and shared molecular mechanisms underlying pathophysiology and treatment to CSDS-induced depression, shedding light on the therapeutic effects of Norisoboldine.

Dataset Information

Transcriptomic alterations across various cell types in the PFC

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets