Zhizi Chi (Gardeniae Fructus and Semen Sojae Praeparatum) Decoction attenuates anxious depression via modulation of intestinal bacteria and reward nerve center
Ontology highlight
ABSTRACT:
ORGANISM(S): Gardenia Jasminoides
SUBMITTER: 
Ke Ma
PROVIDER: PXD040673 | iProX | Tue Mar 07 00:00:00 GMT 2023
REPOSITORIES: iProX
Similar Datasets
Project description:Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. mRNA profiles of sex-specific in stress response were generated in the Nucleus Accumbens for 3 female control mice, 3 male control mice, 3 stressed female mice, 3 stressed male mice. Cre-mediated Dnmt3a knock-out was performed on stressed mice, with 3 males and 3 females expressing control GFP and 3 males and 3 females expressing CRE/GFP.
2016-08-04 | E-GEOD-85136 | biostudies-arrayexpress
Project description:Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability.
2016-08-04 | GSE85136 | GEO
Project description:We demonstrated that the offspring of depressed fathers display reduced resilience to stress and enhanced susceptibility to depression. To explain the observed behavioural phenotypes of depression in offspring produced by depressed fathers, molecular profiling was performed in key brain regions.We examined the hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice by RNA sequencing.
2020-06-28 | GSE133494 | GEO
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB and LAB mice. Analysis was performed from six animals per line (HAB and LAB, respectively) pooled per brain region in ten technical replicates, thereof five with a dye-swapped design giving a total of 70 array slides analyzed. The LAB mouse line is referred to as reference.
2011-08-29 | E-GEOD-28999 | biostudies-arrayexpress
Project description:Here we show that ?-catenin mediates pro-resilient and anxiolytic effects in mice in the nucleus accumbens (NAc), a key brain reward region, an effect that is mediated by ?-catenin signaling in D2-type medium spiny neurons (MSNs) specifically. Conversely, blocking ?-catenin function in NAc promotes susceptibility to chronic stress, and we show evidence of robust suppression of ?-catenin transcriptional activity in the NAc both of depressed humans examined postmortem as well as of mice that display a susceptible phenotype after chronic stress, with a converse upregulation in mice that are stress resilient. Using ChIP-seq, we demonstrate a global, genome-wide enrichment of ?-catenin in the NAc of resilient mice, and specifically identify Dicer1—important in small RNA (e.g., microRNA [miRNA]) biogenesis—as a critical ?-catenin target gene involved in mediating a resilient phenotype. Small RNA-seq after excising ?-catenin from the NAc in the context of chronic stress reveals dynamic ?-catenin-dependent miRNA regulation associated with resilience. Control: 2 samples, Resilient: 2 samples, Susceptible: 2 samples; DNA input: 1 sample.
2014-11-13 | E-GEOD-61294 | biostudies-arrayexpress
Project description:Here we show that ?-catenin mediates pro-resilient and anxiolytic effects in mice in the nucleus accumbens (NAc), a key brain reward region, an effect that is mediated by ?-catenin signaling in D2-type medium spiny neurons (MSNs) specifically. Conversely, blocking ?-catenin function in NAc promotes susceptibility to chronic stress, and we show evidence of robust suppression of ?-catenin transcriptional activity in the NAc both of depressed humans examined postmortem as well as of mice that display a susceptible phenotype after chronic stress, with a converse upregulation in mice that are stress resilient. Using ChIP-seq, we demonstrate a global, genome-wide enrichment of ?-catenin in the NAc of resilient mice, and specifically identify Dicer1—important in small RNA (e.g., microRNA [miRNA]) biogenesis—as a critical ?-catenin target gene involved in mediating a resilient phenotype. Small RNA-seq after excising ?-catenin from the NAc in the context of chronic stress reveals dynamic ?-catenin-dependent miRNA regulation associated with resilience. GFP_Control: 12 samples, GFP_Resilient: 12 samples, GFP_Susceptible: 4 samples; CRE_Control: 12 samples, CRE_Susceptible: 8 samples.
2014-11-13 | E-GEOD-61295 | biostudies-arrayexpress
Project description:Background Chronic anxiety imposes a major global health burden, yet existing treatments remain inadequate, with limited efficacy or significant side effects. Mitochondrial abnormalities have emerged as key contributors to anxiety-related phenotypes, suggesting that targeting mitochondrial function may offer a novel therapeutic avenue. Urolithin A (UA), a gut microbiota-derived metabolite known to enhance mitochondrial function, has shown neuroprotective effects in preclinical models of aging and neurodegeneration. However, its potential in modulating anxiety and underlying neuronal mechanisms remains unexplored. Methods We examined the effects of UA in two rodent models of heightened anxiety: a natural variation model and a genetically selected high stress-reactivity line. Animals received chronic UA supplementation, and anxiety-like behaviors were assessed across multiple paradigms. Single-nucleus RNA sequencing was performed to identify molecular alterations in nucleus accumbens (NAc) medium spiny neurons (MSNs), incorporating MitoPathway analyses to examine mitochondrion-related transcriptomic signatures. Electrophysiological, immunohistochemical, and morphological analyses were conducted to assess mitochondrial pathways and synaptic function. Results UA selectively reduced anxiety-like behaviors in high-anxiety animals, both males and females, leaving non-anxious controls unaffected. Transcriptomic analyses revealed widespread mitochondrial and synaptic dysregulation in high-anxiety MSNs, with impaired mitophagy emerging as a core feature. UA treatment restored these transcriptomic signatures, normalizing mitophagy-related pathways across all MSN subtypes tightly linked to restored synaptic pathways. These changes translated into structural and functional rescue of MSN dendritic architecture, spine density, and excitatory synaptic transmission. Conclusions These findings identify mitophagy deficits in NAc MSNs as a hallmark of heightened anxiety and highlight UA as a promising mechanism-based intervention.
2025-09-01 | GSE297773 | GEO
Project description:Here we show that β-catenin mediates pro-resilient and anxiolytic effects in mice in the nucleus accumbens (NAc), a key brain reward region, an effect that is mediated by β-catenin signaling in D2-type medium spiny neurons (MSNs) specifically. Conversely, blocking β-catenin function in NAc promotes susceptibility to chronic stress, and we show evidence of robust suppression of β-catenin transcriptional activity in the NAc both of depressed humans examined postmortem as well as of mice that display a susceptible phenotype after chronic stress, with a converse upregulation in mice that are stress resilient. Using ChIP-seq, we demonstrate a global, genome-wide enrichment of β-catenin in the NAc of resilient mice, and specifically identify Dicer1—important in small RNA (e.g., microRNA [miRNA]) biogenesis—as a critical β-catenin target gene involved in mediating a resilient phenotype. Small RNA-seq after excising β-catenin from the NAc in the context of chronic stress reveals dynamic β-catenin-dependent miRNA regulation associated with resilience.
2014-11-13 | GSE61295 | GEO
Project description:Here we show that β-catenin mediates pro-resilient and anxiolytic effects in mice in the nucleus accumbens (NAc), a key brain reward region, an effect that is mediated by β-catenin signaling in D2-type medium spiny neurons (MSNs) specifically. Conversely, blocking β-catenin function in NAc promotes susceptibility to chronic stress, and we show evidence of robust suppression of β-catenin transcriptional activity in the NAc both of depressed humans examined postmortem as well as of mice that display a susceptible phenotype after chronic stress, with a converse upregulation in mice that are stress resilient. Using ChIP-seq, we demonstrate a global, genome-wide enrichment of β-catenin in the NAc of resilient mice, and specifically identify Dicer1—important in small RNA (e.g., microRNA [miRNA]) biogenesis—as a critical β-catenin target gene involved in mediating a resilient phenotype. Small RNA-seq after excising β-catenin from the NAc in the context of chronic stress reveals dynamic β-catenin-dependent miRNA regulation associated with resilience.
2014-11-13 | GSE61294 | GEO
Project description:In this study monoclonal cell lines carrying mutations in IFITM3 gene were obtained based on WI-38 VA13 cells. To research the involvement of the IFITM3 gene in cellular response to Influenza A virus infection, original WI-38 VA13 cells and the clones with depressed IFITM3 gene activity (F3, F5, Е12) were infected with influenza A/Puerto Rico/8/1934 (H1N1) virus. RNA-seq analysis of infected cell lines after 24 h was performed on an Illumina NextSeq 500 platform. The same mock-infected cells were used as controls (0 hpi). PolyA RNA-enriched fraction was used for constructing of cDNA libraries. Differential expressed genes were identified using R package DESeq2.
2023-12-16 | E-MTAB-13582 | biostudies-arrayexpress