Iron-induced neuronal damage in a rat model of post-traumatic stress disorder

Zhao, Ming; Yu, Zhaojie; Zhang, Yang; Huang, Xueling; Hou, Jingming; Zhao, Yangang; Luo, Wei; Chen, Lin; Ou, Lan; Li, Haitao; Zhang, Jiqiang

doi:10.1016/j.neuroscience.2016.05.025

Cited by 11 publications

(5 citation statements)

References 52 publications

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“…In a clinical study, PTSD patients exhibited downregulation of certain genes related to the oxidative phosphorylation pathway in the dorsolateral prefrontal cortex, including Atp5e, Cox8a, NADH: ubiquinone oxidoreductase subunit B5 (Ndufb5), and NADH: ubiquinone oxidoreductase core subunit S2 (Ndufs2) [61]. Our results align with prior research that reported mitochondrial dysfunction in the prefrontal cortex of rats with PTSD through RNA sequencing [62,63]. More than 90% of the cellular energy generation takes place within the mitochondria through a process known as oxidative phosphorylation, and it has also been found that oxidative phosphorylation is a biochemical process that occurs in the inner mitochondrial membrane; it fuels neuronal physiological functions by producing ATP energy stores [64].…”

Section: Oxidative Phosphorylation and The Regulation Of Cbd In Ptsdsupporting

confidence: 87%

Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts

Xie,

Qin,

et al. 2024

Genes

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Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and the mechanisms of CBD against this disease, we conducted single-nucleus RNA sequencing (snRNA-seq) in the hippocampus of PTSD-modeled mice and CBD-treated cohorts. We constructed a mouse model by adding electric foot shocks following exposure to single prolonged stress (SPS+S) and tested the freezing time, anxiety-like behavior, and cognitive behavior. CBD was administrated before every behavioral test. The PTSD-modeled mice displayed behaviors resembling those of PTSD in all behavioral tests, and CBD treatment alleviated all of these PTSD-like behaviors (n = 8/group). Three mice with representative behavioral phenotypes were selected from each group for snRNA-seq 15 days after the SPS+S. We primarily focused on the excitatory neurons (ExNs) and inhibitory neurons (InNs), which accounted for 68.4% of the total cell annotations. A total of 88 differentially upregulated genes and 305 differentially downregulated genes were found in the PTSD mice, which were found to exhibit significant alterations in pathways and biological processes associated with fear response, synaptic communication, protein synthesis, oxidative phosphorylation, and oxidative stress response. A total of 63 overlapping genes in InNs were identified as key genes for CBD in the treatment of PTSD. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the anti-PTSD effect of CBD was related to the regulation of protein synthesis, oxidative phosphorylation, oxidative stress response, and fear response. Furthermore, gene set enrichment analysis (GSEA) revealed that CBD also enhanced retrograde endocannabinoid signaling in ExNs, which was found to be suppressed in the PTSD group. Our research may provide a potential explanation for the pathogenesis of PTSD and facilitate the discovery of novel therapeutic targets for drug development. Moreover, it may shed light on the therapeutic mechanisms of CBD.

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Section: Oxidative Phosphorylation and The Regulation Of Cbd In Ptsdsupporting

confidence: 87%

Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts

Xie,

Qin,

et al. 2024

Genes

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“…-7 M in humans [30] and 2.7-5.4x10 -8 M in rats [31]. The requirement for dexamethasone for adequate osteogenesis and adipogenesis in in vitro experiments has been reported previously [32,33].…”

Section: Discussionmentioning

confidence: 74%

Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats

Huang

Cheng

Cao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glucocorticoid (GC)-related osteonecrosis of the femoral head (ONFH) is a common complication following administration of steroids to treat many diseases. Our previous study demonstrated that icariin (ICA) might have a beneficial effect on the bone marrow mesenchymal stem cells (BMSCs) of patients with steroid-associated osteonecrosis. In this study, we investigated the underlying mechanisms of ICA associated with the potential enhancement of osteogenesis and anti-adipogenesis in GC-related ONFH. Methods: In vitro cell proliferation was evaluated by CCK-8 assay. Alizarin red S and alkaline phosphatase (ALP) activity were used to measure osteogenic differentiation, while adipogenic differentiation was revealed by oil red O staining and TG content assay. The expression level of osteogenesis-associated genes and PPARγ was evaluated by RT-qPCR, western blotting and immunofluorescence. A total of 30 female SD rats were randomly separated into three groups: a control group, a methylprednisolone (MPS) group and a MPS + ICA group. Serum ALP and TG (triglyceride), micro-CT scanning, histological and immunohistochemical analyses were performed in the animal model. Results: In the in vitro study, ICA promoted proliferation, improved osteogenic differentiation and suppressed adipogenic differentiation of BMSCs treated with MPS. The group treated with MPS and 10^-6 M ICA expressed higher levels of Runx2, ALP, bone morphogenetic protein (BMP) 2, and OC and lower expression of PPARγ than the MPS group. In the in vivo study, ICA prevented bone loss in a rat model of GC-related ONFH as shown by micro-CT scanning, histological and immunohistochemical analyses. Conclusions: ICA is an effective compound for promoting bone repair and preventing or delaying the progression of GC-associated ONFH in rats. This effect can be explained by its ability to improve the balance between adipogenesis and osteogenesis, indicating that ICA is an effective candidate for management of GC-associated ONFH.

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“…The main biochemical mechanism of ferroptosis is the catalysis of polyunsaturated fatty acids (PUFAs) that causes lipid peroxidation under the action of catalytic Fe (II) ( 41 ). Animal models of PTSD suggest increased iron in cognition-related brain regions, resulting in neuronal injury ( 42 ). Hence, high catalytic Fe (II) abundance indicates high levels of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Blood transcriptome analysis: Ferroptosis and potential inflammatory pathways in post-traumatic stress disorder

et al. 2022

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BackgroundTranscriptome-wide analysis of peripheral blood in post-traumatic stress disorder (PTSD) indicates widespread changes in immune-related pathways and function. Ferroptosis, an iron-dependent regulated cell death, is closely related to oxidative stress. However, little is known as to whether ferroptosis plays a role in PTSD.MethodsWe conducted a comprehensive analysis of combined data from six independent peripheral blood transcriptional studies in the Gene Expression Omnibus (GEO) database, covering PTSD and control individuals. Differentially expressed genes (DEGs) were extracted by comparing PTSD patients with control individuals, from which 29 ferroptosis-related genes (FRGs) were cross-matched and obtained. The weighted gene co-expression network analysis (WGCNA), the Extreme Gradient Boosting (XGBoost) model with Bayesian Optimization, and the least absolute shrinkage and selection operator (LASSO) Cox regression were utilized to construct a PTSD prediction model. Single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT revealed the disturbed immunologic state in PTSD high-risk patients.ResultsThree crucial FRGs (ACSL4, ACO1, and GSS) were identified and used to establish a predictive model of PTSD. The receiver operating characteristic (ROC) curve verifies its risk prediction ability. Remarkably, ssGSEA and CIBERSORT demonstrated changes in cellular immunity and antigen presentation depending on the FRGs model.ConclusionThese findings collectively provide evidence that ferroptosis may change immune status in PTSD and be related to the occurrence of PTSD, which may help delineate mechanisms and discover treatment biomarkers for PTSD.

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Iron-induced neuronal damage in a rat model of post-traumatic stress disorder

Cited by 11 publications

References 52 publications

Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts

Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts

Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats

Blood transcriptome analysis: Ferroptosis and potential inflammatory pathways in post-traumatic stress disorder

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