Single prolonged stress induces post-traumatic stress disorder-like characteristics in ICR mice

Tanaka, Kenichi; Yagi, Takao; Nanba, Takeshi; Asanuma, Masato

doi:10.1254/jpssuppl.wcp2018.0_po3-1-41

Cited by 5 publications

(5 citation statements)

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“…As far as our knowledge goes, there are no previous records on the effects of SPS on spatial working memory in rats. In a recent study on mice, it was shown that SPS could not change the alteration behavior ratio in a Y-maze model of working memory (Tanaka et al ., 2018). In our previous study, systemic NaBu improved the spatial reference memory in rats (Mohammadi-Farani et al ., 2020).…”

Section: Discussionmentioning

confidence: 99%

Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Mohammadi-Farani¹,

Limoee

Shirooie³

2021

Behavioural Pharmacology

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It is believed that impaired extinction of fear memories is an underlying cause for the development of posttraumatic stress disorder (PTSD). Histone deacetylases (HDAC) are enzymes that modulate extinction by changing the chromatin structure and altering protein synthesis in the brain. Studies show that stress modifies both HDAC activity and cerebral cholinergic neurotransmission. The present work aims to evaluate the effect of sodium butyrate (NaBu), an HDAC inhibitor, on behavioral markers of extinction and biochemical changes in HDAC and acetylcholinesterase activity in the hippocampus. NaBu was administered for 7 days in a group of rats that were exposed to single prolonged stress (SPS), as a model for PTSD. Contextual fear conditioning was performed on the 8th day, and fear extinction was measured in the next 4 consecutive days. Other behavioral tests to measure anxiety, locomotor activity and working memory were performed for further interpretation of the results. Hippocampal acetylcholinesterase and HDAC activity were also measured through biochemical tests. Behavioral results showed that treatment with NaBu can reverse the SPS-induced extinction deficits. Biochemical data indicated that while SPS induced overactivity in hippocampal HDAC, it decreased acetylcholinesterase activity in the region. Both effects were reversed after NaBu treatment. It seems that at least part of extinction deficiency in SPS exposed rats is related to hypoacetylation of acetylcholinesterase in the hippocampus. Preemptive therapy with an HDAC inhibitor reverses this process and is worth further evaluation as a possible therapeutic approach in PTSD.

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Section: Discussionmentioning

confidence: 99%

Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Mohammadi-Farani¹,

Limoee

Shirooie³

2021

Behavioural Pharmacology

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“…Given that SPS was optimized for adult rats, which differ from mice in morphology of the brain, key features of stress response systems, and the effects of stress across domains including cognition, the application of SPS to mice and the translation of the results obtained in rats requires careful consideration (Armario and Castellanos, 1984;Schöner et al, 2017). There have been several studies that have modified SPS for application in mice (e.g., Wang et al, 2012;Yu et al, 2013;Tanaka et al, 2018;Teutsch et al, 2018); however, only one modified protocol has been demonstrated to replicate key outcome effects of the rat SPS model (Perrine et al, 2016). The mouse-SPS model described by Perrine et al yields an extinction retention deficit and glucocorticoid receptor expression pattern similar to those detected following SPS in adult male rats.…”

Section: Methodological Considerations For Sps In Micementioning

confidence: 99%

“…stressor (Yu et al, 2013), adding conditioned fear using foot shocks (Wang et al, 2012), and increasing the water temperature during the forced swim stressor (Tanaka et al, 2018;Teutsch et al, 2018).…”

Section: Pop-out 3: Research Personnel As Part Of An Experimental Contextmentioning

confidence: 99%

Systematic Review and Methodological Considerations for the Use of Single Prolonged Stress and Fear Extinction Retention in Rodents

Ferland‐Beckham

Chaby

Daskalakis

et al. 2021

Front. Behav. Neurosci.

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Posttraumatic stress disorder (PTSD) is a mental health condition triggered by experiencing or witnessing a terrifying event that can lead to lifelong burden that increases mortality and adverse health outcomes. Yet, no new treatments have reached the market in two decades. Thus, screening potential interventions for PTSD is of high priority. Animal models often serve as a critical translational tool to bring new therapeutics from bench to bedside. However, the lack of concordance of some human clinical trial outcomes with preclinical animal efficacy findings has led to a questioning of the methods of how animal studies are conducted and translational validity established. Thus, we conducted a systematic review to determine methodological variability in studies that applied a prominent animal model of trauma-like stress, single prolonged stress (SPS). The SPS model has been utilized to evaluate a myriad of PTSD-relevant outcomes including extinction retention. Rodents exposed to SPS express an extinction retention deficit, a phenotype identified in humans with PTSD, in which fear memory is aberrantly retained after fear memory extinction. The current systematic review examines methodological variation across all phases of the SPS paradigm, as well as strategies for behavioral coding, data processing, statistical approach, and the depiction of data. Solutions for key challenges and sources of variation within these domains are discussed. In response to methodological variation in SPS studies, an expert panel was convened to generate methodological considerations to guide researchers in the application of SPS and the evaluation of extinction retention as a test for a PTSD-like phenotype. Many of these guidelines are applicable to all rodent paradigms developed to model trauma effects or learned fear processes relevant to PTSD, and not limited to SPS. Efforts toward optimizing preclinical model application are essential for enhancing the reproducibility and translational validity of preclinical findings, and should be conducted for all preclinical psychiatric research models.

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“…These procedures guaranteed PTSD-like behaviors in rats for a prolonged period of time. However, it is difficult to reproduce this model in mice with the same stimulation method [42]. Several modified SPS models have appeared in other studies, such as single-cage feeding after SPS, exposing mice to dirty rat bedding after SPS, and giving electric shocks after SPS (SPS&S) [23,[43][44][45].…”

Section: Discussionmentioning

confidence: 99%

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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Single prolonged stress induces post-traumatic stress disorder-like characteristics in ICR mice

Cited by 5 publications

References 0 publications

Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Sodium butyrate enhances fear extinction and rescues hippocampal acetylcholinesterase activity in a rat model of posttraumatic stress disorder

Systematic Review and Methodological Considerations for the Use of Single Prolonged Stress and Fear Extinction Retention in Rodents

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

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