Reproducible induction of depressive-like behavior in C57BL/6J mice exposed to chronic social defeat stress with a modified sensory contact protocol

Kamimura, Yusuke; Kuwagaki, Erina; Hamano, Sakika; Kobayashi, Mami; Yamada, Yoshimi; Takahata, Yuka; Yoshimoto, Waka; Morimoto, Hirotoshi; Yasukawa, Takeshi; Uozumi, Yoshinobu; Nagasawa, Kohei

doi:10.1016/j.lfs.2021.119821

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…Previous studies with CMS variants stratifying mice for their susceptibility to stressinduced anhedonia showed that it can be associated with expression changes of several molecular and cellular markers of inflammation that are not displayed by resilience to anhedonic animals [22,95,[103][104][105]. For example, CMS-exposed susceptible-to anhedonia-mice revealed significant elevations of COX-1 and IDO expression in the midbrain raphe region, suggesting a possible interaction of neuroinflammation with altered 5-HT transmissionrelation mechanisms [95].…”

Section: Discussionmentioning

confidence: 97%

Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice

Strekalova

Павлов

Трофимов

et al. 2022

IJMS

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The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67. Rat exposure, social defeat, restraints, and tail suspension were used as stressors. We compared the effects of treatment with either the selective COX-2 inhibitor celecoxib (30 mg/kg/day) or citalopram (15 mg/kg/day). For the celecoxib and vehicle-treated mice, the Porsolt test was used. Anhedonic (susceptible) but not non-anhedonic (resilient) animals exhibited elevated COX-2 mRNA levels, increased numbers of COX-2 and Iba-1-positive cells in the dentate gyrus and the CA1 area, and decreased numbers of Ki67-positive cells in the subgranular zone of the hippocampus. Drug treatment decreased the percentage of anhedonic mice, normalized swimming activity, reduced behavioral despair, and improved conditioned fear memory. Hippocampal over-expression of COX-2 is associated with susceptibility to stress-induced anhedonia, and its pharmacological inhibition with celecoxib has antidepressant effects that are similar in size to those of citalopram.

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Section: Discussionmentioning

confidence: 97%

Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice

Strekalova

Павлов

Трофимов

et al. 2022

IJMS

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“…Previous studies with the CMS model, which stratify mice based on their susceptibility to stress-induced anhedonia, have demonstrated that it can be related to changes in the expression of various markers of inflammation that are not shown in rodents resilient to anhedonia [53,57,78,106,107]. For instance, CMS-exposed mice susceptible to anhedonia have shown elevations of Cox-2 expression in the hippocampus and Cox-1 and Ido expression in the midbrain raphe region [77,78].…”

Section: Discussionmentioning

confidence: 99%

Resilience and Vulnerability to Stress-Induced Anhedonia: Unveiling Brain Gene Expression and Mitochondrial Dynamics in a Mouse Chronic Stress Depression Model

Strekalova,

Svirin,

Gorlova

et al. 2023

Biomolecules

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The role of altered brain mitochondrial regulation in psychiatric pathologies, including Major Depressive Disorder (MDD), has attracted increasing attention. Aberrant mitochondrial functions were suggested to underlie distinct inter-individual vulnerability to stress-related MDD syndrome. In this context, insulin receptor sensitizers (IRSs) that regulate brain metabolism have become a focus of recent research, as their use in pre-clinical studies can help to elucidate the role of mitochondrial dynamics in this disorder and contribute to the development of new antidepressant treatment. Here, following 2-week chronic mild stress (CMS) using predation, social defeat, and restraint, MDD-related behaviour and brain molecular markers have been investigated along with the hippocampus-dependent performance and emotionality in mice that received the IRS dicholine succinate (DS). In a sucrose test, mice were studied for the key feature of MDD, a decreased sensitivity to reward, called anhedonia. Based on this test, animals were assigned to anhedonic and resilient-to-stress-induced-anhedonia groups, using a previously established criterion of a decrease in sucrose preference below 65%. Such assignment was based on the fact that none of control, non-stressed animals displayed sucrose preference that would be smaller than this value. DS-treated stressed mice displayed ameliorated behaviours in a battery of assays: sucrose preference, coat state, the Y-maze, the marble test, tail suspension, and nest building. CMS-vulnerable mice exhibited overexpression of the inflammatory markers Il-1β, tnf, and Cox-1, as well as 5-htt and 5-ht2a-R, in various brain regions. The alterations in hippocampal gene expression were the closest to clinical findings and were studied further. DS-treated, stressed mice showed normalised hippocampal expression of the plasticity markers Camk4, Camk2, Pka, Adcy1, Creb-ar, Nmda-2r-ar, and Nmda-2r-s. DS-treated and non-treated stressed mice who were resilient or vulnerable to anhedonia were compared for hippocampal mitochondrial pathway regulation using Illumina profiling. Resilient mice revealed overexpression of the mitochondrial complexes NADH dehydrogenase, succinate dehydrogenase, cytochrome bc1, cytochrome c oxidase, F-type and V-type ATPases, and inorganic pyrophosphatase, which were decreased in anhedonic mice. DS partially normalised the expression of both ATPases. We conclude that hippocampal reduction in ATP synthesis is associated with anhedonia and pro-inflammatory brain changes that are ameliorated by DS.

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“…16S Metagenome Analysis As reported previously, 42) rat colonic feces were obtained under deep anesthesia with the anesthetic mixture, and using their genome DNA, the V3-V4 hypervariable regions of 16S ribosomal RNA were amplified and sequenced on an Illumina Miseq platform (Illumina, CA, U.S.A.). Bioinformatic analyses were performed with a QIIME II pipeline (version 2021.2) with SILVA data base release 132.…”

Section: Methodsmentioning

confidence: 99%

Alteration of Sweet and Bitter Taste Sensitivity with Development of Glucose Intolerance in Non-insulin-Dependent Diabetes Mellitus Model OLETF Rats

Tanaka,

Mogi,

Fujita

et al. 2024

Biological & Pharmaceutical Bulletin

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Patients with diabetes exhibit altered taste sensitivity, but its details have not been clarified yet. Here, we examined alteration of sweet taste sensitivity with development of glucose intolerance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of non-insulin-dependent diabetes mellitus. Compared to the cases of Long Evans Tokushima Otsuka (LETO) rats as a control, glucose tolerance of OLETF rats decreased with aging, resulting in development of diabetes at 36-weeks-old. In brief-access tests with a mixture of sucrose and quinine hydrochloride, OLETF rats at 25 or more-weeks-old seemed to exhibit lower sweet taste sensitivity than age-matched LETO ones, but the lick ratios of LETO, but not OLETF, rats for the mixture and quinine hydrochloride solutions decreased and increased, respectively, aging-dependently. Expression of sweet taste receptors, T1R2 and T1R3, in circumvallate papillae (CP) was almost the same in LETO and OLETF rats at 10-and 40-weeks-old, while expression levels of a bitter taste receptor, T2R16, were greater in 40-weeks-old rats than in 10-weeks-old ones in both strains. There was no apparent morphological alteration in taste buds in CP between 10-and 40-weeks-old LETO and OLETF rats. Metagenomic analysis of gut microbiota revealed strain-and aging-dependent alteration of mucus layer-regulatory microbiota. Collectively, we concluded that the apparent higher sweet taste sensitivity in 25 or more-weeks-old OLETF rats than in age-matched LETO rats was due to the aging-dependent increase of bitter taste sensitivity in LETO rats with alteration of the gut microbiota.

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Reproducible induction of depressive-like behavior in C57BL/6J mice exposed to chronic social defeat stress with a modified sensory contact protocol

Cited by 12 publications

References 35 publications

Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice

Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice

Resilience and Vulnerability to Stress-Induced Anhedonia: Unveiling Brain Gene Expression and Mitochondrial Dynamics in a Mouse Chronic Stress Depression Model

Alteration of Sweet and Bitter Taste Sensitivity with Development of Glucose Intolerance in Non-insulin-Dependent Diabetes Mellitus Model OLETF Rats

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