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  • Springer Science and Business Media LLC  (21)
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  • Springer Science and Business Media LLC  (21)
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  • 1
    Online Resource
    Online Resource
    Microglial depletion and abnormalities in gut microbiota composition and short-chain fatty acids in mice after repeated administration of colony stimulating factor 1 receptor inhibitor PLX5622
    Springer Science and Business Media LLC ; 2022
    In:  European Archives of Psychiatry and Clinical Neuroscience Vol. 272, No. 3 ( 2022-04), p. 483-495
    Details
    In: European Archives of Psychiatry and Clinical Neuroscience, Springer Science and Business Media LLC, Vol. 272, No. 3 ( 2022-04), p. 483-495
    Type of Medium: Online Resource
    ISSN: 0940-1334 , 1433-8491
    URL: Article
    DOI: 10.1007/s00406-021-01325-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2793981-9
    detail.hit.zdb_id: 1459045-1
    SSG: 2,1
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  • 2
    Online Resource
    Online Resource
    Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-08-02)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-08-02)
    Abstract: Accumulating evidence suggests a role of the ephrin receptor EphA4 and the downstream protein ephexin1 in synaptic plasticity, which is implicated in depression. We examined whether EphA4–ephexin1 signaling plays a role in the pathophysiology of depression, and the antidepressant-like effect of EphA4 inhibitor rhynchophylline. We found increased ratios of p-EphA4/EphA4 and p-ephexin1/ephexin1 in the prefrontal cortex (PFC) and hippocampus but not in the nucleus accumbens (NAc), of susceptible mice after social defeat stress. Furthermore, the p-EphA4/EphA4 ratio was higher in the parietal cortex of depressed patients compared with controls. Systemic administration of rhynchophylline, produced a rapid antidepressant-like effect in a social defeat stress model by inhibiting EphA4–ephexin1 signaling and activating brain-derived neurotrophic factor-TrkB signaling in the PFC and hippocampus. Pretreatment with rhynchophylline before each social defeat stress could prevent the onset of the depression-like phenotype after repeated social defeat stress. Overexpression of EphA4 in the medial PFC owing to infection with an EphA4 adeno-associated virus caused the depression-like phenotype 3 weeks later and rhynchophylline had a rapid antidepressant-like effect in these mice. These findings suggest that increased EphA4–ephexin1 signaling in the PFC plays a role in the pathophysiology of depression.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-017-07325-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 3
    Online Resource
    Online Resource
    Possible role of the gut microbiota–brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model
    Springer Science and Business Media LLC ; 2017
    In:  Translational Psychiatry Vol. 7, No. 12 ( 2017-12-18)
    Details
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 7, No. 12 ( 2017-12-18)
    Abstract: Accumulating evidence suggests that the gut microbiota–brain axis plays a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. ( R )-ketamine has a greater potency and longer-lasting antidepressant effects than ( S )-ketamine. Here, we investigated whether the gut microbiota plays a role in the antidepressant effects of these two ketamine enantiomers. The role of the gut microbiota in the antidepressant effects of ketamine enantiomers in a chronic social defeat stress (CSDS) model of depression was examined using 16S ribosomal RNA gene sequencing of fecal samples. At the phylum level, CSDS-susceptible mice showed alterations in the levels of Tenericutes and Actinobacteria ; however, neither ketamine enantiomers influenced these alterations. At the class level, both ketamine enantiomers significantly attenuated the increase in the levels of Deltaproteobacteria in the susceptible mice after CSDS. Furthermore, ( R )-ketamine, but not ( S )-ketamine, significantly attenuated the reduction in the levels of Mollicutes in the susceptible mice. At the genus level, both ketamine enantiomers significantly attenuated the decrease in the levels of Butyricimonas in the susceptible mice. Notably, ( R )-ketamine was more potent than ( S )-ketamine at reducing the levels of Butyricimonas in the susceptible mice. In conclusion, this study suggests that the antidepressant effects of two enantiomers of ketamine in CSDS model may be partly mediated by the restoration of the gut microbiota. Furthermore, the specific effect of ( R )-ketamine on the levels of Mollicutes and Butyricimonas may explain its robust antidepressant action.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    URL: Article
    DOI: 10.1038/s41398-017-0031-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2609311-X
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  • 4
    Online Resource
    Online Resource
    Nuclear factor of activated T cells 4 in the prefrontal cortex is required for prophylactic actions of (R)-ketamine
    Springer Science and Business Media LLC ; 2022
    In:  Translational Psychiatry Vol. 12, No. 1 ( 2022-01-21)
    Details
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-01-21)
    Abstract: ( R, S )-ketamine has prophylactic antidepressant-like effects in rodents; however, the precise molecular mechanisms underlying its action remain unknown. Using RNA-sequencing analysis, we searched novel molecular target(s) that contribute to the prophylactic effects of ( R )-ketamine, a more potent enantiomer of ( R, S )-ketamine. Pretreatment with ( R )-ketamine (10 mg/kg, 6 days before) significantly ameliorated body weight loss, splenomegaly, and increased immobility time of forced swimming test in lipopolysaccharide (LPS: 1.0 mg/kg)-treated mice. RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent IPA (Ingenuity Pathway Analysis) revealed that the nuclear factor of activated T cells 4 (NFATc4) signaling might contribute to sustained prophylactic effects of ( R )-ketamine. Quantitative RT-PCR confirmed that ( R )-ketamine significantly attenuated the increased gene expression of NFATc4 signaling ( Nfatc4, Cd4, Cd79b, H2-ab1 , H2-aa ) in the PFC of LPS-treated mice. Furthermore, pretreatment with NFAT inhibitors (i.e., NFAT inhibitor and cyclosporin A) showed prophylactic effects in the LPS-treated mice. Similar to ( R )-ketamine, gene knockdown of Nfatc4 gene by bilateral injection of adeno-associated virus (AAV) into the mPFC could elicit prophylactic effects in the LPS-treated mice. In conclusion, our data implicate a novel NFATc4 signaling pathway in the PFC underlying the prophylactic effects of ( R )-ketamine for inflammation-related depression.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    URL: Article
    DOI: 10.1038/s41398-022-01803-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2609311-X
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  • 5
    Online Resource
    Online Resource
    Splenic NKG2D confers resilience versus susceptibility in mice after chronic social defeat stress: beneficial effects of (R)-ketamine
    Springer Science and Business Media LLC ; 2021
    In:  European Archives of Psychiatry and Clinical Neuroscience Vol. 271, No. 3 ( 2021-04), p. 447-456
    Details
    In: European Archives of Psychiatry and Clinical Neuroscience, Springer Science and Business Media LLC, Vol. 271, No. 3 ( 2021-04), p. 447-456
    Abstract: The spleen is a large immune organ that plays a key role in the immune system. The precise molecular mechanisms underlying the relationship between the spleen and stress-related psychiatric disorders are unknown. Here we investigated the role of spleen in stress-related psychiatric disorders. FACS analysis was applied to determine the contribution of the spleen to susceptibility and resilience in mice that were subjected to chronic social defeat stress (CSDS). We found a notable increase in splenic volume and weight in CSDS-susceptible mice compared to control (no CSDS) mice and CSDS-resilient mice. The number of granulocytes, but not of T cells and B cells, in the spleen of susceptible mice was higher than in the spleen of both control and resilient mice. Interestingly, NKG2D (natural killer group 2, member D) expression in the spleen of CSDS-susceptible mice was higher than that in control mice and CSDS-resilient mice. In addition, NKG2D expression in the spleen of patients with depression was higher than that in controls. Both increased splenic weight and increased splenic NKG2D expression in CSDS-susceptible mice were ameliorated after a subsequent administration of ( R )-ketamine. The present findings indicate a novel role of splenic NKG2D in stress susceptibility versus resilience in mice subjected to CSDS. Furthermore, abnormalities in splenic functions in CSDS-susceptible mice were ameliorated after subsequent injection of ( R )-ketamine. Thus, the brain–spleen axis might, at least in part, contribute to the pathogenesis of stress-related psychiatric disorders such as depression.
    Type of Medium: Online Resource
    ISSN: 0940-1334 , 1433-8491
    URL: Article
    DOI: 10.1007/s00406-019-01092-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2793981-9
    detail.hit.zdb_id: 1459045-1
    SSG: 2,1
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  • 6
    Online Resource
    Online Resource
    (R)-Ketamine attenuates LPS-induced endotoxin-derived delirium through inhibition of neuroinflammation
    Springer Science and Business Media LLC ; 2021
    In:  Psychopharmacology Vol. 238, No. 10 ( 2021-10), p. 2743-2753
    Details
    In: Psychopharmacology, Springer Science and Business Media LLC, Vol. 238, No. 10 ( 2021-10), p. 2743-2753
    Type of Medium: Online Resource
    ISSN: 0033-3158 , 1432-2072
    URL: Article
    DOI: 10.1007/s00213-021-05889-6
    RVK:
    CL 1000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2066933-1
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration
    Springer Science and Business Media LLC ; 2020
    In:  Translational Psychiatry Vol. 10, No. 1 ( 2020-06-09)
    Details
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-06-09)
    Abstract: The vagus nerve plays a role in the cross talk between the brain and gut microbiota, which could be involved in depression. The subdiaphragmatic vagus nerve serves as a major modulatory pathway between the brain and gut microbiota. Here, we investigated the effects of subdiaphragmatic vagotomy (SDV) on the depression-like phenotype and the abnormal composition of gut microbiota in mice after lipopolysaccharide (LPS) administration. LPS caused a depression-like phenotype, inflammation, increase in spleen weight, and downregulation of synaptic proteins in the medial prefrontal cortex (mPFC) in the sham-operated mice. In contrast, LPS did not produce a depression-like phenotype and downregulated synaptic proteins in the mPFC after SDV. The spleen weight and plasma levels of pro-inflammatory cytokines in the SDV + LPS group were lower than those of the sham + LPS group. Interestingly, there were positive correlations between the plasma levels of pro-inflammatory cytokines and spleen weight, suggesting a relationship between inflammatory events and spleen weight. Furthermore, LPS led to significant alterations in gut microbiota diversity in sham-operated mice, but not SDV-operated mice. In an unweighted UniFrac PCoA, the dots representing the sham + LPS group were located far away from the dots representing the other three groups. Our results suggest that LPS produces a depression-like phenotype, increases spleen weight, triggers inflammation, downregulates synaptic proteins in the mPFC, and leads to abnormal composition of gut microbiota via the subdiaphragmatic vagus nerve. It is likely that the vagus nerve plays a crucial role in the brain–gut–microbiota axis.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    URL: Article
    DOI: 10.1038/s41398-020-00878-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2609311-X
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  • 8
    Online Resource
    Online Resource
    A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice
    Springer Science and Business Media LLC ; 2022
    In:  Translational Psychiatry Vol. 12, No. 1 ( 2022-09-28)
    Details
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-09-28)
    Abstract: ( R,S )-ketamine is known to elicit persistent prophylactic effects in rodent models of depression. However, the precise molecular mechanisms underlying its action remain elusive. Using RNA-sequencing analysis, we searched for novel molecular target(s) that contribute to the prophylactic effects of ( R )-ketamine, a more potent enantiomer of ( R,S )-ketamine in chronic restraint stress (CRS) model. Pretreatment with ( R )-ketamine (10 mg/kg, 1 day before CRS) significantly ameliorated body weight loss, increased immobility time of forced swimming test, and decreased sucrose preference of sucrose preference test in CRS-exposed mice. RNA-sequencing analysis of prefrontal cortex (PFC) revealed that several miRNAs such as miR-132-5p might contribute to sustained prophylactic effects of ( R )-ketamine. Methyl CpG binding protein 2 (MeCP2) is known to regulate brain-derived neurotrophic factor (BDNF) expression. Quantitative RT-PCR confirmed that ( R )-ketamine significantly attenuated altered expression of miR-132-5p and its regulated genes ( Bdnf, Mecp2, Tgfb1, Tgfbr2 ) in the PFC of CRS-exposed mice. Furthermore, ( R )-ketamine significantly attenuated altered expression of BDNF, MeCP2, TGF-β1 (transforming growth factor β1), and synaptic proteins (PSD-95, and GluA1) in the PFC of CRS-exposed mice. Administration of agomiR-132-5p decreased the expression of Bdnf and Tgfb1 in the PFC, resulting in depression-like behaviors. In contrast, administration of antagomiR-132-5p blocked the increased expression of miR-132-5p and decreased expression of Bdnf in the PFC of CRS-exposed mice, resulting in antidepressant-like effects. In conclusion, our data show a novel role of miR-132-5p in the PFC underlying depression-like phenotypes in CRS model and the sustained prophylactic effects of ( R )-ketamine.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    URL: Article
    DOI: 10.1038/s41398-022-02192-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2609311-X
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  • 9
    Online Resource
    Online Resource
    Repeated intermittent administration of (R)-ketamine during juvenile and adolescent stages prevents schizophrenia-relevant phenotypes in adult offspring after maternal immune activation: a role of TrkB signaling
    Springer Science and Business Media LLC ; 2022
    In:  European Archives of Psychiatry and Clinical Neuroscience Vol. 272, No. 4 ( 2022-06), p. 693-701
    Details
    In: European Archives of Psychiatry and Clinical Neuroscience, Springer Science and Business Media LLC, Vol. 272, No. 4 ( 2022-06), p. 693-701
    Abstract: Maternal immune activation (MIA) plays a role in the etiology of schizophrenia. MIA by prenatal exposure of polyinosinic:polycytidylic acid [poly(I:C)] in rodents caused behavioral and neurobiological changes relevant to schizophrenia in adult offspring. We investigated whether the novel antidepressant ( R )-ketamine could prevent the development of psychosis-like phenotypes in adult offspring after MIA. We examined the effects of ( R )-ketamine (10 mg/kg/day, twice weekly for 4 weeks) during juvenile and adolescent stages (P28–P56) on the development of cognitive deficits, loss of parvalbumin (PV)-immunoreactivity in the medial prefrontal cortex (mPFC), and decreased dendritic spine density in the mPFC and hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, we examined the role of TrkB in the prophylactic effects of ( R )-ketamine. Repeated intermittent administration of ( R )-ketamine during juvenile and adolescent stages significantly blocked the development of cognitive deficits, reduced PV-immunoreactivity in the prelimbic (PrL) of mPFC, and decreased dendritic spine density in the PrL of mPFC, CA3 and dentate gyrus of the hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, pretreatment with ANA-12 (TrkB antagonist: twice weekly for 4 weeks) significantly blocked the beneficial effects of ( R )-ketamine on cognitive deficits of adult offspring after prenatal poly(I:C) exposure. These data suggest that repeated intermittent administration of ( R )-ketamine during juvenile and adolescent stages could prevent the development of psychosis in adult offspring after MIA. Therefore, ( R )-ketamine would be a potential prophylactic drug for young subjects with high-risk for psychosis.
    Type of Medium: Online Resource
    ISSN: 0940-1334 , 1433-8491
    URL: Article
    DOI: 10.1007/s00406-021-01365-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2793981-9
    detail.hit.zdb_id: 1459045-1
    SSG: 2,1
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  • 10
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    Online Resource
    Gut–microbiota–brain axis in the vulnerability to psychosis in adulthood after repeated cannabis exposure during adolescence
    Springer Science and Business Media LLC ; 2022
    In:  European Archives of Psychiatry and Clinical Neuroscience Vol. 272, No. 7 ( 2022-10), p. 1297-1309
    Details
    In: European Archives of Psychiatry and Clinical Neuroscience, Springer Science and Business Media LLC, Vol. 272, No. 7 ( 2022-10), p. 1297-1309
    Type of Medium: Online Resource
    ISSN: 0940-1334 , 1433-8491
    URL: Article
    DOI: 10.1007/s00406-022-01437-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2793981-9
    detail.hit.zdb_id: 1459045-1
    SSG: 2,1
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