Depression-like phenotypes in mice following common bile duct ligation: Insights into the gut–liver–brain axis via the vagus nerve

Neurobiology of Disease, Год журнала: 2024, Номер 192, С. 106433 - 106433

Опубликована: Фев. 7, 2024

Depression frequently occurs in patients with liver cirrhosis, yet the reasons for this correlation are not fully understood. Dysbiosis of gut microbiota has been implicated depression through gut–brain axis via vagus nerve. This study explored potential role gut–liver–brain nerve depression-like phenotypes mice cirrhosis. These underwent common bile duct ligation (CBDL), a method used to stimulate To assess behaviors, behavioral tests were conducted 10 days following either sham or CBDL surgeries. The displayed symptoms such as splenomegaly, elevated plasma levels interleukin-6 and tumor necrosis factor-α, decreased synaptic proteins prefrontal cortex (PFC), disrupted balance, changes blood metabolites (or lipids). Additionally, there positive negative correlations between relative abundance microbiome data Significantly, these reversed by performing subdiaphragmatic vagotomy. Intriguingly, improved after single injection arketamine, new antidepressant. results suggest that CBDL-induced mediated nerve, arketamine might offer treatment approach cirrhosis patients.

Язык: Английский

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Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions

Journal of Anesthesia and Translational Medicine, Год журнала: 2024, Номер 3(3), С. 65 - 75

Опубликована: Июль 11, 2024

Ketamine, a dissociative anesthetic, is widely utilized in both human and veterinary anesthesia. Its (S)-enantiomer, esketamine, similarly employed for anesthesia analgesia. The anesthetic effects of ketamine esketamine arise from their antagonism the N-methyl-D-aspartate receptor (NMDAR). In field psychiatry, rapid-acting antidepressant properties severe depression have generated significant interest, resulting its increased off-label usage United States (U.S.). 2019, nasal spray received approval use U.S. Europe. However, concerns emerged regarding potential adverse effects, including long-term efficacy, addiction risks, suicide risk clinical settings. contrast, arketamine, (R)-enantiomer ketamine, exhibits superior longer-lasting rodent models depression, with fewer side compared to esketamine. Nevertheless, research on efficacy safety arketamine patients remains limited. This article provides concise exploration historical two enantiomers while also delving into future directions application these fields.

Язык: Английский

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(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6804 - 6804

Опубликована: Июнь 20, 2024

NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative epilepsy, traumatic brain injury, substance abuse disorder (SUD), major depressive (MDD). (S)-ketamine was the first of a novel class antidepressants, rapid-acting to be approved medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development treatment-resistant depression (TRD). compound has demonstrated efficacy multiple animal models. Two clinical studies disclosed TRD bipolar depression. A study by drug sponsor recently failed reach priori endpoints but post hoc analysis revealed efficacy. value supported experimental data humans rodents, showing that it less sedating, does not produce marked psychotomimetic or dissociative effects, than (S)-ketamine, produces models range disorders. mechanisms action antidepressant effects are hypothesized due antagonism and/or non-NMDA mechanisms. We suggest further experimentation with will create improved medicines some disorders underserved current medications.

Язык: Английский

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Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis

Neurobiology of Disease, Год журнала: 2024, Номер 199, С. 106573 - 106573

Опубликована: Июнь 18, 2024

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors chronic social defeat stress (CSDS) model depression. This study investigated whether spleen contributes arketamine CSDS model. We found that splenectomy significantly inhibited arketamine's CSDS-susceptible mice. RNA-sequencing analysis identified oxidative phosphorylation (OXPHOS) pathway prefrontal cortex (PFC) as a key mediator splenectomy's impact on effects. Furthermore, oligomycin A, an inhibitor OXPHOS pathway, reversed suppressive Specific genes within pathways, such COX11, UQCR11 ATP5e, may contribute these inhibitory Notably, transforming growth factor (TGF)-β1, along with appears modulate Additionally, SRI-01138, agonist TGF-β1 receptor, alleviated Subdiaphragmatic vagotomy also counteracted These findings suggest PFC play significant roles arketamine, mediated through spleen-brain axis via vagus nerve.

Язык: Английский

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Depression-like phenotypes in mice with hepatic ischemia/reperfusion injury: A role of gut–microbiota–liver–brain axis via vagus nerve

Journal of Affective Disorders, Год журнала: 2023, Номер 345, С. 157 - 167

Опубликована: Окт. 24, 2023

Язык: Английский

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A role of gut–brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress

Pharmacology Biochemistry and Behavior, Год журнала: 2024, Номер 238, С. 173736 - 173736

Опубликована: Фев. 23, 2024

Язык: Английский

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Prophylactic effects of arketamine, but not hallucinogenic psychedelic DOI nor non-hallucinogenic psychedelic analog lisuride, in lipopolysaccharide-treated mice and mice exposed to chronic restrain stress

Pharmacology Biochemistry and Behavior, Год журнала: 2023, Номер 233, С. 173659 - 173659

Опубликована: Окт. 14, 2023

Язык: Английский

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Gut–brain axis modulation by sudachi peel extract enhances resilience to chronic social defeat stress in mice

Journal of Affective Disorders, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Dietary sulforaphane glucosinolate mitigates depression-like behaviors in mice with hepatic ischemia/reperfusion injury: A role of the gut–liver–brain axis

Journal of Psychiatric Research, Год журнала: 2024, Номер 176, С. 129 - 139

Опубликована: Июнь 5, 2024

Язык: Английский

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Splenic nerve denervation attenuates depression-like behaviors in Chrna7 knock-out mice via the spleen–gut–brain axis

Journal of Affective Disorders, Год журнала: 2024, Номер 362, С. 114 - 125

Опубликована: Июнь 27, 2024

Язык: Английский

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