Prefrontal cortex miR‐874‐3p prevents lipopolysaccharide‐induced depression‐like behavior through inhibition of indoleamine 2,3‐dioxygenase 1 expression in mice

Suento, Willy Jaya; Kunisawa, Kazuo; Wulaer, Bolati; Kosuge, Aika; Iida, Tsubasa; Fujigaki, Suwako; Fujigaki, Hidetsugu; Yamamoto, Yorimasa; Tanra, Andi Jayalangkara; Mouri, Akihiro; Nabeshima, Toshitaka

doi:10.1111/jnc.15222

Cited by 19 publications

(7 citation statements)

References 67 publications

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“…Since indoleamine 2,3-dioxygenase 1 (IDO1) is one of the critical mediators in inflammation-mediated depressive-like behaviors ( Jeon et al ., 2017 ) that is activated by toll-like receptor 4 (TLR4)-related ligands and the IFN family ( Hoyo-Becerra et al ., 2014 ; Suento et al ., 2021 ); we conducted the qRT-PCR of IDO1 as well, which showed similar inhibitory effects by hycanthone ( Supplementary Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

Boo

Gonzales

Remonde

et al. 2022

Biomol Ther (Seoul)

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Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses-and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

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Section: Resultsmentioning

confidence: 99%

Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

Boo

Gonzales

Remonde

et al. 2022

Biomol Ther (Seoul)

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“…Similarly, although rats in Experiment 2 appeared to avoid the CS+ paired with 10 mg/kg KET (and to a lesser extent, 20 mg/kg KET; Figure 3B), this effect was not significant. Even so, conditioned avoidance is typically associated with a reduction in motor activity (Baidoo et al, 2020; Horman et al, 2018), and stimuli that reduce motor activity tend to increase immobility (Lim et al, 2020; Melanson et al, 2021; Suento et al, 2021). Another study conducted in our laboratory (data not shown) also did not find group differences in avoidance responses to a KET CS+ when a more typical place-conditioning protocol (i.e., 4 drug/CS+ and 4 vehicle/CS− pairings, 30 min each) was utilized (Sticht et al, 2010; Thériault et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Conditioned anti-immobility by ketamine: A comparison to escitalopram and bupropion.

Melanson¹,

Wolter²,

Leatham³

et al. 2023

Experimental and Clinical Psychopharmacology

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This study was designed to explore the clinical belief that “set and setting” play an important role in favorable responses to psychedelic agents such as ketamine (KET). In fact, there is evidence in animals that the antidepressant effect of this drug may involve drug–environment interactions in which a context paired with its effects acquires the ability to influence behavior. Therefore, it was investigated in male Sprague–Dawley rats whether exposure to a context paired with the effects of KET, or with the effects of the common antidepressant medications bupropion (BUP) and escitalopram (ESC), could produce an antidepressant-like conditioned response. In Experiment 1, subjects received saline in a vehicle-paired context (denoted as CS−), and 0, 10, or 20 mg/kg KET, 10 mg/kg ESC, or 10 mg/kg BUP in a drug-paired context (denoted as CS+), on 10 alternating days (5 pairings with each context). The rats were then exposed drug free to the CS− and CS+ prior to the assessment of immobility in the forced-swimming test. Experiment 2 assessed approach/avoidance responses induced by the CS− and CS+ in a place-conditioning test. It was found that exposure to the KET CS+ significantly reduced immobility without affecting general locomotor activity in comparison to the SAL CS+ and the BUP CS+, but not the ESC CS+. Moreover, no group differences were observed in the place-conditioning test, indicating that the anti-immobility effect of the KET CS+ was likely not influenced by a conditioned incentive or aversive state. Together, these data suggest that a KET-paired context can elicit a conditioned antidepressant-like response, which may be a mechanism involved in its sustained antidepressant clinical action.

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“…However, a study by Clark et al (2016) has indicated that depression is associated with unexpectedly decreased KP metabolism and cytokine expression in the ventrolateral PFC, which is part of the orbitofrontal cortex region associated with higher emotional function, thus indicating that the brain KP regulation may be region-specific. A recent study has shown that IDO1 expression in mice is upregulated by LPS in the PFC but not in the hippocampus, and microinjection of 1-MT (a potent IDO1 antagonist) or microRNA-874-3p into the PFC downregulates LPS-induced IDO1 expression and ameliorates LPS-induced depression-like behavior, thus revealing that microRNA-874-3p is a novel potential target for the treatment of MDD ( Suento et al, 2020 ). Future research may examine the influence of the gut microbiota on enzymes involved in TRY metabolism along the KP in PFC.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Bibliometric Analysis of the Kynurenine Pathway in Mood Disorders: Focus on Gut Microbiota Research

Zhu

Deng

et al. 2021

Front. Pharmacol.

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Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system.Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field.Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16).Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, “quinolinic acid.” All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were “kynurenine pathway,” “psychoneuroimmunology,” “indoleamine 2,3-dioxygenase,” and “proinflammatory cytokines,” and the most recent focus was “gut-brain axis,” thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field’s research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics “Alzheimer’s disease,” “prefrontal cortex,” and “acid,” were research frontiers.Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field’s hotspots and frontiers, thus facilitating future research.

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Prefrontal cortex miR‐874‐3p prevents lipopolysaccharide‐induced depression‐like behavior through inhibition of indoleamine 2,3‐dioxygenase 1 expression in mice

Cited by 19 publications

References 67 publications

Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

Conditioned anti-immobility by ketamine: A comparison to escitalopram and bupropion.

Comprehensive Bibliometric Analysis of the Kynurenine Pathway in Mood Disorders: Focus on Gut Microbiota Research

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