Behavioural Brain Research最新文献

{"title":"Post acquisition 5-HT6 receptor agonist EMD386088 administration impairs consolidation of a spatial discrimination in mice","authors":"Jasmine Alyssa Robinson ,&nbsp;Dionisio Antonio Amodeo","doi":"10.1016/j.bbr.2025.115489","DOIUrl":"10.1016/j.bbr.2025.115489","url":null,"abstract":"<div><div>The serotonergic system has been known to play an important role in acquisition, consolidation and retrieval of memories. Specific serotonin (5-HT) receptor modulation can effectively impact the consolidation of these memories. Determining how specific 5-HT receptor modulation can impact consolidation of spatial memories has been examined, although the 5-HT6 receptor has not been a focus of such studies. The current study aims examine the impact of 5-HT6 receptor agonist EMD386088 administration on the consolidation of a probabilistic spatial discrimination. Female and male C57BL/6 J mice were trained on a probabilistic spatial discrimination then received acute systemic injections of either 0, 1 or 5 mg/kg EMD386088 immediately after reaching learning criterion for the spatial discrimination, targeting the consolidation window. During the retention test, both doses of 1 mg/kg and 5 mg/kg significantly impaired performance in both female and male C57BL/6 J mice. Although there were no significant differences between the two doses, mice treated with either dose of EMD386088 required significantly more trials to reach retention criterion compared to vehicle-treated mice. These learning impairments were independent of effects on locomotor measures due to the comparable trials per min across all treatment groups during both the acquisition and retention tests. The current findings demonstrate the potential sensitivity of treatment timing in the application of novel therapeutics aimed at stimulating 5-HT6 receptors and their impact on memory.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"484 ","pages":"Article 115489"},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Running to remember: The effects of exercise on perineuronal nets, microglia, and hippocampal angiogenesis in female and male mice","authors":"Madeleine G. Maheu ,&nbsp;Noah James ,&nbsp;Zach Clark ,&nbsp;Alex Yang ,&nbsp;Ridhi Patel ,&nbsp;Shawn M. Beaudette ,&nbsp;Rebecca E.K. MacPherson ,&nbsp;Paula Duarte-Guterman","doi":"10.1016/j.bbr.2025.115478","DOIUrl":"10.1016/j.bbr.2025.115478","url":null,"abstract":"<div><div>Exercise is accepted as a positive health behaviour; however, the mechanisms of exercise on neuroprotection and cognitive health are not completely understood. The purpose of this study was to explore the neurobiological benefits of chronic treadmill exercise in female and male mice through its role in microglial content and morphology, cerebral vascularization, and perineuronal net (PNN) expression. We further examined how these neurobiological changes relate to spatial memory outcomes. Adult mice were assigned to a sedentary or treadmill exercise group for eight weeks. During the final week, all mice were trained on a spatial memory task (Barnes maze) and brains were collected for immunohistochemistry. Exercised mice made fewer errors than sedentary mice during the first two days of training and probe trial. Females, regardless of exercise training, made fewer errors during Barnes maze training and demonstrated a greater frequency of spatial strategy use compared to males. Exercised mice, regardless of sex, had fewer PNNs in the dentate gyrus of the hippocampus compared to sedentary controls. The number of PNNs in the dorsal dentate gyrus was positively correlated with total errors during training. During the probe, greater errors correlated with more PNNs among the exercised group only. Microglia count and cerebral vascularization were not affected by exercise, although proportions of microglia type (ameboid, stout/thick, and thick/thin) were regulated by exercise in the ventral dentate gyrus. We conclude that exercise decreases PNNs in the dentate gyrus in both sexes and this may be related to better spatial learning and memory.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"484 ","pages":"Article 115478"},"PeriodicalIF":2.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The alteration of glutamate involved in the brain of Parkinson's disease patients using glutamate chemical exchange saturation transfer (GluCEST)","authors":"Miaomiao Liu ,&nbsp;Minglong Li ,&nbsp;Hailing Du ,&nbsp;Donghao Xu ,&nbsp;Jing Wang ,&nbsp;Qingfa Ren ,&nbsp;Rui Wang ,&nbsp;He Gong ,&nbsp;Yuwei Liu ,&nbsp;Kai Qi ,&nbsp;Jin Tao ,&nbsp;Shuyuan Xia ,&nbsp;Hongcai Wang ,&nbsp;Xianglin Li ,&nbsp;Quanyuan Liu","doi":"10.1016/j.bbr.2025.115484","DOIUrl":"10.1016/j.bbr.2025.115484","url":null,"abstract":"<div><div>Increased levels of glutamate, a novel regulator of neuroinflammation, is involved in the pathogenesis of Parkinson's disease (PD). Although glutamate chemical exchange saturation transfer (GluCEST) is widely used in central nervous system (CNS) disorders, it has been less commonly used in clinical practice for PD. Here, to explore the clinical significance of variations in glutamate levels in the striatum and thalamus in PD, we included forty-nine PD patients and forty-four healthy controls (HCs). Glutamate levels were analyzed by performing magnetization transfer ratio asymmetry (MTRasym) using GluCEST data. Four regions of interest (ROIs) were manually outlined on GluCEST images, and MTRasym values were calculated for each. FreeSurfer was used to calculate the volumes. We found that MTRasym values in the striatum and thalamus were elevated in PD. Variations in MTRasym values were correlated with motor scores. It has been found that the volume of the left pallidal nucleus were reduced in PD. The glutamate levels in the striatum and thalamus were significantly different from those in HCs and associated with disease progression. Collectively, glutamate metabolic abnormalities may be present in PD pathophysiology and associated with disease progression. GluCEST imaging may have potential to become an imaging technology for measuring glutamate alterations in the striatum and thalamus in PD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115484"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing multilingual speakers’ language processing through functional near-infrared spectroscopy (fNIRS)","authors":"Fizza Farrukh ,&nbsp;Hammad Nazeer ,&nbsp;Hamza Shabbir Minhas ,&nbsp;Noman Naseer ,&nbsp;Farzan Majeed Noori","doi":"10.1016/j.bbr.2025.115485","DOIUrl":"10.1016/j.bbr.2025.115485","url":null,"abstract":"<div><div>Multilinguals’ navigation through three or more language systems utilizing one cognitive system is a phenomenon of recent interest. Few functional near-infrared spectroscopy (fNIRS) studies have focused on brain activations concerning multilinguals. The present study uses picture-naming and fNIRS technique to explore the prefrontal brain activations amongst neurotypical multilinguals belonging to four major provinces of Pakistan. The 26 right-handed participants utilize their native language (Punjabi, Pushto, Sindhi or Balochi), first language (Urdu) and second language (English) distinctively in the experiment. Brain imaging results demonstrate a significant activation of the right prefrontal cortex among the multilingual adults along with left laterality. Moreover, results indicate significant activation of channels demonstrating heavier cognitive load with English in comparison to first or native language(s). The paper suggests that right dorsolateral prefrontal cortex and right medial prefrontal cortex play a significant role in language processing alongside the left prefrontal cortex, exemplifying that peripheral activation during word retrieval, processing and production is a possibility.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"484 ","pages":"Article 115485"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cannabinoid CB2 receptor mediates the analgesic effects of Cannabis sativa extract in a rat model of neuropathic pain","authors":"Samad Nazemi ,&nbsp;Atena Adel-Rastkhiz ,&nbsp;Marzieh Kafami ,&nbsp;Bahareh Amin ,&nbsp;Mohammad Mohammad-Zadeh ,&nbsp;Mohammad-Shafi Mojadadi","doi":"10.1016/j.bbr.2025.115482","DOIUrl":"10.1016/j.bbr.2025.115482","url":null,"abstract":"<div><div>Neuropathic pain (NP) is a complex and debilitating condition that is often refractory to currently available analgesic medications. <em>Cannabis sativa</em> extract (CSE) has been reported to exhibit analgesic properties across various pain models; however, the underlying mechanisms of action are not fully understood. This study aimed to investigate the involvement of the cannabinoid CB2 receptor in mediating the analgesic effects of CSE in a rat model of NP, where NP was induced in male Wistar rats through chronic constriction injury (CCI) of the sciatic nerve. Rats were randomly allocated into four groups: (1) Sham + vehicle, (2) CCI + vehicle, (3) CCI + CSE, and (4) CCI + CSE + AM630 (a CB2 receptor antagonist). CSE was administered intraperitoneally at a dosage of 30 mg/kg once daily for 7 days, starting from day 7 to day 13 post-CCI surgery. To assess the involvement of the CB2 receptor, 7 µg of AM630 was administered intrathecally to the rats in group 4, 30 minutes before the CSE injections. Mechanical allodynia and thermal hyperalgesia were assessed using the von Frey filament and hot plate tests, respectively, at baseline (day 0) and on days 3, 7, 10, and 14 after surgery. Additionally, at the end of the study period (day 14), the expression level of <em>Iba1</em> and <em>GFAP</em> genes was quantified in the lumbar enlargement tissues using real-time PCR. The results demonstrated that CCI surgery induced mechanical allodynia and thermal hyperalgesia, along with the upregulation of <em>Iba1</em> and <em>GFAP</em> genes in the vehicle-treated CCI group. Treatment with CSE significantly mitigated both allodynia and hyperalgesia and downregulated the expression of <em>Iba1</em> and <em>GFAP</em> genes compared to the CCI + vehicle group. Furthermore, the administration of the CB2 receptor antagonist AM630 not only robustly blocked the antinociceptive effects of CSE but also reversed the significant downregulation of <em>Iba1</em> and <em>GFAP</em> gene expression in the lumbar enlargement tissues. These findings highlight the novel role of the CB2 receptor in mediating the analgesic effects of CSE, providing new insights into the potential therapeutic mechanisms of CSE in neuropathic pain management.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115482"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimenters' sex modulates anxiety-like behavior, contextual fear, and microglial oxytocin transcription in mice","authors":"Mai Sakai ,&nbsp;Zhiqian Yu ,&nbsp;Rosanne Picotin ,&nbsp;Tomoko Kasahara ,&nbsp;Yoshie Kikuchi ,&nbsp;Chiaki Ono ,&nbsp;Mizuki Hino ,&nbsp;Yasuto Kunii ,&nbsp;Yuko Maejima ,&nbsp;Kenju Shimomura ,&nbsp;Miharu Nakanishi ,&nbsp;Takaaki Abe ,&nbsp;Hatsumi Yoshii ,&nbsp;Hiroaki Tomita","doi":"10.1016/j.bbr.2025.115480","DOIUrl":"10.1016/j.bbr.2025.115480","url":null,"abstract":"<div><div>Oxytocin (OXT) is a neuropeptide known for modulating anxiety and fear memory. We have reported that microglial cytokine regulates contextual fear memory and that microglial OXT positively correlates with cytokine secretion. However, the relationship between contextual fear memory and microglial OXT expression remains unclear. We evaluated whether experimental handling minimizes anxiety-like behaviors through microglial OXT expression and its effects on contextual fear response in a sex-dependent manner. Male and female mice were cup-handled for seven days by male or female experimenters (four groups: male mice with or without handling and female mice with or without handling). Post-handling anxiety-like behavior was assessed using elevated plus maze (EPM) and light-dark box (LDB) tests. Microglial <em>Oxt</em> transcription was evaluated using real-time PCR following handling and footshock. Our results showed that handling by female experimenters induced anxiolytic behaviors in the EPM and LDB and microglial <em>Oxt</em> transcripts in male mice but did not show a direct causal relationship. After handling by male experimenters, male mice exhibited stronger conditional freezing responses than female mice. In contrast, female mice exhibited significantly weaker freezing, independent of <em>Oxt</em> transcription in the microglia and the paraventricular hypothalamic nucleus. These findings suggest that handling influences anxiety and microglial <em>Oxt</em> expression, while conditional freezing reflects a sex-dependent effect by experimenter sex.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115480"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent social isolation increases social behavior in Wistar rats: Role of post-weaning isolation housing on Social Familiarity-induced Anxiolysis (SoFiA) and social memory in adulthood","authors":"Andrew R. Burke ,&nbsp;Cristian Bernabe ,&nbsp;Amy Dietrich ,&nbsp;Rebecca Daugherty ,&nbsp;Jodi L. Lukkes ,&nbsp;William A. Truitt","doi":"10.1016/j.bbr.2025.115481","DOIUrl":"10.1016/j.bbr.2025.115481","url":null,"abstract":"<div><div>Social connectedness is a critical part of adolescent development. Social support provides a robust facilitator for managing anxiety disorders that afflict nearly 1⁄3 of the U.S. adult population at some point in life. Consequently, it is important to understand the neurobiological mechanisms underlying the impact of social affiliation, or lack thereof, on treating or causing maladaptive anxiety states. In the current experiment, we manipulated the housing conditions in Wistar rats beginning on postnatal day (P) 21, rearing them in pairs (RP), in isolation (RI), or purchased adults rats reared at the facility (RF). We tested adult rats in the open field test, the social interaction habituation test (SI-Hab), which is a social safety learning animal model, and in the social recognition test (SRT), which is an animal model of sociability and social memory. Rats RI showed generalized increases in SI time compared to rats RP. However, there was no effect of rearing on acquisition of social safety during SI-Hab. During the SRT, rats RI exhibited a preference for a novel rat indicating robust social memory, whereas rats RP did not. Rats RF exhibited higher thigmotaxis relative to RP and RI and lower movement compared to RP in the novel open field. Numerous social and non-social behaviors were correlated with each other, and some depended on rearing condition. Based on correlation differences between RI and RP rats, RI history may be more conducive to the anxiolytic aspects of the SI-Hab protocol, which may improve the ability to deal with a perceived threat.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115481"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the neuroprotective potential of arbutin in 3-NPA induced HD-like pathology: Insights from in silico, in vitro, and in vivo models","authors":"Pooja Temgire ,&nbsp;Richmond Arthur ,&nbsp;Shubham Upadhayay ,&nbsp;Sahil Arora ,&nbsp;Gargi Kapatia ,&nbsp;Raj Kumar ,&nbsp;Uma shanker Navik ,&nbsp;Puneet Kumar","doi":"10.1016/j.bbr.2025.115475","DOIUrl":"10.1016/j.bbr.2025.115475","url":null,"abstract":"<div><div>Huntington’s disease (HD) is an inherited, hyperkinetic condition manifested by a triad of motor abnormalities, progressive cognitive impairment, and psychiatric disturbances. Oxidative stress has been implicated among other cellular processes in the pathogenesis of HD. Arbutin, a hydroquinone antioxidant, is reportedly neuroprotective in several animal models of neurodegenerative diseases. Hence, this research aimed to investigate the neuroprotective effect of arbutin against HD using <em>in silico, in vitro, and in vivo</em> experimental approaches. Schrodinger software was used for the <em>in-silico</em> studies, while SH-SY5Y cells were used for <em>in-vitro</em> studies. In the <em>in vivo</em> studies, adult Wistar rats were divided into five groups and 3-nitro propionic acid (3-NPA) (10 mg/kg/day,<em>i.p)</em> alone, and with arbutin (50 and 100 mg/kg/day,<em>i.p.</em>) was administered for 21 days. The body weight and behavioral parameters, including locomotor activity and motor coordination, were assessed on the 1st, 7th, 14th &amp; 21st days. On the 22nd day, animals were sacrificed; the striatum was harvested for biochemical, neurochemical, and histopathological assessment. <em>In silico,</em> results indicated that arbutin showed a good binding affinity for target proteins like Akt and Nrf2. Further, arbutin prevented cell death and oxidative stress in SH-SY5Y cells induced by 3-NPA. In addition, arbutin ameliorated the 3-NPA induced motor impairments, purine nucleoside imbalances (adenosine levels and its metabolites hypoxanthine, xanthine, adenine), oxidative stress, and histological alterations in the experimental animals. In conclusion, the present findings indicate that arbutin could be used as an adjuvant for the management of Huntington’s disease.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115475"},"PeriodicalIF":2.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resilience in good outcome patients with fatigue after aneurysmal subarachnoid hemorrhage","authors":"Hajar Ghafaji ,&nbsp;Tonje Haug Nordenmark ,&nbsp;Elin Western ,&nbsp;Wilhelm Sorteberg ,&nbsp;Tanja Karic ,&nbsp;Angelika Sorteberg","doi":"10.1016/j.bbr.2025.115466","DOIUrl":"10.1016/j.bbr.2025.115466","url":null,"abstract":"<div><div>Resilience is a psychological process that encompasses various facets of personality traits, behaviour, as well as coping, and it enhances the adjustment to adversities faced. Although a lot of interest has been devoted to the protective effects of resilience in handling affective disorders, little is known about the relationship between resilience and chronic fatigue, which is a common and potentially disabling sequel in survivors of aneurysmal subarachnoid hemorrhage (aSAH). Ninety-six good outcome patients with chronic post-aSAH fatigue answered the Resilience Scale for Adults (RSA) which assesses 6 distinct aspects of resilience. They also answered the Fatigue Severity Scale (FSS), Mental Fatigue Scale (MFS), Beck Depression Inventory (BDI-II), Beck’s Anxiety Inventory (BAI), and the Brief COPE. The RSA scores were related to fatigue, emotional burden and coping. The prevailing resilience factor was “Social Resources”. Patients with the highest scores for fatigue and emotional symptoms scored significantly lower for the factors “Perception of Self”, “Perception of Future” and “Family Cohesion”. Patients with clinically significant depression scored low across most RSA factors, with the weakest factors being “Perception of Self” and “Perception of Future”. Resilience factors were positively associated with adaptive problem focused coping strategies, and in particular with the emotional coping strategy “Acceptance”, whereas they correlated negatively with maladaptive avoidant coping. strategies. There is a close interaction between high resilience, adaptive coping strategies and lower burden of chronic fatigue and emotional symptoms.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115466"},"PeriodicalIF":2.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression in chronic kidney disease: Particularities, specific mechanisms and therapeutic considerations, a narrative review","authors":"Antoine Lefrère ,&nbsp;Stéphane Burtey ,&nbsp;Stanislas Bobot ,&nbsp;Raoul Belzeaux ,&nbsp;Mickaël Bobot","doi":"10.1016/j.bbr.2025.115467","DOIUrl":"10.1016/j.bbr.2025.115467","url":null,"abstract":"<div><h3>Introduction</h3><div>Depression is highly prevalent during chronic kidney disease (CKD) with studies suggesting prevalence rates ranging from approximately one-quarter to half of CKD patients. CKD and depression have a bidirectional relationship, each disorder aggravating the other, leading to more complex and challenging patient management. Depression during CKD is multifactorial and is associated with increased risk of adverse events and hospitalization.</div></div><div><h3>Methods</h3><div>We conducted a narrative review of experimental and observational studies in animals and humans, as well as meta-analyses, to explore specific mechanisms of depression in CKD and its treatment.</div></div><div><h3>Results</h3><div>In depression the gut-brain axis is central. CKD leads to an accumulation of gut-derived uremic toxins. One key factor is the accumulation of tryptophan-derived uremic toxins like kynurenines or indoxyl sulfate, whose serum concentration increases progressively with the stage of CKD (up to 100-fold in stage 5), and which plays an important role in depression mechanisms, by activating aryl hydrocarbon receptor, decreasing brain concentrations of serotonin by approximately 40 %, increasing brain inflammation, via activation of microglia and astrocytes and release of TNFα, IL-6 and NO. Randomized controlled studies found limited or no benefits of antidepressants for depressive symptoms in CKD and hemodialysis patients.</div></div><div><h3>Conclusion</h3><div>Chronic inflammation, in relation to uremic toxin accumulation during CKD, seems to be a complex but important mechanism for treatment resistance in depression. Future research should consider inhibitors of uremic toxins inhibitors and anti-inflammatory molecules as potential therapeutic agents, to improve the prognosis of depression in CKD patients.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115467"},"PeriodicalIF":2.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}