Behavioural Brain Research最新文献

{"title":"Context-dependency of vicarious extinction learning","authors":"Armin Zlomuzica ,&nbsp;Friederike Raeder ,&nbsp;Sarah Reher ,&nbsp;Miriam Lange ,&nbsp;Ekrem Dere","doi":"10.1016/j.bbr.2025.115461","DOIUrl":"10.1016/j.bbr.2025.115461","url":null,"abstract":"<div><h3>Background and objectives</h3><div>It is well documented that the fear of specific stimuli and situations can be acquired through the social observation of the actions of another person. In contrast, it is still a matter of debate, whether processes related to fear attenuation, extinction, and extinction-retrieval can equally be achieved through social observation after de novo fear conditioning.</div></div><div><h3>Methods</h3><div>Here, we used a differential fear conditioning procedure and investigated whether the variation of the context of video-based vicarious extinction learning (VEL) will affect subsequent extinction learning and extinction-retrieval. Conditioned fear acquisition, extinction, and extinction-retrieval was measured using psychophysiological (skin conductance responses) and subjective measures (CS-UCS contingency ratings and CS-valence ratings).</div></div><div><h3>Results</h3><div>Participants showed enhanced fear extinction learning after VEL as compared to controls. VEL improved extinction learning relative to controls but appeared to be highly context-dependent. The beneficial effect of VEL on subsequent extinction learning was abolished when the context in which the model was performing in the video was different from the context in which the observer performed all stages of the experiment.</div></div><div><h3>Limitations</h3><div>Data were obtained in a non-clinical sample which does not permit the extrapolation of findings to clinical populations.</div></div><div><h3>Conclusion</h3><div>Our results suggests that safety information derived from VEL promotes fear extinction when model and observer perform the experiment in the same context. Given that fear extinction is considered as an experimental proxy of exposure therapy, our findings might be instructive for the development of novel clinical interventions to promote exposure treatment efficacy.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115461"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073748","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 role of the intraparietal sulcus in numeracy: A review of parietal lesion cases","authors":"Erin Duricy ,&nbsp;Corrine Durisko ,&nbsp;Julie A. Fiez","doi":"10.1016/j.bbr.2025.115453","DOIUrl":"10.1016/j.bbr.2025.115453","url":null,"abstract":"<div><div>Prominent theories of numeracy link the intraparietal sulcus (IPS) to approximate representations of quantity that undergird basic math abilities. The goal of this review is to better understand the neural basis of mathematical cognition through the lens of acalculia, by identifying numeracy-focused single case studies of patients with parietal lesions and testing for causal relationships between numeracy impairments and the locus of parietal damage. A systematic literature review identified 27 single case studies with left parietal lesions and categorized administered tasks across four numeracy domains: Approximation, Calculation, Ordinality/Cardinality, and Transcoding. We compared published lesion images by drawing a sphere at the inferred center-of-mass and assigning each case to an anatomical group (IPS or Other Parietal damage) based on overlap with left IPS and original anatomical description. We performed Fisher’s Exact Test to compare behavioral performance on each numeracy domain between the two groups. As an exploratory follow-up, we used Activation Likelihood Estimation (ALE) to identify sites of damage within parietal cortex preferentially associated with impairments in each domain. We found that Approximation impairments were significantly more frequent in the IPS group (p = .003). The exploratory ALE analysis revealed that only Approximation impairment cases significantly overlapped with the IPS, while impairments in other domains were localized to different regions of the parietal lobe. Based on the pattern of impairments shown across these cases, we conclude that damage to the left IPS is linked to impairments in approximation ability specifically. Our findings support theoretical claims linking IPS to magnitude representation, but do not provide evidence that IPS critically underpins performance across all numeracy tasks. Instead, our findings are more compatible with models of dissociable circuits of numerical processing within the parietal lobe.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115453"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073143","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":"Standardized extract of Ginkgo biloba induced memory consolidation in female mice with hypofunction of vesicular acetylcholine transporter","authors":"Beatriz G. Muratori ,&nbsp;Irina Emanuela T. da Veiga ,&nbsp;Gleiciene N. Medeiros ,&nbsp;Sofia M.S. E. Silva ,&nbsp;Andressa G. Soliani ,&nbsp;Carla Máximo Prado ,&nbsp;Suzete M. Cerutti","doi":"10.1016/j.bbr.2025.115455","DOIUrl":"10.1016/j.bbr.2025.115455","url":null,"abstract":"<div><div>Basal forebrain cholinergic neurons are pivotal for cholinergic signaling in the neocortex and hippocampal formation, crucially implicated in neurodegenerative diseases like late-onset Alzheimer's disease (LOAD), recognition memory impairments, and decision-making. The acetylcholine transporter (VAChT) is essential for loading acetylcholine into synaptic vesicles. Building on our previous findings showing that <em>Ginkgo biloba</em> extract (EGb) preserves recognition memory, we hypothesized EGb would enhance memory in female mice with varying VAChT reductions. We also explored whether reduced cholinergic signaling induces anxiety-like behavior and whether EGb could alleviate such symptoms. Three-month-old female mice with severe VAChT reduction (knockdown homozygotes; VAChT KD^HOM), moderate reduction (heterozygotes; VAChT KD^HET), and wild-type (WT) mice received the vehicle, 5 mg/kg Donepezil, or EGb at doses of 250, 500, and 1000 mg/kg for 30 days. Memory assessments included aversive tasks like discriminative avoidance memory and non-aversive tasks like object recognition and location memory. We assessed VAChT protein expression in the hippocampal formation (HF) using Western blotting and quantified VAChT-immunopositive cells (IR⁺) in specific HF subfields (dCA1, dCA3, dDG) using immunohistochemistry. Chronic EGb treatment significantly improved long-term memory in female VAChT KD^HOM mice in object recognition and locations memories in a dose-dependent manner, unlike Donepezil. Enhanced memory was correlated with an increase in VAChT-IR⁺ cells in the dCA1 of VAChT KD^HOM mice. Additionally, EGb reduced VAChT-IR⁺ cells in the dDG of VAChT KD^HET mice, which was associated with decreased anxiety-like behavior. These findings suggest that EGb effectively mitigates deficits caused by cholinergic deficiency in hippocampal-dependent memory consolidation, thereby improving our understanding of its role in modulating long-term memory and hippocampal plasticity.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115455"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073142","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":"Update on autoimmune dementia and its precursors","authors":"Niels Hansen","doi":"10.1016/j.bbr.2025.115460","DOIUrl":"10.1016/j.bbr.2025.115460","url":null,"abstract":"<div><div>Autoimmune dementia is a new disease entity increasingly coming into focus, and novel neural antibodies associated with dementia and its precursors have been described. However, the significance of these novel and emerging autoantibodies in conjunction with cognitive disorders is unclear. Antibodies such as Leucin-Rich, Glioma Inactivated 1 (LGI1) and N-Methyl-D-Aspartate Receptor (NMDAR) are already known to be pathogenic by triggering anomalies in synaptic plasticity and learning processes in animal models after having been transferred from humans to animals. In this review we describe various pathogenic mechanisms of antibodies such as complement dependent cytotoxicity, the internalization of membrane receptors, antagonistic effects, and alterations in vesicle endocytosis at the synaptic level. We also discuss established autoantibodies such as membrane-surface and intracellular antibodies in connection with cognitive disorders, as well as autoantibodies associated with neurodegenerative dementia, and autoimmune encephalitis with primary dementia syndrome. Test methods and the response to immunotherapy are also briefly explained. This overview provides a differentiated presentation of a heterogeneous dementia entity with its precursors, which requires more research to develop a differentiated treatment guideline.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115460"},"PeriodicalIF":2.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073448","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":"Comparative analysis of sleep deprivation models: Impacts on sleep architecture, emotional state, cognitive function, and biochemical indicators in male rats","authors":"Yiyang Zhao ,&nbsp;Runchen Fang ,&nbsp;Hongsheng Bian ,&nbsp;Kexing Zhang ,&nbsp;Shuang Yu ,&nbsp;Yanyan Wang ,&nbsp;Lili Huang","doi":"10.1016/j.bbr.2025.115451","DOIUrl":"10.1016/j.bbr.2025.115451","url":null,"abstract":"<div><div>Sleep deprivation significantly affects both physiological and psychological health, with various experimental models used to study these impacts. This study compares three sleep deprivation models—Modified Multiple Platform Method (MMPM), treadmill method, and p-chlorophenylalanine (PCPA) method—on key physiological, cognitive, and emotional parameters in male Sprague-Dawley rats. The rats were subjected to 72 hours of sleep deprivation using these methods, followed by behavioral, cognitive, physiological, and biochemical assessments. Results indicated that the treadmill and PCPA methods led to significant reductions in both NREM and REM sleep (<em>P</em> &lt; 0.05), with the PCPA method showing the most severe emotional effects, including heightened anxiety and depressive behaviors (<em>P</em> &lt; 0.001). Cognitive impairments were most pronounced in the MMPM and treadmill groups (<em>P</em> &lt; 0.01). All sleep deprivation models showed signs of autonomic nervous system dysfunction, as reflected by elevated LF/HF ratios in heart rate variability assessments (<em>P</em> &lt; 0.05). Neurochemical analysis revealed reductions in hypothalamic 5-HT, Glu, and GABA levels, with the MMPM and treadmill methods causing more pronounced decreases (<em>P</em> &lt; 0.05). Additionally, IL-2 levels significantly decreased while TNF-α levels increased in sleep-deprived rats compared to controls (<em>P</em> &lt; 0.05). These findings highlight the distinct physiological, emotional, and cognitive impacts of different sleep deprivation models, providing a basis for model selection in future studies.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115451"},"PeriodicalIF":2.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073486","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":"The cerebellar connectome","authors":"Jackson Tyler Boonstra","doi":"10.1016/j.bbr.2025.115457","DOIUrl":"10.1016/j.bbr.2025.115457","url":null,"abstract":"<div><div>The cerebellum, once primarily associated with motor functions, has emerged as a critical component in higher cognitive processes and emotional regulation. This paradigm shift frames the cerebellum as an essential focal point for elucidating sophisticated functional brain circuitry. Network neuroscience often maintains a cortical-centric viewpoint, potentially overlooking the significant contributions of the cerebellum in connectome organization. Enhanced recognition and integration of cerebellar aspects in connectomic analyses hold significant potential for elucidating cerebellar circuitry within comprehensive brain networks and in neuropsychiatric conditions where cerebellar involvement is evident. This review explores the intricate anatomy, connectivity, and functional organization of the cerebellum within the broader context of large-scale brain networks. Cerebellar-specific networks are examined, emphasizing their role in supporting diverse cognitive functions via the cerebellum's hierarchical functional organization. The clinical significance of cerebellar connectomics is then addressed, highlighting the interplay between cerebellar circuitry and neurological and psychiatric conditions. The paper concludes by considering neurostimulation treatments and future directions in the field. This comprehensive review underscores the cerebellum's integral role in the human connectome.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115457"},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063277","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":"Serum KNG and FVIII may serve as potential biomarkers for depression","authors":"Guoqing Gao ,&nbsp;Hailong Ge ,&nbsp;Bei Rong ,&nbsp;Limin Sun ,&nbsp;Lujia Si ,&nbsp;Junjie Huang ,&nbsp;Chen Li ,&nbsp;Junhua Huang ,&nbsp;Lan Wu ,&nbsp;Haomian Zhao ,&nbsp;Mingzhe Zhou ,&nbsp;Yinping Xie ,&nbsp;Ling Xiao ,&nbsp;Gaohua Wang","doi":"10.1016/j.bbr.2025.115454","DOIUrl":"10.1016/j.bbr.2025.115454","url":null,"abstract":"<div><h3>Background</h3><div>The global burden of major depressive disorder (MDD) is rising, with current diagnostic methods hindered by significant subjectivity and low inter-rater reliability. Several studies have implied underlying link between coagulation-related proteins, such as kininogen (KNG) and coagulation factor VIII (FVIII), and depressive symptoms, offering new insights into the exploration of depression biomarkers. This study aims to elucidate the roles of KNG and FVIII in depression, potentially providing a foundational basis for biomarker research in this field.</div></div><div><h3>Methods</h3><div>A three-part experiment was conducted: (1) we measured serum levels of KNG and FVIII in the chronic unpredictable mild stress (CUMS) model; (2) KNG adeno-associated-virus overexpression (KNG-AAV-OE) model was constructed to further investigate the roles of KNG and FVIII. Meanwhile, quantity PCR, western blotting and immunofluorescence staining detected the KNG-FVIII pathway. (3) Peripheral blood samples were gathered from healthy control (HC, N = 21), as well as first-episode drug-naive patients with MDD (FEDN-MDD, N = 21), to further confirm the association between KNG, FVIII and depression.</div></div><div><h3>Results</h3><div>Firstly, serum KNG and FVIII levels were significantly elevated in the CUMS model. Then, the rats exhibited pronounced depressive-like behaviors in the KNG-AAV-OE model, with corresponding increases in serum KNG and FVIII. Lastly, clinical data showed increased KNG and FVIII levels in FEDN-MDD compared to HC. Furthermore, KNG and FVIII levels exhibited a strong positive correlation with the scores of the 24-item Hamilton Depression Scale and the 14-item Hamilton Anxiety Scale.</div></div><div><h3>Conclusion</h3><div>To sum up, this study highlights critical roles of serum KNG and FVIII in depression and the KNG-AAV-OE may lead the augment of FVIII in serum. Consequently, our research may offer new evidence and foundation for depression biomarkers research in the future.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115454"},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063272","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":"Permanent tactile sensory loss reduces neuronal activity in the amygdala and ventral hippocampus and alters anxiety-like behaviors","authors":"Nereida Ibarra-Castaneda ,&nbsp;Veronica Lopez-Virgen ,&nbsp;Norma Moy-Lopez ,&nbsp;Oscar Gonzalez-Perez","doi":"10.1016/j.bbr.2025.115456","DOIUrl":"10.1016/j.bbr.2025.115456","url":null,"abstract":"<div><div>Tactile information from the whiskers (vibrissae) travels through the somatosensory cortex to the entorhinal cortex and the hippocampus, influencing development and psychological well-being. The lack of whiskers affects cognitive functions, spatial memory, neuronal firing, spatial mapping, and neurogenesis in the dorsal hippocampus. Recent studies underline the importance of tactile experiences in emotional health, noting that while tactile stimuli modulate the dorsal hippocampus, the effects of tactile deprivation on anxiety-like behaviors and neural activity in regions like the ventral hippocampus and amygdala are less understood. This study aims to investigate the impact of permanent tactile deprivation on modifying anxiety-like behaviors and c-Fos expression (a marker of neuronal activity) in the dorsolateral and central nucleus of the amygdala and the ventral hippocampus, two regions involved in emotional memory and anxiety. We sectioned the infraorbital nerve, responsible for transmitting whisker information, in CD1 mice to examine how tactile deprivation modifies the behavioral activity in the Elevated Plus Maze and Open-Field Test. Our data revealed a reduction in anxiety-related behaviors post-deprivation, which was linked to a significant decrease in c-Fos expression in the barrel cortex, as well as ventral hippocampus (CA1, dentate gyrus) and dorsolateral, central nucleus of the amygdala, suggesting impaired processing in emotional-regulator brain regions. In conclusion, tactile inputs reduce neuronal activity regulators in brain regions related to emotional regulation, which may trigger possible failures in risk perception or self-protective behaviors associated with the lack of appropriate anxiety responses.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115456"},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063207","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":"Exploratory structural neuroimaging examination of impulsivity in severe alcohol use disorder: Persistent implication of the ventral striatum","authors":"Nicolas Cabe ,&nbsp;Shailendra Segobin ,&nbsp;Céline Boudehent ,&nbsp;Alice Laniepce ,&nbsp;Anne Lise Pitel","doi":"10.1016/j.bbr.2025.115452","DOIUrl":"10.1016/j.bbr.2025.115452","url":null,"abstract":"<div><h3>Background</h3><div>While Alcohol Use Disorder (AUD) is frequently associated with impulsivity, its structural brain substrates are still poorly defined. The triadic model of addiction postulates that impulsive behavior is regulated by an amygdalo-striatal impulsive subcomponent, a prefrontal and cerebellar reflective subcomponent, and an insular regulatory subcomponent. The objective of this study was thus to examine the relationships between self-evaluated impulsivity and structural brain abnormalities in patients with severe AUD (sAUD) using the triadic model as a theoretical framework.</div></div><div><h3>Methods</h3><div>Twenty-two inpatients with sAUD and 17 Healthy Controls (HC) completed two impulsivity scales: the Barratt Impulsiveness Scale-11 (BIS-11), and the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency Impulsive Behavior Scale (UPPS). They also underwent an anatomical MRI. The brain volumes of the regions described as involved in the three subcomponents of the triadic model were extracted.</div></div><div><h3>Results</h3><div>The two groups did not significantly differ on self-reported impulsivity measures. However, the volumes of the caudate nuclei, executive cerebellum and insula were smaller in sAUD than in HC. In the sAUD group there were significant positive correlations between certain impulsivity measures and gray matter volume of the nucleus accumbens.</div></div><div><h3>Conclusions</h3><div>In sAUD, self-evaluated impulsivity specifically relates to the integrity of the ventral striatum that belongs to the impulsive subcomponent of the triadic neurocognitive model of addiction. It is not related to the integrity or deterioration of the brain regions that underlie the reflexive or regulatory sub-component. Although these results have methodological limitations, they are consistent with the impulsive/compulsive model of addiction and confirms the persistence of the relationship between impulsivity and ventral striatum in sAUD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115452"},"PeriodicalIF":2.6,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057846","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":"Gut microbiome and serum metabolites in neuropathic pain: The PPARα perspective","authors":"Yu-Ying Zhao ,&nbsp;Zi-Jun Wu ,&nbsp;Yue Du ,&nbsp;Qing-qing Han ,&nbsp;Yuan-yuan Bai ,&nbsp;Bin Liu ,&nbsp;Jing Li","doi":"10.1016/j.bbr.2025.115442","DOIUrl":"10.1016/j.bbr.2025.115442","url":null,"abstract":"<div><div>Neuropathic pain (NP) is a chronic disease state centred on neuroinflammation with a high prevalence and limited effective treatment options. Peroxisome proliferator-activated receptor α (PPARα) has emerged as a promising target for NP management due to its anti-inflammatory properties. Recent evidence highlights the critical role of the gut microbiome and its metabolites in NP pathogenesis. This study aimed to investigate whether PPARα modulates the development and alleviation of NP by influencing gut microbial communities and serum metabolites. 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS/MS) untargeted metabolomics analyses performed 14 days after the establishment of a chronic constriction injury (CCI) pain model in C57BL/6 J mice showed significant changes in gut microbial and metabolite levels in CCI mice. Intraperitoneal injection of the PPARα agonist GW7647 (5 mg/kg) significantly attenuated mechanical allodynia and thermal hyperalgesia in CCI mice, whereas injection of the PPARα antagonist GW6471 (20 mg/kg) produced the opposite effect. Immunofluorescence analysis revealed that GW7647 effectively suppressed microglial activation. Additionally, PPARα agonist and antagonist treatments markedly altered the composition and abundance of intestinal microbial communities in CCI mice. Further serum LC-MS/MS analysis identified 258 potential serum metabolic biomarkers, many of which correlated with changes in gut microbial composition. These findings demonstrate that PPARα influences serum metabolite profiles by modulating gut microbiota composition, which subsequently affects NP progression. This study provides novel insights into the mechanisms underlying NP and suggests potential therapeutic avenues targeting PPARα and gut microbiota.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115442"},"PeriodicalIF":2.6,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045509","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}