Behavioural Brain Research最新文献

{"title":"Transcriptomic integration nominates FOXN2 as a candidate schizophrenia risk gene","authors":"Ling Yu , Jian Chen , Shanshan Du , Qing Long , Zeyi Guo , Yilin Liu , Fuyi Qin , Mengxue Wang , Raoxiang Luo , Yunqiao Zhang , Yong Zeng , Zhaowei Teng","doi":"10.1016/j.bbr.2026.116068","DOIUrl":"10.1016/j.bbr.2026.116068","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia (SCZ) is increasingly recognized as a complex, systemic disorder involving interactions between the central nervous system and peripheral biological processes. Growing evidence implicates dysregulation of the gut–brain axis in SCZ pathophysiology; however, the genetic mechanisms linking schizophrenia susceptibility to gut-related biological pathways remain poorly understood, particularly with respect to causal gene prioritization across tissues.</div></div><div><h3>Methods</h3><div>To address this gap, we conducted a cross-tissue transcriptome-wide association study (TWAS) using FUSION across five tissues relevant to brain–gut interactions, including the hippocampus, frontal cortex (BA9), transverse colon, sigmoid colon, and whole blood. Candidate genes were further prioritized using MAGMA gene-based analysis based on schizophrenia genome-wide association study (GWAS) summary statistics from the Psychiatric Genomics Consortium and the IEU Open GWAS project. Integrative analyses combining summary-data–based Mendelian randomization (SMR) and Bayesian colocalization (PP.H4 > 0.75) were applied to refine candidate gene selection. Expression of the top candidate gene was examined by RT-qPCR in peripheral blood samples from 19 patients with SCZ and 21 healthy controls. Finally, two-sample Mendelian randomization (MR) analyses were performed to explore potential associations between the prioritized gene and 205 gut microbial metabolic pathways.</div></div><div><h3>Results</h3><div>Cross-tissue integration of TWAS, MAGMA, and SMR identified five convergent schizophrenia susceptibility genes: <em>TVP23B, NSUN2, RPL12, FOXN2</em>, and <em>THAP5</em>. Bayesian colocalization analysis highlighted <em>FOXN2</em> as the most robust candidate (PP.H4 =0.995). RT-qPCR analysis demonstrated significantly lower <em>FOXN2</em> expression in peripheral blood from patients with schizophrenia compared with healthy controls (mean ± SD: 0.72 ± 0.64 vs.1.13 ± 0.42; <em>t</em> = 2.34, <em>P</em> = 0.02). In two-sample MR analyses, genetically proxied <em>FOXN2</em> expression was modestly but significantly associated with 10 gut microbial metabolic pathways after false discovery rate correction, suggesting potential links between schizophrenia risk genes and gut microbial metabolic processes.</div></div><div><h3>Limitations</h3><div>This study relies on cis-eQTL–based transcriptomic integration and assumes a single causal variant in colocalization analyses. The number of available MR instruments was limited, and the clinical validation sample size was modest, with residual confounding not fully excluded. In addition, the GWAS and eQTL datasets were predominantly derived from populations of European ancestry, which may limit generalizability. The observed associations between <em>FOXN2</em> and gut microbial metabolic pathways should therefore be considered exploratory and require further functional validation.</div></div><div><","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116068"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091742","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":"Neural mechanisms of enhanced emotional experience during live sports viewing: Multimodal evidence from fNIRS and EEG","authors":"Jiajia Yu ,&nbsp;Le Liu ,&nbsp;Yang Liu ,&nbsp;Ying Hou","doi":"10.1016/j.bbr.2026.116086","DOIUrl":"10.1016/j.bbr.2026.116086","url":null,"abstract":"<div><div>The real-time nature and outcome uncertainty of live sports viewing can shape viewer’ emotional experiences through suspense, yet the neural mechanisms remain unclear. This study employed simultaneous fNIRS–EEG recording, combined with behavioral measures, to systematically examine suspense-driven emotional arousal and its neural basis during live versus replayed table tennis matches. Behaviorally, participants reported significantly stronger suspense, higher emotional arousal, and greater pleasure in the live condition compared to the replay condition. Neuroimaging results showed that live viewing selectively activated the left frontal cortex and increased β-band oscillatory activity in both the left frontal and left parietal regions. The simultaneous fNIRS–EEG analysis further revealed a significant increase in neurovascular coupling efficiency within the left frontal cortex during live viewing, suggesting that suspense-related cognitive load facilitates neural-metabolic coordination. Mediation analysis demonstrated that left frontal activation partially mediated the relationship between suspense perception and emotional arousal, whereas left frontal β-band oscillatory activity did not show a significant mediating effect in the pathway from suspense perception to emotional arousal. Together, these multimodal findings reveal a left frontal cognitive–emotional integration mechanism through which live sports viewing, driven by suspense, enhances emotional experience. The results provide novel empirical evidence for the neural pathways by which suspense in non-fictional media modulates emotional processing.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116086"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172404","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":"Male paternal exposure to predatory risk during adolescence alters offspring antipredator behavior and basal HPA axis activity in Brandt’s voles","authors":"Ping Wang ,&nbsp;Taoxiu Zhou ,&nbsp;Yinyue Gu,&nbsp;Xinyi Lan,&nbsp;Wanhong Wei,&nbsp;Ruiyong Wu","doi":"10.1016/j.bbr.2026.116073","DOIUrl":"10.1016/j.bbr.2026.116073","url":null,"abstract":"<div><div>Adolescent stress not only exerts enduring effects on individual behavior and physiology, but also shapes offspring phenotypes through mechanisms of transgenerational inheritance. However, the transgenerational effects of predation risk, an important ecological factor, remain poorly characterized in wild, social rodents. Using male Brandt's voles (<em>Lasiopodomys brandtii</em>) as a model, this study systematically investigated the transgenerational effect of adolescent exposure to cat urine, rabbit urine (as a non-predator stimulus), and distilled water (as a control) for 60 min daily over 18 consecutive days on the behavioral and physiological traits of future offspring. Our data showed that while male paternal adolescent cat odor (CO) exposure did not significantly alter overall parental investment by either parent, it induced significant phenotypic changes in offspring. These included an increased female ratio at weaning and reduced post-weaning weight gain. Furthermore, adolescent offspring exhibited decreased locomotor activity in the open field test, while adult offspring displayed heightened vigilant rearing and reduced head-out behavior when confronted with CO exposure. These behavioral and developmental alterations were accompanied by elevated serum levels of adrenocorticotropic hormone and corticosterone, suggesting enhanced basal activity of the hypothalamic-pituitary-adrenal axis. These findings demonstrate that male paternal experience with predation risk during adolescence can transgenerationally regulate the sex ratio, growth and development, stress response, and antipredator strategies of future offspring, independent of alterations in parental investment in wild, social rodents. This study elucidates the unique role of the paternal lineage in the transgenerational inheritance of early adversity and provides further experimental evidence for understanding how environmental stress drives adaptive phenotypic transmission across generations.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116073"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103648","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":"Fine motor function deficits in the 5xFAD mouse model of Alzheimer’s disease","authors":"Stylianos Valiantis ,&nbsp;Nikolas Perentos ,&nbsp;Andreas M. Koupparis ,&nbsp;Avgis Hadjipapas ,&nbsp;Savvas S. Papacostas ,&nbsp;Ioanna Kousiappa","doi":"10.1016/j.bbr.2026.116097","DOIUrl":"10.1016/j.bbr.2026.116097","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) involves not only progressive memory and cognition deficits but also motor impairments, including disturbed balance and activity levels and gait dysfunction. We examined age-related changes in fine motor skills of an Alzheimer’s mouse model, the transgenic 5xFAD, from 3 to 9 months of age (3 M, 9 M), using a battery of behavioral tests including the rotarod for motor coordination and balance, balance beam test for fine motor precision and coordination, and single-pellet reaching test for forelimb dexterity. Rotarod test showed that 9 M 5xFAD mice displayed mild motor coordination deficits, spending less time on the rod and falling at lower speeds than 9 M WT mice. In the balance beam test, 9 M 5xFAD mice exhibited significantly slower traversal times compared to other groups and demonstrated frequent foot slips and dragging behavior with more pronounced effects on the narrower beam. The single-pellet reaching test revealed impaired fine limb movements in 9 M 5xFAD mice, with reduced success rates and slower speed than the other groups. This study showed that 9 M 5xFAD mice exhibited the most impaired performance at each assay in an age-dependent manner, suggesting that the accumulation of the underlying AD-related pathology affects motor function, extending even to fine motor skills.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116097"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155914","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":"Gestational hyperglycemia and autism spectrum disorder: Mechanistic pathways and emerging preventive strategies","authors":"Diksha Wadhwani,&nbsp;Snehal S. Patel","doi":"10.1016/j.bbr.2026.116099","DOIUrl":"10.1016/j.bbr.2026.116099","url":null,"abstract":"<div><div>Autism spectrum disorder is a neurodevelopmental disorder characterised by deficits in social communication, restricted interests, and repetitive behaviours. The severity and presentation of symptoms vary greatly among autistic individuals. The etiology of autism is multifactorial, including metabolic, environmental, and genetic factors. Emerging evidence suggests that the maternal metabolic environment, especially gestational diabetes mellitus, has a major impact on fetal neurodevelopment and the subsequent risk of autism spectrum disorder. Epidemiological studies have found that children born to mothers with gestational diabetes mellitus are much more likely to be diagnosed with autism, especially if GDM is identified before 26 weeks of pregnancy. The mechanistic pathways that link maternal hyperglycemia to autism are explored in this review. These include epigenetic suppression of SOD2, impaired neuronal migration through disrupted reelin signalling, elevated oxidative stress from advanced glycation end products, gut dysbiosis and many more, caused by GDM. The cumulative effect of the above factors involves disturbances in the intrauterine environment, which results in abnormal synaptic formation, neuroinflammation, and mitochondrial dysfunction in the developing fetal brain. This review also examines the new therapeutic strategies that can target these pathways, such as RORα agonist, SGLT-2 and DPP4 inhibitors, antioxidants and gut microbiota modification through various dietary interventions and supplementation to support the growth of beneficial microbiota. Thus, early detection and treatment of maternal metabolic disorders during pregnancy may be a promising way to lower the risk of autism in infants and enhance the neurodevelopmental outcomes.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116099"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172451","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":"Age-related impairments in scene-based mnemonic pattern separation","authors":"Mingyue Zhang ,&nbsp;Qiuxuan Yu ,&nbsp;Tingting Wu ,&nbsp;Yin Jiao Li ,&nbsp;Wenrong Wen ,&nbsp;Jiahui Deng","doi":"10.1016/j.bbr.2026.116106","DOIUrl":"10.1016/j.bbr.2026.116106","url":null,"abstract":"<div><div>Pattern separation refers to the neural process by which overlapping inputs are transformed into distinct representations, enabling discrimination of similar experiences. This mechanism, central to episodic memory, critically depends on hippocampal integrity, which is vulnerable to age-related atrophy. The present study examined whether pattern separation is significantly reduced in older adults. We recruited healthy younger (n = 20) and older (n = 20) participants who completed a scene-based pattern separation task requiring classification of images as old, foil, or lure. Images varied in visual completeness to simulate degraded sensory input. Behavioral analyses revealed that older adults showed markedly lower overall accuracy than younger adults. They also exhibited a substantially reduced lure discrimination index and lower corrected recognition scores. Furthermore, older adults responded significantly slower. Collectively, our findings demonstrate robust age-related reductions in memory discrimination and recognition that are consistently observed across levels of perceptual degradation, in line with the vulnerability of hippocampal-dependent memory processes in aging. This research builds upon previous studies by using a scene-based MST with parametric image occlusion, offering a nuanced behavioral framework for assessing cognitive decline and memory deficits in older persons.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116106"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172454","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":"Polygenic modulations of decoy and compromise effects by dopaminergic and serotonergic systems","authors":"Yao Xiao ,&nbsp;Min Yang ,&nbsp;Yuling Huang ,&nbsp;Han Li ,&nbsp;Na Zhao ,&nbsp;Chenjin Qiao ,&nbsp;Pingyuan Gong","doi":"10.1016/j.bbr.2026.116072","DOIUrl":"10.1016/j.bbr.2026.116072","url":null,"abstract":"<div><div>Decoy effect and compromise effect are context-dependent choice biases in which adding an option shift preference without changing the original alternatives. The decoy effect increases a preference for a target by introducing an inferior comparison, whereas the compromise effect reflects a tendency to choose intermediate options. Given the established roles of dopaminergic and serotonergic pathways in reward motivation and behavioral inhibition, this study investigated whether polygenic risk scores (PRSs) within these neurotransmitter pathways could predict these two effects. Two independent samples of Chinese university students were recruited from Luoyang (Sample 1: <em>N</em> = 647) and Xi’an (Sample 2: <em>N</em> = 569), providing demographically homogeneous populations for assessing genetic contributions to decision biases. In the serotonergic system, the PRS significantly predicted compromise effect in both samples (Sample 1: <em>β</em> = 0.093, <em>p</em> = 0.017; Sample 2: <em>β</em> = 0.094, <em>p</em> = 0.026) and decoy effect in Sample 2 (<em>β</em> = 0.122, <em>p</em> = 0.003). In the dopaminergic system, the PRS only significantly predicted compromise effect in Sample 2 (<em>β</em> = 0.132, <em>p</em> = 0.002), while it significantly predicted decoy effect in both samples (Sample 1: <em>β</em> = 0.132, <em>p</em> = 0.001; Sample 2: <em>β</em> = 0.126, <em>p</em> = 0.003). Combined-sample analyses confirmed a unique contribution of dopaminergic PRS to the compromise effect and showed that the decoy effect was jointly influenced by dopaminergic and serotonergic pathways. These results show that the decoy and compromise effects arise from distinct genetic mechanisms: dopamine amplifies relative reward signals driving the decoy choices, whereas serotonin promotes safer, intermediate preferences underlying the compromise decisions.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116072"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102577","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":"Enhanced central histaminergic transmission via H1 and H2 receptor alleviates the behavioral despair, reduction in BDNF and pCREB levels in streptozotocin-induced diabetic mice","authors":"Chhatrapal Patel,&nbsp;Richa Patel,&nbsp;Vaibhav Maturkar,&nbsp;Venu Anand Das Vaishnav,&nbsp;Nishant Sudhir Jain","doi":"10.1016/j.bbr.2026.116102","DOIUrl":"10.1016/j.bbr.2026.116102","url":null,"abstract":"<div><div>The role of central histamine in diabetes induced behavioral despair is still an enigma. Therefore, the current research explored the plausible impact of the central histaminergic activity on the expression of diabetes-induced behavioral despair in mice using the tail suspension test (TST) and surose preference test (SPT) along with changes in the levels of BDNF and phosphorylated CREB (pCREB) in the whole brain, hippocampus, PFC, and amygdala. Post-streptozotocin (STZ) (200 mg/kg, i.p.) injection, on the 4^th day (called diabetic zero day), rendered the mice diabetic, while the highest blood glucose levels were observed on the 10^th day (behavioral expression and biochemical testing day) post diabetes induction. Furthermore, on the 10^th day, the diabetic mouse elicits a prolonged period of immobility on TST and reduced percentage of sucrose preference on SPT with decreased locomotion, indicating the expression of diabetes induced behavioral despair. Moreover, on the 10^th day, i.c.v. injection of histaminergic agents like histamine, its precursor, <span>L</span>-histidine, neuronal releaser of histamine (H₃ receptor antagonist), thioperamide, the H₁ receptor agonist, FMPH, or the H₂ receptor agonist, amthamine reversed the expression of diabetes induced behavioral despair in mice on TST. In addition, the TST effective doses of (i.c.v.) histamine (50 μg), <span>L</span>-histidine (2.5 μg), thioperamide (10 μg) and FMPH (6.5 μg) also restored the the sucrose consumption reduced in diabetic mice on SPT. Moreover, the ELISA test revealed that in the behaviorally depressed diabetic mice, the whole brain histamine levels were substantially diminished compared to the non-diabetic control mice. In addition, BDNF/pCREB levels was also considerably reduced in the whole brain, hippocampus, PFC, and amygdala of diabetic mice. Conversely, i.c.v. injection of histamine to diabetic mice restored the diminished BDNF/pCREB levels in the whole brain and hippocampus, while thioperamide normalized these deficits in the whole brain, hippocampus, and PFC. However, <span>L</span>-histidine treatment failed to alter reduced BDNF/pCREB levels in all brain regions of diabetic mice. Moreover, i.c.v. injection of FMPH to diabetic mice also reversed the deficit in BDNF/pCREB levels in the whole brain and hippocampus, whereas amthamine injection normalized these markers in the whole brain only. Thus, the enhanced central histaminergic transmission via H₁/H₂ receptors activation might attenuate the diabetes induced behavioral despair in mice by restoring BDNF/pCREB levels in the brain regions implicated in behavioral depression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116102"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172403","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":"Second-order conditioning of safety in male and female rats","authors":"Daniel B.K. Gabriel ,&nbsp;Kaitlin R. Crilow ,&nbsp;Susan Sangha","doi":"10.1016/j.bbr.2026.116059","DOIUrl":"10.1016/j.bbr.2026.116059","url":null,"abstract":"<div><div>Stimuli can acquire meaning and significance indirectly by being paired with other stimuli that already have known outcomes. When a stimulus has a well-established association with either aversive or rewarding consequences, other neutral stimuli can take on similar properties simply by occurring alongside it - even if the original outcome is not presented. This process is known as second-order conditioning. Relatively few studies have examined second-order conditioning of inhibitory safety memories. Here, we examined second-order conditioning of safety in adult male and female Long-Evans rats by adapting our well-established first-order safety conditioning paradigm to include novel stimuli paired with the established safety cue. Our findings demonstrate that a second-order safety cue can attenuate fear responses to a degree comparable to that of a first-order safety cue. In contrast, a novel cue that had never been paired with a safety signal failed to produce an equivalent reduction in defensive behavior during fear cue presentation, demonstrating that the reduced fear to the second-order safety cue was a product of conditioning and not external inhibition. Developing methods to generalize safety to novel stimuli that have not been explicitly conditioned for safety holds significant promise for advancing innovative strategies aimed at mitigating maladaptive fear responses.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116059"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103639","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":"Upregulation of salt-inducible kinase 2 promotes seizure susceptibility in epilepsy","authors":"Ran Sun ,&nbsp;Min Wang ,&nbsp;Xi Li ,&nbsp;Yanke Zhang","doi":"10.1016/j.bbr.2026.116104","DOIUrl":"10.1016/j.bbr.2026.116104","url":null,"abstract":"<div><div>Salt-inducible kinase 2 (SIK2) is a serine/threonine kinase implicated in several neurological disorders; however, its role in epilepsy remains unclear. In this study, temporal lobe cortex tissues from patients with temporal lobe epilepsy and control subjects, as well as tissues from epilepsy model mice, were analyzed to investigate the expression and function of SIK2. Western blotting and immunofluorescence were used to measure SIK2 expression and cellular localization in epilepsy model mice. To assess its functional relevance, the overexpression or knockdown of <em>SIK2</em> in the hippocampus was combined with a chronic PTZ kindling model to evaluate seizure susceptibility and mortality. We found that SIK2 expression was significantly increased in the cortical and hippocampal regions of epileptic mice, as well as in temporal lobe cortex of epilepsy patients, with predominant localization in neurons. Hippocampal overexpression of SIK2 decreased seizure latency, increased seizure severity, and increased mortality, whereas <em>SIK2</em> knockdown had the opposite effects. These findings indicate that SIK2 contributes to seizure susceptibility and epileptogenesis and may represent a potential molecular target for epilepsy intervention.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116104"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172453","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}