BMC Neuroscience最新文献

{"title":"Effects of repetitive mechanical tactile stimulation interventions with stationary and moving patterns on paired-pulse depression.","authors":"Hiraku Watanabe, Sho Kojima, Naofumi Otsuru, Hideaki Onishi","doi":"10.1186/s12868-025-00960-w","DOIUrl":"10.1186/s12868-025-00960-w","url":null,"abstract":"<p><strong>Background: </strong>Repetitive somatosensory stimulation (RSS) reduces paired-pulse depression (PPD), reflecting GABAergic inhibition in the primary somatosensory cortex (S1). This effect may vary by tactile stimulation pattern. Therefore, this study aimed to clarify the effects of RSS intervention with stationary and moving pattern tactile stimulation on PPD.</p><p><strong>Results: </strong>In a crossover study of 15 healthy males, RSS with a stationary pattern showed a non-significant trend toward increased PPD (corrected p = 0.088), while the moving pattern showed no effect. A strong negative correlation was found between baseline PPD and its change rate (r = - 0.837, p < 0.001), indicating that greater baseline S1 inhibition predicted a larger reduction after RSS.</p><p><strong>Conclusion: </strong>RSS effects on GABAergic inhibition in S1 depend on the tactile stimulation pattern, emphasizing the importance of tactile stimulus design in modulating somatosensory cortex activity.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"46"},"PeriodicalIF":2.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mir-199a-3p aggravates neuroinflammation in an Alzheimer's disease transgenic mouse model by promoting M1-polarization microgliaMir-199a-3p M1.","authors":"Chenyang Wang, Xiaolu Bu, Mengyao Cao, Yunyu Lian, Haocong Ling, Mo You, Junfei Yi, Xiaoya Gao, Duobin Wu, Yang Li","doi":"10.1186/s12868-025-00965-5","DOIUrl":"10.1186/s12868-025-00965-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic neuroinflammation, driven by M1-polarized microglia, is a core pathological mechanism of Alzheimer's disease (AD). Elevated expression levels of miR-199a-3p and pro-inflammatory cytokines were detected in the hippocampi of AD transgenic mice and in LPS-stimulated BV2 microglial cells. We hypothesized that miR-199a-3p exacerbates neuroinflammation by promoting M1 microglial polarization in AD progression. M1 （AD） 。 AD LPS BV2 miR-199a-3p 。 miR-199a-3p AD M1 。 OBJECTIVE: To explore the role of miR-199a-3p in AD-associated neuroinflammation. miR-199a-3p AD 。 METHODS: AD transgenic (APPswe/PSEN1dE9) mice and LPS-treated BV2 cells were used to assess miR-199a-3p effects in vivo and in vitro. Inflammatory cytokines and markers for microglial cell typing were detected. Transcriptome sequencing was performed on miR-199a-3p-modulated BV2 cells, and the sequencing data were cross-analyzed with public databases to predict miR-199a-3p-mediated pathways.AD （APPswe/PSEN1dE9） LPS BV2 miR-199a-3p 。。 miR-199a-3p BV2 ，， miR-199a-3p 。 RESULTS: Intracerebroventricular administration of miR-199a-3p agomir exacerbated amyloid deposition and impaired cognitive function in AD mice, and promoted microglial polarization toward the M1 phenotype. Conversely, treatment with miR-199a-3p antagomir attenuated AD pathology and suppressed M1 polarization. In LPS treated BV2 cells, miR-199a-3p mimics promoted M1 polarization, while inhibitors reversed this effect. Transcriptome analysis revealed that miR-199a-3p downregulated WDR76, subsequently suppressing cell cycle-associated pathways, IL-17 signaling, and FOXO pathways, resulting in an increase in the proportion of M1 type microglia. miR-199a-3p agomir AD ， M1 。， miR-199a-3p AD M1 。 LPS BV2 ，miR-199a-3p M1 ，。，miR-199a-3p WDR76，、 IL-17 FOXO ， M1 。 CONCLUSION: MiR-199a-3p aggravates neuroinflammation of AD by promoting M1-polarization microglia. These findings highlight miR-199a-3p as a potential therapeutic target for AD.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"45"},"PeriodicalIF":2.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomical and behavioral characterization of three hemiplegic animal models.","authors":"Mei Liu, Lingling Xu, Gefei Cheng, Yang Yang, Likun Yang, Yuhai Wang","doi":"10.1186/s12868-025-00961-9","DOIUrl":"10.1186/s12868-025-00961-9","url":null,"abstract":"<p><strong>Background: </strong>Hemiplegia is characterized by muscle weakness on one side of the body, often resulting from damage to the brain, spinal cord, or associated nerves. This condition commonly occurs due to strokes, traumatic brain injuries (TBI), or spinal cord injuries (SCI), which can damage corticospinal neurons (CSNs) and the corticospinal tract (CST). However, there is still a notable lack of comprehensive studies that systematically characterize the anatomical and behavioral aspects of these hemiplegic animal models.</p><p><strong>Objective: </strong>This study aimed to validate and compare existing models of TBI, stroke, and SCI in order to identify the most suitable preclinical hemiplegia models for future research.</p><p><strong>Method: </strong>Using viral-based retrograde tracing, we first mapped the cortical distribution of CSNs responsible for hindlimb movement. Anterograde and retrograde viral tracing techniques were then employed to label and evaluate the damage to CSNs and the CST in three models: photothrombotic stroke, Feeney's weight-drop TBI, and T10 hemi-section SCI. We also conducted behavioral tests to assess spontaneous motor function recovery, including open field and rotarod tests for gross motor function, as well as beam walking and irregular ladder walking tasks for assessing skilled motor function.</p><p><strong>Results: </strong>Our findings revealed that the CSNs controlling hindlimb movement are concentrated in the hindlimb region of the primary somatosensory cortex (S1HL). In the TBI and stroke models, there was complete destruction of ipsilateral CSNs in the S1HL and loss of CST fibers governing hindlimb movement. In the SCI model, ipsilateral CST fibers below T10 were also lost. After 8 weeks post-injury, all three groups of hemiplegic mice showed improvements in motor function, with gross motor function returning to normal levels; however, the recovery of skilled motor function was only modest. Notably, the degree of improvement in fine motor skills varied among the hemiplegia models, with mice subjected to brain injury (stroke and TBI) demonstrating significantly greater recovery in fine motor skills compared to those with SCI.</p><p><strong>Conclusion: </strong>We confirmed and validated previous hemiplegia models by damaging CSNs or CST controlling hindlimb movement. Post-injury, gross motor function gradually returned to normal levels across all groups, whereas recovery of skilled motor function was limited. Furthermore, there were significant differences in the recovery of skilled motor function between brain injury models and the SCI model. These hemiplegic mouse models are valuable tools for studying post-injury skilled motor functions.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"44"},"PeriodicalIF":2.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-stroke butyrate treatment shows sex-dependent microglial responses but does not improve outcomes in a mouse model of endothelin-1 sensory motor stroke.","authors":"Ashley de Witte, Juliana Montoya Sanchez, Emerson Daniele, Jingan Chen, Yibang Fan, Pranav Khatri, Daniela Lozano Casasbuenas, Angel Zhang, Kathryn G Todd, Maryam Faiz, Matthew Churchward","doi":"10.1186/s12868-025-00959-3","DOIUrl":"10.1186/s12868-025-00959-3","url":null,"abstract":"<p><strong>Background: </strong>Stroke induces gut dysbiosis and reduces microbial production of short-chain carboxylic acids (SCCAs), which negatively correlates with stroke outcomes. Previous studies have demonstrated that SCCA supplementation can improve functional recovery, with one recent study suggesting this occurs via modulation of microglial responses. However, the effects of individual SCCAs on microglial responses remain unclear, particularly across sexes and following a more clinically relevant, post-stroke treatment protocol. To address this gap, we investigated the effect of post-stroke supplementation with butyrate on stroke outcomes and microglial responses in both male and female mice over time.</p><p><strong>Results: </strong>Post-stroke butyrate treatment produced sex-specific microglial responses. In females, butyrate increased microglial ramification at chronic timepoints in vivo and enhanced IL6 release following IFNγ stimulation in vitro. These microglial changes were not observed in males. Despite the distinct microglial responses, butyrate treatment did not correlate with improved stroke outcomes in either sex, as measured by lesion volume and functional recovery.</p><p><strong>Conclusions: </strong>Our findings reveal previously unknown sex differences in microglial responses to butyrate following stroke. Despite these microglial changes in females, butyrate treatment did not improve functional outcomes in either sex, suggesting that sex-specific optimization of dosing and delivery may be needed for therapeutic efficacy.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"43"},"PeriodicalIF":2.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pharmacological and brain imaging study of human vasopressin AVP1BR receptor functional polymorphisms.","authors":"Adrián Alacreu-Crespo, Emilie Olié, Maxime Manière, Jeremy Deverdun, Emmanuelle Lebars, Maithé Corbani, Gilles Guillon, Philippe Courtet","doi":"10.1186/s12868-025-00963-7","DOIUrl":"10.1186/s12868-025-00963-7","url":null,"abstract":"<p><p>In humans, vasopressin AVP1BR receptor (hV_1B) plays key roles in hypothalamic-pituitary-adrenal (HPA) axis regulation and social behavior. Three hV_1B polymorphisms, rs35369693 (K65N), rs28632197 (R364H) and rs33990840 (G191R), have been related to psychiatric disorders with altered HPA axis function and social behavior. The aim of this study was to explore hV_1B pharmacological properties as a function of the polymorphism in transfected cells and the brain functioning in an emotional task in volunteers harboring different AVP1BR polymorphisms. Transfection rate, fluorescent imaging and inositol phosphate (IPs) accumulation were evaluated in HEK293 cells that expressed different hV_1B variants: K65/G191/R364 (wild type), G191R, K65N and/or R364H. Brain functional activity was investigated in 35 healthy men with different hV_1B variants during an fMRI implicit emotional recognition paradigm. IPs accumulation after arginine vasopressin stimulation was much reduced in cells expressing hV_1B K65N and/or R364H, and increased in cells expressing G191R. Basal IPs accumulation, transfection rate, and fluorescent binding to plasma membrane were similar for all polymorphisms. During the anger vs. neutral face visualization task, activation of motor areas, visual areas, frontal sub-gyral area, hippocampus, and putamen was higher in homozygotes for the K65/R364 haplotype than in heterozygotes. Analyses did not include participants with the G191 polymorphism because of its low frequency. Different hV_1B polymorphisms could be candidates as biomarkers of psychiatric disorders. Moreover, hV_1B may be a pharmacological target if these polymorphisms are considered.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"42"},"PeriodicalIF":2.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway.","authors":"Junjiao Zhang, Wenshu XiangWei, Fan Zhang, Huan Yi, Wei Yan, Xiao Li, Kai Gao, Yuwu Jiang","doi":"10.1186/s12868-025-00962-8","DOIUrl":"10.1186/s12868-025-00962-8","url":null,"abstract":"<p><p>Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. However, the underlying mechanisms remain unclear. This study aimed to determine the optimal concentration of Tamibarotene (Am80) for promoting neuronal differentiation and to elucidate the underlying molecular mechanisms. SH-SY5Y cells were treated with Am80 at various concentrations, and the effects on cell morphology, gene expression, cell proliferation and apoptosis assessed using immunofluorescence, Western blotting, qPCR, and RNA sequencing. Results indicated that that 1µM Am80 effectively promoted neuronal differentiation, upregulating neuronal markers and the KCNT1 gene, while downregulating tumor-related genes MYC and CXCR4. The differentially expressed genes are predominantly enriched in the PI3K-Akt signaling pathway, with upregulation of genes related to neuronal development such as NTRK2, RET, and CNR1, and downregulation of tumor-related genes including MYC and CXCR4. Inhibition of the PI3K/Akt signaling pathway using LY294002 resulted in a decreased efficacy of AM80-induced differentiation in SH-SY5Y cells, along with downregulation of neuronal marker expression. These findings suggest that Am80 can effectively promote the differentiation of SH-SY5Y cells into neurons and reduce the proliferation of neuroblastoma cells, which is related to the PI3K/AKT pathway, providing a good model for the study of nervous system diseases.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"41"},"PeriodicalIF":2.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of arabinoxylan on BDNF/TrkB/p-CREB signaling pathway in the prefrontal cortex and intestinal microbiome in post-stroke depressed rats.","authors":"Bin-Yu Bi, Lin Lin, Liu Huang, Jun Zhou, Wei-Juan Yan, Ling Huang, Jie Wang, Xue-Bin Li","doi":"10.1186/s12868-025-00964-6","DOIUrl":"10.1186/s12868-025-00964-6","url":null,"abstract":"<p><strong>Aim: </strong>To explore the effects of arabinoxylan on the BDNF/TrkB/p-CREB signaling pathway in the prefrontal cortex of post-stroke depressed rats, and to explore its neuronal protective effects through the microbial-gut-brain axis in the regulation of this pathway.</p><p><strong>Methods: </strong>The rat model of post-stroke depression (PSD) was established by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stimulation (CUMS). They were randomly divided into 5 groups (blank control, post-stroke depression, arabinoxylan, fluoxetine hydrochloride, fluoxetine hydrochloride combined arabinoxylan). The rats were treated differently for 28 days according to their grouping. Body mass, sugar and water consumption experiments and open-field experiments were used to evaluate the behavior of rats. The pathological changes were observed by H&E staining. The expression levels of amine neurotransmitters were detected by ELISA. The expression levels of BDNF mRNA and BDNF, TrkB and p-CREB were detected by RT-PCR and Western blot. The analysis of intestinal metagenomics was conducted by 16 S rDNA sequencing.</p><p><strong>Results: </strong>Compared with the post-stroke depression group, the body weight, activity and sugar water consumption rate of the arabinoxylan group were increased. The expression levels of 5-HT in the prefrontal cortex, colon and serum levels of 5-HT, DA and NE were increased. The expression levels of BDNF mRNA and BDNF, TrkB and P-CREB in the prefrontal cortex were also upregulated. The number of neurons in the prefrontal cortex increased; Colon mucosal injury and inflammatory cell infiltration decreased, the intestinal microbial diversity increased; The relative abundance of probiotics such as bifidobacterium, Christensenia, Dubosiella New York and ruminococcus increased. The relative abundance of Prevotella NK3B31 group was reduced. The level of 5-HT in the prefrontal cortex was negatively correlated with the abundance of Prevotellaceae NK3B31 group.</p><p><strong>Conclusion: </strong>Arabinoxylan improved depressive-like behavior in rats and its neuroprotective role was achieved by promoting the growth of intestinal probiotics, improving the intestinal barrier, affecting the BDNF/TrkB/p-CREB signaling pathway, and increasing the expression levels of monoamine neurotransmitters 5-HT, DA and NE.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"40"},"PeriodicalIF":2.4,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiome rewiring via fecal transplants: Uncovering therapeutic avenues in Alzheimer's disease models.","authors":"Prabhat Upadhyay, Sudhir Kumar, Anurag Tyagi, Aayush Raj Tyagi, Tarun Barbhuyan, Sarika Gupta","doi":"10.1186/s12868-025-00953-9","DOIUrl":"10.1186/s12868-025-00953-9","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence implicates the gut microbiome in Alzheimer's disease (AD) pathogenesis, yet the underlying mechanisms remain elusive. This study elucidates the bidirectional relationship between gut microbiota and AD using fecal microbiota transplantation (FMT) in a mouse model.</p><p><strong>Result: </strong>Through meticulous experimentation, we conducted reciprocal FMT between AD (5xFAD) and healthy (C57BL/6) mice to unravel the impact of gut microbiome alterations on cognitive function and neuroinflammation. FMT from 5xFAD to C57BL/6 mice induced profound memory impairment and cognitive deficits, accompanied by elevated inflammatory cytokine levels, oxidative stress markers, and systemic inflammation, as evidenced by increased plasma cytokines. Conversely, transplanting healthy microbiota into 5xFAD mice yielded remarkable behavioral improvements, including enhanced spatial memory performance in the Morris water maze, directly correlating with cognitive recovery. Our findings underscore the pivotal role of the gut microbiome in AD pathogenesis and offer a promising therapeutic avenue.</p><p><strong>Conclusion: </strong>Targeted modulation of the gut microbiome through strategies like FMT may offer potential benefits in Alzheimer's disease by influencing neuroinflammation, oxidative stress, and cognitive function. This comprehensive study provides novel insights into the gut-brain axis dynamics and paves the way for innovative microbiome-based interventions in AD management.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"39"},"PeriodicalIF":2.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish mecp2 null-mutation increases anxiety and cortisol levels but no change in adult social preference and larval chemically-induced hyperlocomotion.","authors":"Soaleha Shams, Pierre Cronell, Jenny Landin, Thomas Pietri, Adrian Ekehorn Gimdal, Petronella Kettunen, Lars Westberg","doi":"10.1186/s12868-025-00946-8","DOIUrl":"10.1186/s12868-025-00946-8","url":null,"abstract":"<p><strong>Background: </strong>Methyl CpG binding protein 2 (MECP2) is an essential global modulator of transcription and mutations in MECP2 are the most common cause of Rett syndrome, an X-linked neurodevelopmental disorder. Patients diagnosed with Rett syndrome have increased risk for epilepsy as well as problems with anxiety and social communication. Using the zebrafish mecp2^Q63X line, this study aimed to increase our understanding of the role of Mecp2 function in regulation of pharmacologically-induced hyperlocomotion, developmental social preference, and adult socialization, anxiety-related behaviour, and baseline cortisol levels. To determine responses of mecp2^-/- zebrafish to a stimulating convulsant, general locomotor activity was measured at 5 days post-fertilization (dpf) in sibling mecp2^+/+, mecp2^+/-, and mecp2^-/- fish after treatment with a GABA_A receptor antagonist pentylenetetrazol (PTZ) at varying concentrations. Responses to social stimulus were investigated in juvenile (21 dpf) and adult mecp2^-/- and mecp2^+/+ fish. Anxiety responses to a novel tank and whole-body cortisol levels were also measured in adult mecp2^-/- and control mecp2^+/+ zebrafish.</p><p><strong>Results: </strong>The behavioural tests showed that mecp2^-/- zebrafish displayed hypolocomotion at the larval stage, along with increased freezing time and thigmotaxis, and higher whole-body cortisol levels in adulthood. However, the hyper-locomotion response to PTZ at 5 dpf and social preference for visual social stimulus at 21 dpf and in adulthood were not affected by the lack of functional Mecp2.</p><p><strong>Conclusions: </strong>Functional Mecp2 modulated larval locomotion and behavioural anxiety at different ages and adult cortisol levels, but mecp2 null-mutation did not alter adult locomotion and socialization, and developmental sociability and PTZ-induced hyperlocomotion in zebrafish. Given the variability reported in patients and in rodent Mecp2 knockout models, studies using zebrafish can explore vital elements of MECP2's role across development and improve our understanding of neural mechanisms underlying neurodevelopmental disorders.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"38"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression.","authors":"Fengying Zhang, Zhiyi Liu, Yingbin Wang, Lin Zuo, Sicong Xu, Yin Liu, Hao Liang, Yixue Xue","doi":"10.1186/s12868-025-00956-6","DOIUrl":"10.1186/s12868-025-00956-6","url":null,"abstract":"<p><strong>Objective: </strong>Shikonin, an active compound from the rhizome of Lithospermum erythrorhizon, exerts anti-tumor effects in various cancers, including glioblastoma multiforme (GBM). This study explored the mechanism of Shikonin for inhibiting the migration and invasion of GBM cells, providing a rationale for developing novel glioma therapies.</p><p><strong>Methods: </strong>The effects of Shikonin on GBM cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were detected by CCK-8, scratch wound-healing, Transwell, and Western blot assays. The effect of Shikonin on miR-361-5p expression in GBM cells was examined by RT-qPCR and the effect of miR-361-5p inhibitor transfection on proliferation, migration, invasion, and EMT in Shikonin-treated GBM cells was examined. Shikonin's target genes were identified and validated using dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay, focusing on its induction of miR-361-5p expression. The downstream target genes of miR-361-5p were also identified and validated under Shikonin action. A GBM cell nude mouse xenograft tumor was established to confirm the regulatory role of Shikonin.</p><p><strong>Results: </strong>Shikonin inhibited cell proliferation, migration, invasion, and EMT and upregulated miR-361-5p expression in GBM cells. Shikonin upregulated the glioma-associated protein p53, which promoted miR-361-5p transcription. miR-361-5p inhibited ZEB1 expression. Therefore, Shikonin inhibited GBM cell proliferation, migration, invasion, and EMT via p53/ miR-361-5p/ ZEB1 axis in vitro and in vivo.</p><p><strong>Conclusion: </strong>Shikonin suppresses glioma cell proliferation, migration, invasion, and EMT by inhibiting ZEB1 expression through the p53/miR-361-5p axis.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"37"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}