Brain Research Bulletin最新文献

{"title":"An experimental study on the optimal timing of modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats","authors":"Qianqian Wang ,&nbsp;Jiahui Hu ,&nbsp;Yueqin Tian ,&nbsp;Chao Li ,&nbsp;Nenggui Xu ,&nbsp;Hongmei Wen ,&nbsp;Zulin Dou ,&nbsp;Qiuping Ye","doi":"10.1016/j.brainresbull.2025.111390","DOIUrl":"10.1016/j.brainresbull.2025.111390","url":null,"abstract":"<div><div>As a novel neuroregulatory technique, modified pharyngeal electrical stimulation (mPES) has demonstrated clinical potential in improving swallowing function. However, there is a notable lack of animal studies exploring this approach. While our previous research validated the optimal parameters for post-stroke dysphagia (PSD) in rats, it did not establish the ideal timing for initiating treatment. This study aimed to identify the optimal time for mPES treatment in the rehabilitation of PSD. Seventy-four Sprague-Dawley (SD) rats were randomly assigned to six groups: a model group, a sham group, and four mPES groups (with treatment initiated at 24 h, 72 h, 5 days, and 7 days post-modeling). All treatment groups received mPES therapy for three consecutive days. Following the intervention, swallowing function was re-evaluated using videofluoroscopic swallowing studies (VFSS), and western blotting analysis was conducted to assess the excitability of sensorimotor cortex. Compared to the model group, all mPES groups exhibited improvements in swallowing function. Among them, the group receiving treatment 72 h post-modeling demonstrated the most significant enhancements (<em>P &lt; 0.05</em>). In addition, The expressions of N-methyl-D-aspartic acid receptor (NMDAR1) and Vesicular glutamate transporter 2 (Vglut2) were higher in the 72-hour group compared to the 7 day group (<em>P &lt; 0.05</em>). This study concluded that mPES treatment was effective when initiated at any of the tested time points-24 h, 72 h, 5 days, or 7 days post-modeling. However, initiating treatment 72-hour post-modeling yielded the greatest improvement in swallowing function in PSD rats.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111390"},"PeriodicalIF":3.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential risk factors of susceptibility to recurrent depression","authors":"Shuzhuo Wang ,&nbsp;Lei Guo ,&nbsp;Chuang Wang","doi":"10.1016/j.brainresbull.2025.111374","DOIUrl":"10.1016/j.brainresbull.2025.111374","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in the BicC family RNA binding protein 1 (BICC1). However, the potential risk factors that regulate BICC1 and affect susceptibility to recurrent depression remain unclear.</div></div><div><h3>Methods</h3><div>Herein, we firstly tested the heat shock protein 90 (HSP90), hypoxia-inducible factor 1-alpha (HIF1α), and BICC1 in the serum of the patients that were in first-episode or recurrent depression, as well as their controls. Then, through re-exposure to chronic unpredictable mild stress (CUMS) in mice, an animal model of recurrent depression was assessed. And the expression of HSP90, HIF1α, and BICC1 in the prefrontal cortex (PFC) were analyzed.</div></div><div><h3>Results</h3><div>We found that HSP90, HIF1α, and BICC1 were significantly increased in the serum of depressed patients, especially in those with recurrent depression, indicating that these molecules may serve as specific pathogenetic risk factors for depression, especially depression recurrence. In addition, the recurrent depression mice model was found to be accompanied by a significant increase in expression of HSP90, HIF1α and BICC1 in the PFC.</div></div><div><h3>Conclusions</h3><div>The current study identified HSP90, HIF1α, and BICC1 as novel potential risk factors that affect susceptibility to recurrent depression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111374"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myricetin alleviates learning and memory deficits in trimethyltin Alzheimer’s phenotype via attenuating hippocampal endoplasmic reticulum stress and regulating inflammation and oxidative stress","authors":"Zahra Asgari ,&nbsp;Saeid Iranzadeh ,&nbsp;Mehrdad Roghani","doi":"10.1016/j.brainresbull.2025.111382","DOIUrl":"10.1016/j.brainresbull.2025.111382","url":null,"abstract":"<div><div>Trimethyltin hydrochloride (TMT) induces hippocampal neurodegeneration and learning and memory impairments, providing a useful experimental model for Alzheimer's disease (AD) research. This study aimed to explore the neuroprotective effects of myricetin, a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, against TMT-induced hippocampal damage and elucidate some of its underlying molecular mechanisms. Male NMRI mice (n = 32) were divided into four experimental groups: control, control + myricetin, TMT, and TMT + myricetin. Neurodegeneration was induced by intraperitoneal TMT injection (2.8 mg/kg), followed by daily oral administration of myricetin (25 mg/kg) for 21 days. Learning and memory-related function was assessed using passive avoidance, novel object recognition, and Y-maze tests. After behavioral tasks, hippocampal levels of oxidative stress parameters (glutathione (GSH), superoxide dismutase (SOD), catalase, malondialdehyde (MDA)), inflammatory markers (tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10)), and endoplasmic reticulum stress pathway proteins (GRP78, PERK, IRE1α, and CHOP) were evaluated. Histological examinations included Nissl staining to quantify neuronal degeneration in CA1 and dentate gyrus regions, as well as glial fibrillary acidic protein (GFAP) immunohistochemistry. Myricetin treatment attenuated TMT-induced learning and memory impairments and neuronal loss in the CA1 and dentate gyrus subfields. It significantly enhanced hippocampal levels of GSH, SOD and catalase activities, and IL-10 while reducing levels of MDA, TNF-α, and GFAP immunoreactivity. Moreover, myricetin alleviated the TMT-induced elevation of GRP78, PERK, IRE1α, and CHOP. These findings suggest that myricetin holds promise as a therapeutic candidate for AD and other neurodegenerative disorders by counteracting oxidative stress, suppressing neuroinflammation, and modulating endoplasmic reticulum stress pathways.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111382"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporation of graphene oxide into collagenous biomaterials attenuates scar-forming phenotype transition of reactive astrocytes in vitro","authors":"Kest Verstappen ,&nbsp;Alexey Klymov ,&nbsp;Paula A.A.P. Marques ,&nbsp;Sander C.G. Leeuwenburgh ,&nbsp;X. Frank Walboomers","doi":"10.1016/j.brainresbull.2025.111380","DOIUrl":"10.1016/j.brainresbull.2025.111380","url":null,"abstract":"<div><div>The integrin-mediated interaction between collagen type I and reactive astrocytes was recently shown to induce a detrimental, scar-forming phenotype transformation following spinal cord injury (SCI), which severely limits the therapeutic potential of commonly used collagen-based biomaterials. Graphene oxide (GO) is a promising candidate to disrupt the collagen-integrin interaction, since it is capable of altering the surface topography of biomaterials applied as SCI treatment. Moreover, free GO contributes towards potassium and glutamate transport, which is often implicated following SCI. However, it remains unclear whether both the integrin-mediated binding and astrocytic transport of potassium and glutamate are affected by GO, when inserted into collagenous biomaterials. Therefore, in the current study GO was incorporated into collagen-based hydrogels in an attempt to prevent the scar-forming phenotype transition and promote the expression of astrocytic potassium channels and glutamate transporters. Primary astrocytes were cultured either on top of or embedded within GO-enriched collagen type I or adipose tissue-derived extracellular matrix (ECM) gels. The impact of GO incorporation on integrin β1-mediated binding, astrocyte phenotype and potassium and glutamate transport was assessed by gene expression analysis and immunofluorescence studies. Upon GO incorporation into ECM gels, expression of integrin β1 and N-cadherin was significantly decreased. Moreover, GO decreased proteoglycan-associated gene expression by four-fold. Finally, GO incorporation led to a decrease in expression of both potassium channels and glutamate transporters. In conclusion, the incorporation of GO into collagen-based materials attenuated the transition of reactive astrocytes into a scar-forming phenotype.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111380"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Brain endothelial CD200 signaling protects brain against ischemic damage” [Brain Res. Bull. 207 (2024) 110864]","authors":"Afzal Misrani,&nbsp;Conelius Ngwa,&nbsp;Abdullah Al Mamun,&nbsp;Romana Sharmeen,&nbsp;Kanaka Valli Manyam,&nbsp;Rodney M. Ritzel,&nbsp;Louise McCullough,&nbsp;Fudong Liu","doi":"10.1016/j.brainresbull.2025.111384","DOIUrl":"10.1016/j.brainresbull.2025.111384","url":null,"abstract":"","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111384"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting the rich dialogue between astrocytes and neurons: An overview in Rett syndrome","authors":"Francesca M. Postogna,&nbsp;Ottavia M. Roggero,&nbsp;Fabio Biella,&nbsp;Angelisa Frasca","doi":"10.1016/j.brainresbull.2025.111386","DOIUrl":"10.1016/j.brainresbull.2025.111386","url":null,"abstract":"<div><div>Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily affecting females, with an incidence of 1 in 10,000 live births. It is caused mainly by <em>de novo</em> mutations in the X-linked <em>MECP2</em> gene, which encodes methyl-CpG binding protein 2 (<em>Mecp2</em>), a key epigenetic regulator. <em>MECP2</em> mutations have profound impacts on neurons, which exhibit morphological, synaptic and functional impairments. However, more recent evidence highlights a crucial role of astrocytes in RTT pathogenesis. Indeed, RTT astrocytes exhibit structural and functional impairments, failing to support neuronal growth and function through non-cell autonomous mechanisms. Studies reveal that <em>MECP2</em> deficient astrocytes secrete abnormal factors that impair neuronal growth and synaptic function. Furthermore, they show dysregulated calcium signalling, disrupted glutamate and potassium homeostasis, and increased inflammatory responses, all of which contribute to neuronal dysfunction. Understanding these neuron-astrocyte interactions may offer novel therapeutic targets for RTT. In the review we aim at presenting the current knowledge of astrocyte-neuron crosstalk in RTT, describing the different mechanisms highlighted so far through which <em>MECP2</em> mutant astrocytes impair neurons. Finally, we discuss existing and prospective methodological approaches for investigating cell-to-cell communication in RTT.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111386"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-669f-5p targeting deoxycytidinephosphate deaminase contributes to sevoflurane-induced cognitive impairments in aged mice via the TLR2/4–MyD88–NF-κB pathway","authors":"Yuanping Zhong ,&nbsp;Chao Zhang ,&nbsp;Yuan Li ,&nbsp;Dongqin Chen ,&nbsp;Chunchun Tang ,&nbsp;Xue Zheng ,&nbsp;Zhaoqiong Zhu","doi":"10.1016/j.brainresbull.2025.111381","DOIUrl":"10.1016/j.brainresbull.2025.111381","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) is a common complication associated with sevoflurane anaesthesia in the aged population. MicroRNAs have been implicated in sevoflurane-induced cognitive deficits; however, the role and underlying mechanism of microRNA (miR)-669f-5p remain unclear.</div></div><div><h3>Methods</h3><div>Eighteen-month-old mice and mouse hippocampal neurons (HT22) were exposed to sevoflurane. Cognitive function was assessed using the Morris water maze test. Neuroapoptosis and cellular proliferation were evaluated by terminal-deoxynucleotidyl transferase-mediated nick end-labelling staining and Cell Counting Kit-8 assays, respectively. The downstream molecular mechanisms of miR-669f-5p were investigated using bioinformatics analysis, western blotting, quantitative real-time polymerase chain reaction, immunofluorescence and dual-luciferase reporter assays.</div></div><div><h3>Results</h3><div>Bioinformatics analysis of the Gene Expression Omnibus database revealed upregulation of miR-669f-5p in hippocampal tissue from mice with POCD. Inhibition of miR-669f-5p substantially improved sevoflurane-induced cognitive impairment in aged mice. Deoxycytidinephosphate deaminase (Dctd) was identified as a direct target of miR-669f-5p. Overexpression of Dctd reversed the effects of miR-669f-5p mimics on apoptosis and proliferation in HT22 cells and suppressed activation of the TLR2/4–MyD88–NF-κB signalling pathway. Moreover, Dctd overexpression ameliorated sevoflurane-induced cognitive impairment in aged mice.</div></div><div><h3>Conclusion</h3><div>MicroRNA-669f-5p contributes to sevoflurane-induced cognitive impairment in aged mice by targeting Dctd and activating the TLR2/4–MyD88–NF-κB pathway. These findings provide new insights into potential therapeutic strategies for anaesthesia-related POCD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111381"},"PeriodicalIF":3.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury","authors":"Qingqin Xu ,&nbsp;Zhongfu Zhang ,&nbsp;Yuqing Zhai ,&nbsp;Ji Chen ,&nbsp;Jianhua Xu ,&nbsp;Hemu Chen ,&nbsp;Jianwei Lu","doi":"10.1016/j.brainresbull.2025.111385","DOIUrl":"10.1016/j.brainresbull.2025.111385","url":null,"abstract":"<div><h3>Background</h3><div>Previous therapies for spinal cord injury (SCI) typically focus on the lesion site, neglecting the interconnected brain areas. Transcranial magnetic stimulation (TMS) is an emerging non-invasive neuromodulation technique, demonstrating potential in modulating the primary motor cortex to enhance SCI recovery.</div></div><div><h3>Methods</h3><div>The modified Allen's method was used to establish an SCI rat model. High-frequency repetitive TMS (HF-rTMS) intervention was initiated on the second day after modeling and continued for 56 days. Bioinformatics analysis identified key genes involved in the SCI pathological process, including MMP9, IL-1β, and IL-18. This study explored the functions and mechanisms of these genes in HF-rTMS-mediated motor recovery in SCI rats.</div></div><div><h3>Results</h3><div>Western blotting reveals that HF-rTMS decreases active-MMP9/pro-MMP9, TNF-α, IL-1β, and IL-18 proteins' expression, while increases β-DG, Occludin, Claudin-5, and ZO-1 proteins' expression in injured spinal cord (<em>P</em> &lt; 0.001). Immunofluorescence staining further shows that HF-rTMS reduces MMP9 positive cells, while enhances Occludin, Claudin-5, and ZO-1 positive cells (<em>P</em> &lt; 0.001). Evans Blue staining indicates that HF-rTMS reduces blood-spinal cord barrier (BSCB) permeability following injury, while ELISA results demonstrate that HF-rTMS attenuates serum levels of pro-inflammatory cytokines. Motor-evoked potentials (MEP) assessment, HE staining, and BBB score show that HF-rTMS shortens MEP latency, enhances MEP amplitude, reduces spinal cord damage and improves motor function (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>These findings reveal that HF-rTMS may be associated with suppressing MMP9 activation, protecting tight junction proteins, diminishing basement membrane destruction, and maintaining BSCB integrity. Simultaneously, it may alleviate pro-inflammatory cytokine-induced inflammation, thereby reducing spinal cord tissue damage and promoting motor recovery after SCI.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111385"},"PeriodicalIF":3.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury","authors":"Tianying Li ,&nbsp;Guanwen Lin ,&nbsp;Tao Zhang ,&nbsp;Yani Guo ,&nbsp;Yongjin He ,&nbsp;Jing Luan ,&nbsp;Jin Wang ,&nbsp;Dan Lyu ,&nbsp;Yiqi Weng ,&nbsp;Xin Jin","doi":"10.1016/j.brainresbull.2025.111383","DOIUrl":"10.1016/j.brainresbull.2025.111383","url":null,"abstract":"<div><h3>Background and aim</h3><div>Neuropathic pain (NP), caused by nerve injury or dysfunction, poses a significant clinical challenge due to its limited response to conventional pharmacological treatments. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive neuromodulatory approach for NP management. This study aimed to evaluate the therapeutic efficacy of rTMS in alleviating NP induced by chronic constriction injury (CCI) in a mouse model and to investigate the underlying molecular mechanisms through transcriptomic profiling.</div></div><div><h3>Procedures</h3><div>Adult male mice underwent CCI surgery to induce NP and were randomly assigned to receive either rTMS (5 Hz or 10 Hz) or sham stimulation. rTMS was applied once daily for 14 consecutive days, beginning on postoperative day 7. Behavioral assessments—including paw withdrawal latency (PWL) and paw withdrawal threshold (PWT)—were conducted to evaluate thermal hyperalgesia and mechanical allodynia, respectively. Anxiety-like behaviors were assessed using the open field test (OFT) and elevated plus maze (EPM). At the end of the treatment period, brain tissues were harvested for RNA sequencing and differentially expressed genes (DEGs) were identified and analyzed.</div></div><div><h3>Results and conclusion</h3><div>rTMS at both 5 Hz and 10 Hz significantly improved PWL and PWT in CCI mice and reduced anxiety-like behaviors. Transcriptomic analysis revealed that CCI induced dysregulation of 66 genes, while rTMS partially normalized gene expression patterns. Functional enrichment analysis indicated significant involvement of pathways related to inflammatory responses, transporter activity, and ion channel regulation. These findings support the potential of rTMS as a multifaceted, non-invasive therapeutic strategy for neuropathic pain, with molecular mechanisms likely involving modulation of neuroinflammatory and neuroexcitatory pathways.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111383"},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute changes in functional connectivity associated with first osteopathic manual treatment in chronic low back pain spatially overlap with opioid receptor expression","authors":"Federica Tomaiuolo ,&nbsp;Francesco Cerritelli ,&nbsp;Carlo Sestieri ,&nbsp;Jordan Keys ,&nbsp;Teresa Paolucci ,&nbsp;Stefano L. Sensi ,&nbsp;Antonio Ferretti ,&nbsp;Stefano Delli Pizzi","doi":"10.1016/j.brainresbull.2025.111375","DOIUrl":"10.1016/j.brainresbull.2025.111375","url":null,"abstract":"<div><h3>Background</h3><div>Osteopathic Manipulative Treatment (OMT) has emerged as a therapeutic approach for chronic low back pain (cLBP). Previous Magnetic Resonance (MR) studies have demonstrated that four weeks of OMT alter resting-state functional connectivity (rs-FC) in the somatosensory cortex, prefrontal regions, and frontal operculum/insula. However, it remains unclear whether a single session of OMT can immediately affect brain rs-FC.</div></div><div><h3>Methods</h3><div>We combined a data-driven approach with a seed-based connectivity analysis to examine the pattern of whole-brain rs-FC in a cohort of thirty cLBP patients before and after a first acute session of OMT (N = 16) or a sham treatment (N = 14). Correlation analyses were performed to explore the relationship between the resulting rs-FC maps and receptor density/gene expression maps derived from in vivo brain atlases, focusing on the opioid and cannabinoid systems.</div></div><div><h3>Results</h3><div>Data-driven analysis revealed that, compared to the sham group, the OMT increased the intrinsic connectivity of the right dorsolateral prefrontal cortex. Seed-based connectivity analysis showed that this region increased coupling with the right frontal operculum/insula. Notably, no effect of immediate OMT was found in the somatosensory cortex. The topography of these rs-FC changes selectively overlapped with the distribution of mu-opioid receptors.</div></div><div><h3>Conclusions</h3><div>Acute OMT in cLBP patients modulates rs-FC across cortical regions primarily involved in top-down cognitive control of pain, as well as in integrating pain intensity perception and related expectations. Spatial comparisons between rs-FC maps and receptor atlases suggest that these neural changes involve opioid, not cannabinoid, neurotransmission.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111375"},"PeriodicalIF":3.5,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}