Brain Research Bulletin最新文献

{"title":"Post-traumatic stress disorder-induced behavioral modulation by the medial septum-medial habenula neural pathway","authors":"Yu-Jie Wu ,&nbsp;Ke-Xing Ren ,&nbsp;Kun-Yi Cai ,&nbsp;Chao Zheng ,&nbsp;Ai-Ping Xu ,&nbsp;Hao Luo ,&nbsp;Meng-Ya Wang ,&nbsp;Huan-Huan Zhang","doi":"10.1016/j.brainresbull.2024.111185","DOIUrl":"10.1016/j.brainresbull.2024.111185","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is characterized by anxiety, excessive fear, distress, and weakness as symptoms of a psychiatric disorder. However, the mechanism associated with its symptoms such as anxiety-like behaviors is not well understood. It is aimed to investigate the underlying mechanisms of the medial septum (MS)–medial habenula (MHb) neural circuit modulating the anxiety-like behaviors of PTSD mice through <em>in vivo</em> fiber photometry recording, optogenetics, behavioral testing by open-field and elevated plus maze, fluorescent gold retrograde tracer technology, and viral tracer technology. In the mouse PTSD model induced by compound stress consisting of single-prolonged stress combined with electrical foot shock, the average peak value of the Ca^2 + signals in both the MHb and MS glutamatergic neurons significantly increased. The anterograde and retrograde tracer markers were used to indicate the possible connection between MS and MHb via glutamatergic neural pathway. After the optogenetic manipulation of the MS–MHb pathway in mice with PTSD, if the MS–MHb glutamatergic pathway was inhibited, anxiety was relieved based on changes in the various indices of behavioral experiments in mice with PTSD. Moreover, the heart rate of mice decreased. In conclusion, both glutamatergic neurons located in MS and MHb can be engaged in the development of PTSD anxiety-like behavior, and the MS–MHb can be related to the regulation of PTSD anxiety-like behavior and cardiac function through the glutamatergic neural pathway.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111185"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bindarit attenuates neuroinflammation after subarachnoid hemorrhage by regulating the CCL2/CCR2/NF-κB pathway","authors":"Yanting Yao ,&nbsp;Qiaowei Wu ,&nbsp;Kaikun Yuan ,&nbsp;Pei Wu ,&nbsp;Chao Xu ,&nbsp;Zhiyong Ji ,&nbsp;Weishi Xu ,&nbsp;Hongli Yu ,&nbsp;Anyu Xu ,&nbsp;Yanchen Liu ,&nbsp;Huaizhang Shi","doi":"10.1016/j.brainresbull.2024.111183","DOIUrl":"10.1016/j.brainresbull.2024.111183","url":null,"abstract":"<div><h3>Background and purpose</h3><div>The poor prognosis of subarachnoid hemorrhage (SAH) is closely linked to neuroinflammation and neuronal apoptosis. The CCL2/CCR2 signaling axis, a cytoplasmic pathway responsible for recruiting immune cells, plays a significant role in regulating neuroinflammation in neurological diseases. Bindarit, an inhibitor of chemokine CC motif ligand 2(CCL2), has been shown to demonstrate neuroprotective effects in various central nervous system diseases. This study aimed to investigate the anti-inflammatory effects of Bindarit after SAH.</div></div><div><h3>Methods</h3><div>Pre-processed RNA-seq transcriptome datasets GSE79416 from the Gene Expression Omnibus (GEO) database were analyzed to identify genes differentially expressed between mice with SAH and control mice using bioinformatics methods. Bindarit, a CCL2 inhibitor, was administered intraperitoneally one hour after SAH. Recombinant CCL2 protein was administered via the lateral ventricle one hour before SAH induction. HT22 cells were cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH.</div></div><div><h3>Results</h3><div>Analysis of GSE79416 datasets revealed upregulation of CCL2 expression, identifying it as a hub gene in SAH. Following SAH, CCL2 expression increased in rat brain tissue, reaching the highest level 24 h after SAH. Bindarit improved the short-term and long-term neurological deficits after SAH and also exhibited the anti-inflammatory effects following SAH. Conversely, administration of recombinant CCL2 protein attenuated the protective effects of Bindarit. In vitro, Bindarit significantly reduced neuronal inflammation.</div></div><div><h3>Conclusion</h3><div>Endogenous CCL2 expression was upregulated in the rat SAH model. Bindarit improved neurological functions and reduced neuroinflammation by regulating the CCL2/CCR2/NF-κB pathway in early brain injury after SAH.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111183"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring and validating key genetic biomarkers for diagnosis of Parkinson's disease","authors":"Wen-bin Teng ,&nbsp;Hao-wei Deng ,&nbsp;Bing-hua Lv ,&nbsp;Shao-dan Zhou ,&nbsp;Bin-ru Li ,&nbsp;Rui-ting Hu","doi":"10.1016/j.brainresbull.2024.111165","DOIUrl":"10.1016/j.brainresbull.2024.111165","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is a neurological condition characterized by complex genetic basic, and the reliable diagnosis of PD remained limited.</div></div><div><h3>Objective</h3><div>To identify genes crucial to PD and assess their potential as diagnostic markers.</div></div><div><h3>Methods</h3><div>Differentially expressed genes (DEGs) were screened from the PD tissue dataset and blood dataset. Two machine learning methods were used to identify key PD-related genes. The genes were validated in an independent dataset. Further validation using 120 peripheral blood mononuclear cells (PBMCs) from PD patients. The clinical significance and the diagnostic value of the genes was determined. The function of genes was analyzed and verified by cells experiments.</div></div><div><h3>Results</h3><div>Thirteen common upregulated genes were identified between PD tissue dataset and blood dataset. Two machine learning methods identify three key PD-related genes (GPX2, CR1, ZNF556). An independent dataset and PBMCs samples results showed increased expression in PD patients. Clinical analysis showed that GPX2 and CR1 expression correlated with early-stage PD. The validated dataset of blood samples revealed each three gene showed moderate diagnostic potential for PD, with combined analysis outperforming individual gene analysis (AUC:0.701). The PBMCs samples showed similar diagnostic value of each gene, and the combination of the three genes presented better diagnostic value (AUC:0.801). Functional studies highlighted the involvement of these genes in key pathways in PD pathology. The results of SH-SY5Y cells showed that these three genes increased from PD cell model.</div></div><div><h3>Conclusions</h3><div>GPX2, CR1, ZNF556 were critical to the development of PD and might serve as diagnostic markers for PD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111165"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSATB2 modulates fear extinction memory via Robo3-driven synaptic plasticity","authors":"Ziyue Xu ,&nbsp;Jichun Shi ,&nbsp;Runming Liu ,&nbsp;Zhehao Li ,&nbsp;Shuangxiang Xu ,&nbsp;Hao Gong ,&nbsp;Mingyue Fu ,&nbsp;Hongyu Xu ,&nbsp;Shuangqi Yu ,&nbsp;Junhui Liu ,&nbsp;Huiqing Wu ,&nbsp;Xiang Li ,&nbsp;Sha Liu ,&nbsp;Wei Wei","doi":"10.1016/j.brainresbull.2024.111167","DOIUrl":"10.1016/j.brainresbull.2024.111167","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) are novel class of stable regulatory RNAs abundantly expressed in the brain. However, their role in fear extinction (EXT) memory remains largely unexplored. To investigate the mechanisms of Circular Special AT-rich Sequence Binding Protein 2 (circSatb2) in EXT memory, we constructed a lentivirus overexpressing circSatb2 and injected it into the infralimbic prefrontal cortex (ILPFC) of the mouse brain. Following extinction training and subsequent testing, we observed an essential role of circSatb2 in this dynamic process. RNA sequencing (RNA-seq) and bioinformatics analyses revealed that circSatb2 enhances the transcription of Roundabout Guidance Receptor 3 (Robo3), a key gene implicated in axon guidance and synaptic plasticity, which was validated by RT-qPCR. Neuronal morphology was assessed using confocal microscopy to determine changes in dendritic spine density. Our results demonstrated that circSatb2 significantly enhances Robo3 transcription, leading to increased dendritic spine formation and improved synaptic plasticity. In conclusion, circSatb2 promotes the formation of EXT memory by upregulating Robo3 transcription and enhancing synaptic plasticity. These findings position circSatb2 as a potential therapeutic target for disorders associated with memory impairment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111167"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forsythoside B ameliorates neuroinflammation via inhibiting NLRP3 inflammasome of glial cells in experimental autoimmune encephalomyelitis mice","authors":"Yue Wang ,&nbsp;Yongmin Chen ,&nbsp;Jing Lu ,&nbsp;Qinqin Xiao ,&nbsp;Ge Li ,&nbsp;Rong Wang ,&nbsp;Rong Chen ,&nbsp;Da-Qi Zhang","doi":"10.1016/j.brainresbull.2024.111182","DOIUrl":"10.1016/j.brainresbull.2024.111182","url":null,"abstract":"<div><div>Neuroinflammation mediated by glial cells plays a crucial role in demyelination in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Forsythoside B (FTS·B), a natural phenylethanoid glycoside isolated from the dried fruits and leaves of Forsythia suspensa (Thunb.) Vahl, has been found to have antioxidant, anti-apoptotic, and anti-inflammatory properties. However, there is currently no report or research on the effectiveness of FTS·B treatment for EAE. The aim of this study was to investigate the neuroprotective properties of (FTS·B) on EAE and reveal its potential mechanisms. Myelin oligodendrocyte glycoprotein-induced EAE mice were randomly categorized into the control, EAE model, and FTS·B treatment groups. Behavioral testing, pathology, immunohistochemistry, immunofluorescence staining, and western blot analysis of spinal cord tissue were used to determine the effects and mechanisms of FTS·B on EAE in mice. We found that FTS·B treatment could significantly alleviate and reduce the clinical symptoms and morbidity of EAE, respectively. In addition, FTS·B administration reduced inflammatory response and demyelination by inhibiting glial cell activation in the spinal cord of EAE mice. Further experiments confirmed that FTS·B inhibited the formation of NLRP3 inflammasome in microglia and astrocytes, thereby suppressing neuroinflammation and GSDMD-mediated pyroptosis. Altogether, these results suggest that FTS·B treatment attenuates central neuroinflammation and pyroptosis by inhibiting NLRP3 inflammasome of glial cells in EAE mice.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111182"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single high-frequency repetitive transcranial magnetic stimulation and intermittent theta pulse stimulation promote working memory behavior in participants: An event-related potential study","authors":"Longting Hu ,&nbsp;Jinyan He ,&nbsp;Menglin Han ,&nbsp;Zhiqiang Wang ,&nbsp;Yulan Gao ,&nbsp;Boyu Zhang ,&nbsp;Shuyan Zhou ,&nbsp;Kangling Wang ,&nbsp;Shuning Li ,&nbsp;Xuan Wu","doi":"10.1016/j.brainresbull.2024.111147","DOIUrl":"10.1016/j.brainresbull.2024.111147","url":null,"abstract":"<div><h3>Objective</h3><div>Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) has an improving effect in cognitive function, but it is still not clear in what specific cognitive domains. We here combined a single session of TMS (HF-rTMS/iTBS) with electroencephalography (EEG) to clarify the effects of magnetic stimulation techniques on executive function, working memory, and visuospatial attention in healthy participants, and to investigate the underlying neurophysiological mechanisms.</div></div><div><h3>Methods</h3><div>Fifty-one healthy participants were randomly assigned to three stimulation groups (HF-rTMS, iTBS, and sham groups). Classical psychological paradigms (task-switching, 2-back with visual Oddball) and event-related potentials (ERPs) were performed to compare the behavioral indices of each paradigm before and after the two stimulations, as well as the changes in the ERP components.</div></div><div><h3>Results</h3><div>Analysis of behavioral indicators showed that reaction times in the 2-back paradigm were faster after HF-rTMS and iTBS than after sham stimulation. However, no statistically significant differences were observed in the behavioral changes in the task-switching and visual Oddball paradigms. ERP analysis showed that N2 amplitude in the frontal and central regions of the participants increased during the 2-back paradigm following HF-rTMS and iTBS; however, no statistically significant differences were observed between the ERP components of the task-switching and visual Oddball paradigms.</div></div><div><h3>Conclusion</h3><div>Single sessions of HF-rTMS and iTBS on the L-DLPFC specifically enhanced working memory performance, with no significant effects on executive function and visuospatial attention. Both true stimulations elicited more negative N2 in the frontal and central channels during the 2-back paradigm, suggesting increased recruitment of cognitive resources from these brain areas. Although iTBS and HF-rTMS improved working memory behavior, iTBS’s shorter stimulation time suggests it may have greater potential for clinical applications in terms of time-benefit costs.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111147"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis","authors":"Jinyun Ma,&nbsp;Xiaojun Liu,&nbsp;Yan Zhao,&nbsp;Qijin Lu,&nbsp;Guiqing Ding,&nbsp;Yuanhua Wang,&nbsp;Xiaodong Cheng","doi":"10.1016/j.brainresbull.2024.111171","DOIUrl":"10.1016/j.brainresbull.2024.111171","url":null,"abstract":"<div><div>The Th17/Treg imbalance is an important cause of immune cell infiltration into the central nervous system (CNS) in multiple sclerosis (MS). The gut microbiota affects the Th17/Treg balance in the gut and in distal areas, such as the CNS, which further contributes to the onset and progression of MS. Our previous studies have shown that <em>Astragalus polysaccharide</em> (APS) has a role in alleviating the clinical symptoms and demyelination of experimental autoimmune encephalomyelitis (EAE) mice, a classic MS model. However, the mechanism of action is not fully understood. In this study, we found that APS suppressed inflammation and regulated the Th17/Treg balance in the CNS and peripheral blood of EAE mice. It was further shown that APS inhibited gut inflammation and reduced Th17 function. The experiment with an antibiotic cocktail interfering with the gut microbiota proved that APS alleviated EAE by regulating the gut microbiota. Through 16S rRNA sequencing, we showed that APS regulated gut microbiota diversity and composition in EAE mice. Then, we found that APS regulated metabolite composition in feces and plasma, thus altering gut and blood metabolic functions. Metabolites related to this pathway, including sphingosine 1 phosphate (S1P), prostaglandin E2 (PGE2), ADP, and ATP, were downregulated by APS. The levels of bile acid metabolites such as taurochenodeoxycholate-7-sulfate and N-palmitoyl aspartic acid were upregulated by APS. In summary, our study demonstrated that APS exerts a suppressive effect on EAE by regulating gut microbiota composition, affecting metabolite composition, and improving the Th17/Treg balance in the peripheral blood and CNS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111171"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of H3K27 acetylation in oxygen-glucose deprivation-induced spinal cord injury and potential for neuroprotective therapies","authors":"Jing Wang ,&nbsp;Zheng Guan ,&nbsp;Weina Li ,&nbsp;Yu Gong ,&nbsp;Heying Wang ,&nbsp;Ting Zhou ,&nbsp;Jingjie Liu","doi":"10.1016/j.brainresbull.2024.111152","DOIUrl":"10.1016/j.brainresbull.2024.111152","url":null,"abstract":"<div><h3>Objective</h3><div>Spinal cord injury (SCI) is a debilitating condition that often results in paralysis and lifelong medical challenges. Research has shown that epigenetic modifications, particularly histone acetylation, play a role in neuroprotection following hypoxic-ischemic events in SCI. The objective of this study was to explore the effects of histone H3K27 acetylation, along with its underlying mechanisms, on the tolerance to hypoxia and ischemia in SCI.</div></div><div><h3>Methods</h3><div>This study employed an organotypic spinal cord slice culture model subjected to oxygen-glucose deprivation (OGD). We assessed cell apoptosis and changes in cellular type patterns under these conditions. Following hypoxia and ischemia, we analyzed the expression and distribution of H3K27ac across various nerve cell types. To identify key downstream genes, we integrated ChIP-seq and RNA-seq analyses, investigating molecular mechanisms driving the response to OGD in this model.</div></div><div><h3>Results</h3><div>OGD stimulation increased cell apoptosis and induced time-dependent changes in the expression patterns of neurons, astrocytes, microglia, and oligodendrocytes in organotypic spinal cord slices, accompanied by a significant reduction in H3K27ac levels. Integrated ChIP-seq and RNA-seq analyses revealed that H3K27ac downregulation under hypoxic and ischemic conditions contributes to spinal cord damage by promoting neuroinflammation and disrupting gene regulation. Furthermore, we identified key downstream targets, including <em>Apoc1</em>, <em>Spp1</em>, <em>Aff1</em>, <em>Brd4</em>, <em>KCNN3</em>, and <em>Rgma</em>, which may represent promising therapeutic targets for SCI.</div></div><div><h3>Conclusion</h3><div>Our data underscore the pivotal role of H3K27ac in the organotypic spinal cord slice culture model following OGD exposure, offering promising avenues for neuroprotective therapies via epigenetic-immune regulation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111152"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural changes in early-stage Parkinson’s disease with resting tremor at node, edge and network level","authors":"Yuke Zhong,&nbsp;Ying Liu,&nbsp;Huahua Su,&nbsp;Hang Liu,&nbsp;Guohui Liu,&nbsp;Zhihui Liu,&nbsp;Jiahao Wei,&nbsp;Junyi Wang,&nbsp;Yuchen She,&nbsp;Changhong Tan,&nbsp;Lijuan Mo,&nbsp;Lin Han,&nbsp;Fen Deng,&nbsp;Xi Liu,&nbsp;Lifen Chen","doi":"10.1016/j.brainresbull.2024.111169","DOIUrl":"10.1016/j.brainresbull.2024.111169","url":null,"abstract":"<div><h3>Background</h3><div>Resting tremor in Parkinson’s disease (PD) is associated with the activity in the basal ganglia and cerebello-thalamo-cortical circuits/network. However, most insights stem from functional MRI research, and structural studies, which can provide basis for and constrain functional activity, remains limited.</div></div><div><h3>Methods</h3><div>We investigated the structural change in PD patients with resting tremor (PD-W<em>R</em>) from a network perspective. 42 early-stage PD-W<em>R</em>, 27 PD patients without resting tremor (PD-NR), and 56 healthy controls (HC) were included.</div></div><div><h3>Results</h3><div>PD-W<em>R</em> showed lower cortical thickness in several motor-related lobules. Compared to HC, significant atrophy was found in right lobule VIIA (t = -3.076, p = 0.016, Cohen's d = 0.627), left lobule VI (t = -3.323, p = 0.007, Cohen's d = 0.678), and right lobule VI (t = -3.052, p = 0.017, Cohen's d = 0.623) in PD-W<em>R</em>. Compared to PD-NR, left lobule V also had a significant reduction (t = -2.958, p = 0.023, d = −0.657). PD-W<em>R</em> had higher fractional anisotropy in cerebello-cortical connection compared to HC (t = 3.209, p = 0.009, d = 0.926), with reduced radial (t = -2.561, p = 0.046, d = 0.739) and mean (t = 2.614, p = 0.046, d = 0.871) diffusivity compared to PD-NR. At the network level, better hierarchy (rho = 0.598, p = 0.004), small-worldness (rho = 0.621, p = 0.003), and increased nodal involvement of the thalamus (rho = 0.718, p = 0.031) and motor cortex (rho = 0.660, p = 0.055) were positively correlated with tremor amplitude.</div></div><div><h3>Conclusion</h3><div>Our study supports the alternation of the cerebello-thalamo-cortical circuit in PD-W<em>R</em>. However, further research with other forms of PD, a wide range of disease stage and larger sample size is needed.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111169"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture inhibits neuronal pyroptosis in ischemic brain injury through modulating SIRT5-mediated NEK7 succinylation","authors":"Lili Ma ,&nbsp;Meiling Zhang ,&nbsp;Ting Chen ,&nbsp;Limin Wang ,&nbsp;Qilong Deng","doi":"10.1016/j.brainresbull.2024.111173","DOIUrl":"10.1016/j.brainresbull.2024.111173","url":null,"abstract":"<div><div>Ischemic stroke is a leading cause of global death. The treatment of this disease can inevitably result in reperfusion, thereby triggering cerebral ischemia-reperfusion injury (IRI) and neuronal pyroptosis. Electroacupuncture derived from traditional acupuncture has been proven to have favorable effects on ameliorating brain IRI and pyroptosis. Hence, the goal of the current research was to elucidate the mechanism governing electroacupuncture in cerebral IRI. We employed middle cerebral artery occlusion (MCAO) model to induce brain IRI. Our results revealed that electroacupuncture attenuated IRI in MCAO mice by minishing brain damage and hindering neuronal pyroptosis. Strikingly, it was discovered that electroacupuncture provoked the decrease of succinylation level and enhanced expression of SIRT5. Then, we demonstrated that knockdown of SIRT5 reversed the role of electroacupuncture in cerebral infarct injury and pyroptosis. In terms of mechanism, SIRT5 impeded the succinylation modification of NEK7 at K81 site to downregulate its expression level. Eventually, overexpression of NEK7 abrogated the impacts of electroacupuncture on MCAO mice. In conclusion, electroacupuncture restrained neuronal pyroptosis after cerebral ischemia via desuccinylating NEK7 in a SIRT5-dependent way.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"220 ","pages":"Article 111173"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}