Brain Research Bulletin最新文献

{"title":"Structural and functional connectivity coupling as an imaging marker for bone metastasis pain in lung cancer patients","authors":"Jiahui Zheng ,&nbsp;Chengfang Wang ,&nbsp;Xiaoyu Zhou ,&nbsp;Yu Tang ,&nbsp;Lin Tang ,&nbsp;Yong Tan ,&nbsp;Jing Zhang ,&nbsp;Hong Yu ,&nbsp;Jiuquan Zhang ,&nbsp;Daihong Liu","doi":"10.1016/j.brainresbull.2025.111210","DOIUrl":"10.1016/j.brainresbull.2025.111210","url":null,"abstract":"<div><h3>Background</h3><div>Cancer pain is a common symptom in patients with malignant tumors and associated with poor prognosis and a high risk of death. Structural connectivity (SC) and functional connectivity (FC) couplings have not yet been explored in lung cancer patients with bone metastasis pain.</div></div><div><h3>Methods</h3><div>In total, 51 patients with lung cancer without bone metastasis pain (BMP–), 52 patients with lung cancer with bone metastasis pain (BMP+), and 28 healthy controls (HC) were prospectively enrolled in our study. Firstly, SC–FC couplings were measured and analyzed at global, regional, and modular levels. Subsequently, individualized SC-FC coupling networks were constructed based on the Euclidean distance metric. In addition, the convolutional neural network (CNN) model was selected to analyze and classify three groups based on individualized networks.</div></div><div><h3>Results</h3><div>The coupling analysis demonstrated that weaker SC–FC couplings related to lung cancer itself were present at various levels, including global, regional, inter-network, and intra-network couplings. Notably, hyper-couplings related to bone metastasis pain were present in several brain regions, mainly involving the default mode network, frontoparietal network, salience network, and limbic system. Significant positive correlations were observed between regional coupling in the right amygdala and the numeric rating scale scores in BMP+. Moreover, CNN model built on individualized networks exhibited relatively great classification performance.</div></div><div><h3>Conclusion</h3><div>Alterations in SC–FC coupling patterns may play a crucial role in the development and modulation of bone metastasis pain. Understanding these changes could provide valuable insights into the neural mechanisms underlying cancer pain.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111210"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000573","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":"Altered resting-state cerebral blood flow and its relationship with molecular architecture in tremor dominant Parkinson’s disease","authors":"Shangpei Wang ,&nbsp;Yajie Cai ,&nbsp;Yibin Zhao ,&nbsp;Yongqiang Yu ,&nbsp;Xianwen Chen ,&nbsp;Longsheng Wang","doi":"10.1016/j.brainresbull.2025.111237","DOIUrl":"10.1016/j.brainresbull.2025.111237","url":null,"abstract":"<div><h3>Background</h3><div>The resting-state cerebral blood flow (CBF) alterations in Parkinson’s disease (PD) patients and tremor-dominant (TD) subtype have been explored. However, the underlying molecular architecture correlated with the altered CBF remains unknown.</div></div><div><h3>Methods</h3><div>In total, 90 PD patients including 41 TD subtype, and 90 healthy controls (HC) underwent arterial spin labelling magnetic resonance image. The altered CBF were derived by a voxel-wised two sample <em>t</em>-test compare and spatial correlated with serotonin, dopamine, γ-aminobutyric acid, opioid, noradrenaline, N-methyl-D-aspartic acid, acetylcholine and glutamate neurotransmitter density maps.</div></div><div><h3>Results</h3><div>Compared to HC, PD patients exhibited decreased CBF in left caudate/putamen, increased CBF in bilateral supplementary motor area (SMA). Moreover, the CBF of SMA showed a positive correlation with disease severity. The altered CBF in PD patients were significantly associated with spatial distribution of serotonin 5-hydroxytryptamine receptor, dopamine receptor, and noradrenaline transporter. Compared to non-tremor-dominant subtype, the TD subtype exhibited decreased CBF in left calcarine/cuneus, increased CBF in left middle frontal gyrus and bilateral superior frontal gyrus. The altered CBF in the TD subtype were significantly associated with spatial distribution of serotonin 5-hydroxytryptamine, dopamine, glutamate, and opioid receptors.</div></div><div><h3>Conclusions</h3><div>Besides dopamine, perfusion alterations in SMA of PD patients were more probably correlated with serotonin and noradrenaline. Perfusion alterations of the TD subtype were related to dopamine, serotonin, other excitatory neurotransmitters such as glutamate and opioid, which may provide novel insights into pathophysiological processes and guide new therapeutic targets.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111237"},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073927","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":"O-GlcNAc transferase mediates O-GlcNAcylation of NLRP3 regulates pyroptosis in spinal cord injury","authors":"Zhichao Zeng,&nbsp;Xuqiang Liao,&nbsp;Xinjian Zhao","doi":"10.1016/j.brainresbull.2025.111233","DOIUrl":"10.1016/j.brainresbull.2025.111233","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) represents a severe disorder of the nervous system, imposing significant physical, psychological, and socioeconomic burdens on affected individuals and society.</div></div><div><h3>Objective</h3><div>We investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating pyroptosis related proteins at the posttranslational level.</div></div><div><h3>Materials and methods</h3><div>PC12 cells were stimulated with lipopolysaccharide (LPS). The O-GlcNAcylation pathway was modified by manipulating the expression of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Pro-inflammatory cytokine levels and cell pyroptosis were assessed. Co-immunoprecipitation (Co-IP) assays were employed to investigate the interaction between NLRP3 and OGT. For <em>in vivo</em> studies, an established SCI rat model was utilized. Levels of pro-inflammatory factors, NLRP3 inflammasome components, and proteins associated with pyroptosis were measured.</div></div><div><h3>Results</h3><div>Both O-GlcNAc levels and OGT expression were significantly elevated in the SCI model cells. Inhibition of OGT led to a marked reduction in the levels of pro-inflammatory cytokines and a suppression of pyroptosis. Furthermore, inhibition of OGT resulted in downregulation of NLRP3 and its O-GlcNAcylation, while overexpression of OGT produced the opposite effect. We verified the endogenous and exogenous interactions between NLRP3 and OGT. Importantly, knockout of OGT mitigated the progression of SCI in an animal model, suggesting a protective role of OGT inhibition in SCI.</div></div><div><h3>Discussion and conclusion</h3><div>This study preliminarily proved that the mechanism of OGT mediated O-GlcNAcylation of NLRP3 participates in the action of pyroptosis in SCI. Targeting OGT and NLRP3 may be novel therapy method in SCI.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111233"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073963","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":"LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease","authors":"Lu Han ,&nbsp;Chuansheng Zhao ,&nbsp;Feng Jin ,&nbsp;Rongfeng Jiang ,&nbsp;Hao Wu","doi":"10.1016/j.brainresbull.2025.111224","DOIUrl":"10.1016/j.brainresbull.2025.111224","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is the second most common neurodegenerative disease. Long non-coding RNAs (lncRNAs) are closely linked to the occurrence and development of neurodegenerative diseases, while the underlying mechanisms remain elusive. The goal of the present study was to elucidate the mechanism by which LINC02282, a significantly downregulated lncRNA in the GEO database, elicits neuroprotective effects on PD. LINC02282 was poorly expressed in SH-SY5Y and SK-N-AS cells exposed to MPP⁺ and mice injected with MPTP. LINC02282 overexpression plasmids inhibited apoptosis and promoted the proliferation of SH-SY5Y and SK-N-AS cells. In addition, LINC02282 overexpression using an adeno-associated virus reduced neuronal damage in PD mice. LINC02282 was mainly localized in the nucleus, and LINC02282 promoted the methylation of the tripartite motif-containing protein 6 (TRIM6) promoter to inhibit TRIM6 expression. LINC02282 bound to DNA methyltransferases (DNMTs) and LINC02282 overexpression increased the binding of DNMTs to the TRIM6 promoter. Overexpression of TRIM6 alone induced PD-like symptoms in mice and combined TRIM6 upregulation inhibited the neuroprotective effect of LINC02282 both <em>in vitro</em> and <em>in vivo</em>. In summary, LINC02282 alleviated neuronal injury in PD by recruiting DNMTs to the promoter region of TRIM6 and inhibiting TRIM6 expression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111224"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073931","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 possible therapeutic role of advanced glycation end-product inhibitors in ischemic stroke","authors":"Nada H. Aljarba ,&nbsp;Hayder M. Al-Kuraishy ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Mustafa M. Shokr ,&nbsp;Marios Papadakis ,&nbsp;Athanasios Alexiou ,&nbsp;Mubarak Alruwaili ,&nbsp;Mohammed Alrouji ,&nbsp;Mohammed S. Alshammari ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.brainresbull.2025.111236","DOIUrl":"10.1016/j.brainresbull.2025.111236","url":null,"abstract":"<div><div>The advanced glycation end-products (AGEs) are toxic molecules result from non-enzymatic interactions of sugar with lipids or proteins. AGEs promote the generation of reactive oxygen species that induce the release of pro-inflammatory cytokines, and alter the intracellular signaling leading to progressive biochemical and metabolic derangements. AGEs-induced cellular aging is implicated in the development and progression of different neurological disorders such as dementia, neuropsychiatric disorders, and cerebrovascular diseases. Particularly, AGEs-induced microangiopathy and macroangiopathy trigger the induction of prothrombotic/thrombotic cascades with subsequent increase risk of acute ischemic stroke (AIS). Many studies highlighted that AGEs serum levels are correlated with the incidence, pathogenicity, and severity of AIS. However, the relationship between AGEs and AIS is not elucidated completely. Therefore, this review aims to discuss how AGEs promote the development and progression of AIS, and how AGEs inhibitors could be effective in the management of AIS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111236"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073964","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":"CD8+T cells and monocytes were associated with brain alterations in human immunodeficiency virus-infected individuals with cognitive impairment","authors":"Xin Zhang ,&nbsp;Zhen Li ,&nbsp;Jiahao Ji ,&nbsp;Yundong Ma ,&nbsp;Guangqiang Sun ,&nbsp;Xue Chen ,&nbsp;Ling Zhang ,&nbsp;Tong Zhang ,&nbsp;Yulin Zhang ,&nbsp;Yang Zhang","doi":"10.1016/j.brainresbull.2025.111231","DOIUrl":"10.1016/j.brainresbull.2025.111231","url":null,"abstract":"<div><div>Cognitive impairment (CI) continues to be a concern for people living with HIV-1 (PLWH) in the era of antiretroviral therapy (ART), yet the underlying mechanisms remain unclear. We aimed to elucidate the structural and functional brain alterations and peripheral immune profile of PLWH with CI, as well as the correlation between them. PLWH were divided into CI (n = 30) and cognitive normal (CN, n = 59) groups based on the Montreal Cognitive Assessment, and underwent multi-modal magnetic resonance imaging. Mass cytometry was utilized to profile immune cells, while the liquid chip technique was employed to measure plasma levels of cytokines and chemokines. Spearman correlation analyses were conducted for correlation analysis. Here, we found that the gray matter volume in left supramarginal gyrus was reduced, and the ReHo in the right middle frontal gyrus and the functional connectivity between right middle frontal gyrus and left postcentral gyrus were enhanced in CI group compared to CN group. Additionally, the frequencies of naïve CD8⁺T cells (Tn) and CD31lowCD8⁺ Tn were significantly correlated with gray matter volume in the left supramarginal gyrus. The amplitude of low frequency fluctuations in a specific brain region of frontal-middle lobe was negatively correlated with the frequencies of non-classical monocytes (nCM) and their subpopulations (CCR2^lownCM, CD57^lownCM and CD127⁺nCM), and positively associated with the plasma interleukin 25 and transforming growth factor-α levels. These findings suggest the association between peripheral immunity and the brain abnormalities in PLWH, highlighting a potential role of the immune-brain-cognition axis in the pathogenesis of CI in Chinese PLWH.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111231"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073928","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":"Dynamic alterations in spontaneous neural activity in patients with attention-deficit/hyperactivity disorder: A resting-state fMRI study","authors":"Rui Hu ,&nbsp;Wei Du ,&nbsp;Fan Tan ,&nbsp;Yong Wu ,&nbsp;Chun Yang ,&nbsp;Weiwei Wang ,&nbsp;Wen Chen ,&nbsp;Yanwei Miao","doi":"10.1016/j.brainresbull.2025.111230","DOIUrl":"10.1016/j.brainresbull.2025.111230","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the change of dynamic amplitude of low-frequency fluctuation (dALFF) and dynamic fractional amplitude of low-frequency fluctuation (dfALFF) in patients with attention-deficit/hyperactivity disorder (ADHD), and to explore whether dALFF/dfALFF can be used to distinguish ADHD from health controls (HCs).</div></div><div><h3>Methods</h3><div>Forty-eight cases of clinically confirmed ADHD and forty-four cases of HCs were included in the present study. It was compared to the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), as well as the dynamic indicators dALFF and dfALFF. We investigated the relationship between clinical and dynamic indicators, and additionally performed voxel-based functional connectivity (FC) analysis. Finally, we developed an auxiliary diagnosis model.</div></div><div><h3>Results</h3><div>Brain regions with increased dALFF variability of ADHD were located in right middle frontal gyrus (MFG), left inferior parietal lobe (IPL) and superior parietal gyrus (SPG) compared with HCs. Meanwhile, increased dfALFF variability was also observed in left lingual gyrus (LING), right MFG and left middle occipital gyrus (MOG) in ADHD compared to HCs. Neuropsychological scale scores correlated with some dALFF and dfALFF indicators. Reduced FC was found between the left IPL and right cerebellum crus II in ADHD compared with HCs. With dALFF and dfALFF variability as features, we achieved a good area under the curve and an accurate classification.</div></div><div><h3>Conclusion</h3><div>This study offers new valuable insights into the cerebral dysfunction associated with ADHD from the standpoint of dynamic local brain activity. The understanding of dALFF/dfALFF variability can contribute to the comprehension of neurophysiological mechanisms and potentially aid in the diagnosis of ADHD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111230"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073929","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":"Altered individual-based morphological brain network in type 2 diabetes mellitus","authors":"Wang Yan ,&nbsp;Ge Limin ,&nbsp;Sun Zhizhong ,&nbsp;Cao Zidong ,&nbsp;Qiu Shijun","doi":"10.1016/j.brainresbull.2025.111228","DOIUrl":"10.1016/j.brainresbull.2025.111228","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is recognized as a risk factor for cognitive decline, potentially linked to disrupted network connectivity. However, few previous studies have examined individual-based morphological brain networks in T2DM and their association with clinical characteristics. In our study, we enrolled 123 patients with T2DM and 91 healthy controls (HC). We constructed the networks using symmetric Kullback–Leibler (KL) divergence-based similarity (KLS) and calculated various global and nodal metrics based on graph theory to describe the topological properties of the networks. Firstly, T2DM exhibited increased nodal degree in the left para-hippocampus, left amygdala, left precuneus, bilateral putamen, and right inferior temporal gyrus, and the concentrations of glycosylated hemoglobin (HbA1c) were positively correlated with the nodal degree of the left precuneus. Secondly, we identified hypo-connected and hyper-connected subnetworks, primarily involved with reward circuits and attention network, respectively. Lastly, altered morphological connectivity (MC) was linked to cognitive performance, and the aforementioned subnetworks may serve as predictors of cognitive performance. In conclusion, this study provided neuroimaging evidence for understanding cognitive changes by analyzing the properties and connections of individual-based morphological brain networks (MBNs) in T2DM patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111228"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073926","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 regulates ferroptosis to improve postoperative cognitive dysfunction in mice through mediating GRX1/GSK-3β/Nrf2 axis","authors":"Xiaqing Zhang,&nbsp;Afen Zhang,&nbsp;Rui Li,&nbsp;Mingna Jiao,&nbsp;Rou Wen,&nbsp;Rongzhi Zheng","doi":"10.1016/j.brainresbull.2025.111234","DOIUrl":"10.1016/j.brainresbull.2025.111234","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of postoperative cognitive dysfunction (POCD) is higher happening in the elderly. It has been reported electroacupuncture (EA) was beneficial to the treatment of POCD, but its specific regulatory mechanism is still unclear.</div></div><div><h3>Methods</h3><div>Through partial hepatectomy in mice, POCD model of mice was established. Baihui acupoint (GV20) was selected for targeted point of EA therapy. Morris water maze (MWM) was applied to evaluate cognitive impairment of mice. HE staining was used to examine cell arrangement and cell morphology in hippocampus of mice. RT-qPCR, western blot and IHC were employed to detect abundance of genes and proteins. MDA, GSH and iron levels was measured by some commercial kits.</div></div><div><h3>Results</h3><div>Our findings revealed that partial hepatectomy surgery impaired learning and memory ability of mice, promoted ferroptosis. inhibited GRX1 and inactivated GSK-3β/Nrf2 pathway. However, EA therapy abolished these effects. In addition, GRX1 silencing and erastin abolished EA-mediated alterations of improving POCD in mice.</div></div><div><h3>Conclusion</h3><div>EA suppressed ferroptosis by regulating GRX1/GSK-3β/Nrf2 pathway to improve postoperative cognitive dysfunction of POCD mice.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111234"},"PeriodicalIF":3.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073930","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":"Bisdemethoxycurcumin mitigates traumatic brain injury in rats by modulating autophagy and oxidative stress via heat shock protein 90 alpha family class A member 1-mediated nuclear translocation of transcription factor EB","authors":"Yan Xu,&nbsp;Liang-Shan Peng,&nbsp;Chao-Qun Xiao,&nbsp;Yi Zhou,&nbsp;Qiao-Sheng Wang,&nbsp;Hui Fu","doi":"10.1016/j.brainresbull.2025.111221","DOIUrl":"10.1016/j.brainresbull.2025.111221","url":null,"abstract":"<div><h3>Background</h3><div>Bisdemethoxycurcumin (BDMC), the primary active compound found in turmeric, exhibits diverse pharmacological properties. The study aimed to investigate the mechanisms underlying the protective effects of BDMC in traumatic brain injury (TBI).</div></div><div><h3>Methods</h3><div>A rat TBI model was established using the Feeney’s freefall epidural impact method, followed by BDMC treatment. Rat cortical neuron cells were exposed to hydrogen peroxide (H₂O₂) to induce oxidative stress and then treated with BDMC. The cells were also pretreated with autophagy inhibitor 3-MA and heat shock protein 90 alpha family class A member 1 (HSP90AA1) inhibitor 17-AAG. Additionally, the experiments also involved treating H₂O₂-exposed cortical neurons with 17-AAG and silencing HSP90AA1 expression. Co-immunoprecipitation was utilized to verify interactions between HSP90AA1 and transcription factor EB (TFEB), TFEB and nuclear factor erythroid 2 related factor 2 (Nrf2), and the localization of these complexes in the cytoplasm and nucleus.</div></div><div><h3>Results</h3><div>BDMC treatment significantly reduced modified neurological severity scores, brain water content, inflammatory infiltration, oxidative stress, and apoptosis in the cerebral cortex of TBI rats. Additionally, BDMC treatment elevated the expression of Beclin 1 and light chain 3 (LC3) II/LC3 I ratio while decreasing p62 expression. It also promoted TFEB nuclear translocation and increased HSP90AA1 levels in both the cytoplasm and nucleus, along with elevated nuclear Nrf2 expressions in TBI models. <em>In vitro</em> experiments showed decreased malondialdehyde levels, elevated glutathione peroxidase and superoxide dismutase levels upon BDMC treatment, along with repressed cortical neurons apoptosis, elevated Beclin 1 and LC3 II/LC3 I expressions, decreased p62 expressions, reduced cytoplasmic TFEB expression, increased nuclear TFEB and Nrf2 expression, and elevated HSP90AA1 expression in the cytoplasm and nucleus. Mechanistically, BDMC mediated autophagy and oxidative stress by activating HSP90AA1/TFEB/Nrf2 axis. Finally, HSP90AA1 was shown to regulate Nrf2 expression by binding to TFEB in the cellular model.</div></div><div><h3>Conclusions</h3><div>BDMC alleviated TBI in rats by regulating autophagy and oxidative stress through HSP90AA1-mediated nuclear translocation of TFEB.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111221"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036540","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}