Brain Research Bulletin最新文献

{"title":"Subcortical regional volume vulnerability linked to child neglect without other forms of maltreatment","authors":"Natasha Y.S. Kawata ,&nbsp;Takashi X. Fujisawa ,&nbsp;Akiko Yao ,&nbsp;Hidehiko Okazawa ,&nbsp;Akemi Tomoda","doi":"10.1016/j.brainresbull.2026.111771","DOIUrl":"10.1016/j.brainresbull.2026.111771","url":null,"abstract":"<div><div>Child neglect during critical stages of development has been associated with long-term adverse outcomes, including impairments in social, emotional, and physical health, as well as elevated risks of mental and cardiovascular disorders. This study examined whether alterations in corpus callosum (CC) morphology—essential for interhemispheric communication—are associated with the neural mechanisms underlying psychosocial characteristics in children exposed to neglect. Brain morphology was assessed using T1-weighted magnetic resonance imaging in Japanese children with a history of neglect (neglect group, <em>n</em> = 22) and compared with non-maltreated Japanese children (non-CM group, <em>n</em> = 66). Boys in the neglect group exhibited a greater volume in the middle anterior portion of the CC (CC2) than non-CM boys (<em>d</em> = 0.81, estimate = 208.38, <em>t</em> = 3.35, false discovery rate [FDR]-adjusted <em>p</em> = 0.01). Additionally, CC2 volume was positively correlated with hyperactivity-inattention scores across both sexes (<em>d</em> = 0.53, estimate = 111.68, <em>t</em> = 2.85, FDR-adjusted <em>p</em> = 0.03). These findings indicate sex-specific effects of neglect on CC development and emphasize the importance of clarifying the neurodevelopmental consequences of neglect and their associations with psychosocial functioning.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111771"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149224","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":"Electroacupuncture alleviates inflammatory pain via the activation of GABAergic inhibitory interneurons in mouse spinal dorsal horn","authors":"Jiawei Zhang ,&nbsp;Yang Bao ,&nbsp;Mengye Zhu ,&nbsp;Quan Wan ,&nbsp;Jinjin Zhang ,&nbsp;Xuezhong Cao ,&nbsp;Huan Zou ,&nbsp;Qinghua Yin ,&nbsp;Ziming Chen ,&nbsp;Gang Xu ,&nbsp;Xuexue Zhang ,&nbsp;Daying Zhang ,&nbsp;Tao Liu ,&nbsp;Yong Zhang","doi":"10.1016/j.brainresbull.2026.111741","DOIUrl":"10.1016/j.brainresbull.2026.111741","url":null,"abstract":"<div><div>Electroacupuncture (EA), a modern adaptation of traditional acupuncture, has shown promising analgesic effects across various pain models. However, the underlying central mechanisms remain insufficiently characterized. The dorsal horn of the spinal cord serves as a critical hub for the transmission and modulation of nociceptive signals. Increasing evidence suggests that spinal disinhibition, primarily resulting from impaired excitability of inhibitory interneurons and diminished synthesis or release γ-aminobutyric acid (GABA) and glycine, accounts for the development and maintenance of pain. In this study, we investigated whether EA alleviates inflammatory pain by modulating the activity of GABAergic inhibitory interneurons in the superficial dorsal horn of the spinal cord. A murine model of inflammatory pain was established by subcutaneous injection of complete Freund's adjuvant (CFA) into the hind paw. EA was applied at the Huantiao (GB30) and Yanglingquan (GB34) acupoints on alternate days following CFA injection. Mechanical hypersensitivity was assessed by paw withdrawal threshold. Neuronal activity was evaluated using immunofluorescence staining for c-fos, Lmx1b, Pax2, and GABA. Furthermore, whole-cell patch-clamp recordings were conducted on spinal slices from GAD67-GFP transgenic mice to assess the electrophysiological properties of GABAergic interneurons. EA significantly attenuated mechanical hypersensitivity in CFA-treated mice without affecting locomotor function. Immunofluorescence staining revealed that EA enhanced c-fos expression in the dorsal horn during early stages of treatment, reduced the proportion of c-fos-positive excitatory (Lmx1b-positive) neurons, and markedly increased the activation of inhibitory (Pax2-positive and GABA-positive) interneurons. In addition, electrophysiological recordings demonstrated that EA significantly depolarized the resting membrane potential and increased the firing frequency of GAD67-GFP-positive inhibitory interneurons in the CFA + EA group compared to the CFA group. Collectively, our results suggest EA at Huantiao and Yanglingquan acupoints could relieve inflammatory pain, potentially through enhancing of the excitability and activity of GABAergic inhibitory interneurons in the spinal dorsal horn. This study provides novel mechanistic insight into spinal modulation of nociceptive processing by EA and supports its therapeutic promise for inflammatory pain management.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111741"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028503","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":"Niosome-encapsulated sodium butyrate enhances blood-brain barrier integrity and reduces neuroinflammation in a rat model of ischemic stroke","authors":"Nasim Naseri ,&nbsp;Mohammad Reza Bigdeli ,&nbsp;Fatemeh Mortazavi Moghadam ,&nbsp;Bahram Kazemi","doi":"10.1016/j.brainresbull.2026.111736","DOIUrl":"10.1016/j.brainresbull.2026.111736","url":null,"abstract":"<div><div>Ischemic stroke remains a major cause of mortality and disability worldwide, accompanied by severe inflammation and blood-brain barrier (BBB) disruption. Sodium butyrate (SB), a promising therapeutic agent, has been extensively studied for its anti-inflammatory effects in neurological disorders. However, its bioavailability is limited by low bioavailability and a short half-life. To address this challenge, SB-loaded niosome nanoparticles (NSB) were synthesized using the thin-film hydration method with a 1:1 ratio of Tween-60 and cholesterol and tested for physicochemical properties. NSB exhibited a particle size of 81.59 nm, PDI of 0.276, zeta potential of –3.36 mV, entrapment efficiency of 94.11 %, and 62.7 % reduction in cumulative release over 24 h. Also, Field-emission scanning electron microscopy (FE-SEM) confirmed the spherical morphology and polydispersity of the nanoparticles. To investigate the therapeutic efficacy of NSB, male Wistar rats were divided into four groups: sham, control, SB, and NSB. Treatments were administered intraperitoneally, followed by middle cerebral artery occlusion (MCAO). Neurobehavioral assessments, histopathological alterations, BBB permeability, biochemical factors, and relative mRNA expression of <em>Tnf-α</em>, <em>Il-1β</em>, <em>Claudin-5</em>, <em>Zo-1</em>, and <em>Mmp-9</em> were measured 24 h post-reperfusion. NSB administration significantly reduced infarct volume, neurobehavioral deficits, BBB permeability, and histopathological damage compared to free SB. Additionally, NSB increased the enzyme activity of superoxide dismutase and glutathione peroxidase, and decreased malondialdehyde levels and mRNA expression of proinflammatory cytokines. Furthermore, NSB preserved BBB integrity by reducing <em>Mmp-9</em> expression while upregulating <em>Claudin-5</em> and <em>Zo-1</em>. These findings suggest niosomes as a promising nano-formulation to enhance SB bioavailability and neuroprotective efficacy in ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111736"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994219","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":"CircHIPK3 regulates TGF-β1/smad3 signaling in communicating hydrocephalus after intraventricular hemorrhage by sponging miR-30a-3p via ACT1","authors":"Yexin Yuan ,&nbsp;Qian Ouyang ,&nbsp;Yijian Yang ,&nbsp;Junqiang Wang ,&nbsp;Kaiyue Wang ,&nbsp;Peng Long ,&nbsp;Yifeng Chen ,&nbsp;Zhikun Liu ,&nbsp;Zhiping Zhang ,&nbsp;Zhangjie Su ,&nbsp;Gelei Xiao","doi":"10.1016/j.brainresbull.2026.111751","DOIUrl":"10.1016/j.brainresbull.2026.111751","url":null,"abstract":"<div><div>While circRNAs have been demonstrated to play critical roles in various neurological disorders, their functional mechanisms in post-intraventricular hemorrhage (IVH) communicating hydrocephalus remain poorly understood. Here we report a circular RNA, circular RNA homeodomain interacting protein kinase 3 (circHIPK3), significantly upregulated in meningeal tissues of IVH rat models. Knockdown of circHIPK3 markedly attenuated meningeal fibrosis, reduced ventricular dilation, and improved neurological function in IVH rats. Using both IVH rat models and thrombin-induced astrocyte cell lines, we validated the functional role of circHIPK3 in the pathogenesis of IVH-induced communicating hydrocephalus. Mechanistically, circHIPK3 functions as an endogenous sponge of miR-30a-3p to decrease its activity, resulting in upregulation of ACT1(TRAF3IP2) expression, which in turn triggers TGF-β1/Smad3 signaling pathway activation, ultimately driving fibrotic progression after IVH. Collectively, our findings suggest that circHIPK3 and its coupling mechanism are implicated in IVH, providing compelling evidence that circHIPK3 could be a key therapeutic target against post-IVH communicating hydrocephalus.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111751"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090260","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":"Saraswata Ghrita mitigates AlCl₃- and D-galactose–induced cognitive deficits in a murine Alzheimer’s-like model: In silico and in vivo insights","authors":"Robin Badal ,&nbsp;Balveer Kaur ,&nbsp;Harvinder Singh ,&nbsp;Poonam Sharma ,&nbsp;Pramod Yadav ,&nbsp;Arun Mahapatra ,&nbsp;Shivani Ghildiyal ,&nbsp;Ashok Kumar Patel ,&nbsp;Lalan Kumar ,&nbsp;Bhupesh Sharma ,&nbsp;Pradeep Kumar Prajapati ,&nbsp;Tanuja Nesari","doi":"10.1016/j.brainresbull.2026.111742","DOIUrl":"10.1016/j.brainresbull.2026.111742","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is characterized by cognitive decline linked to cholinergic dysfunction, oxidative stress, and neuroinflammation. Saraswata Ghrita (SG), a classical Ayurvedic formulation, was evaluated using an integrated in silico–in vivo workflow focusing on acetylcholinesterase (AChE) and related pathways.</div></div><div><h3>Methods</h3><div>SG constituents were profiled by GC–MS/MS and HR-LCMS/MS-QTOF. BBB-permeable, drug-like candidates were prioritized (SwissADME/BOILED-Egg) and evaluated by docking and molecular dynamics. In vivo, mice received AlCl₃ (4 mg/kg, i.p.) + <span>D</span>-galactose (50 mg/kg, i.p.) for 60 days; SG (3, 6, 12 mL/kg, p.o.) or donepezil (0.5 mg/kg, i.p.) was administered on days 31–60. Behavioral, biochemical, and histological endpoints were assessed (n = 6/group).</div></div><div><h3>Results</h3><div>In silico, LIG_91 showed the top predicted AChE binding affinity (−8.5 kcal·mol⁻¹) and LIG_212 scored −7.8 kcal·mol⁻¹ (supportive evidence). AlCl₃+<span>D</span>-galactose impaired cognition (MWM day-4 ELT 85.8 ± 5.3 s; TSTQ 34.6 ± 2.2 s). SG 12 mL/kg improved MWM performance (ELT 44.1 ± 3.2 s, ∼49 % lower vs model; TSTQ 50.1 ± 2.8 s, ∼45 %higher), while donepezil produced greater improvement (ELT 26.7 ± 2.4 s, ∼69 % lower; TSTQ 58.1 ± 5.4 s, ∼68 %higher). SG 12 mL/kg reduced oxidative stress (TBARS 12.93 ± 1.58 → 8.84 ± 0.52 nM/mg, ∼32 % decrease) and improved antioxidant status (GSH 7.52 ± 0.48 → 11.10 ± 0.48 µM/mg, ∼48 % increase). SG also attenuated neuroinflammation (IL-6 211.1 ± 10.6 → 165.0 ± 23.6 pg/mL, ∼22 % decrease; TNF-α 179.3 ± 8.7 → 133.7 ± 7.8 pg/mL, ∼25 % decrease; IL-10 12.3 ± 1.0 → 30.2 ± 5.2 pg/mL, ∼146 % increase) and lowered AChE activity (10.61 ± 0.61 → 8.49 ± 0.49 µM/min/mg, ∼20 % decrease). H&amp;E micrographs qualitatively suggested reduced cortical neuronal degeneration.</div></div><div><h3>Conclusions</h3><div>SG administration was associated with improved cognition and partial normalization of cholinergic, oxidative, and inflammatory markers in this model. Computational findings support possible AChE engagement but are not definitive; further quantitative histology and standardized-formulation studies are warranted.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111742"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040396","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":"Altered brain dynamic in cirrhotic patients without overt hepatic encephalopathy: State and trait features","authors":"Chao Ju ,&nbsp;Longtao Yang ,&nbsp;Zhongshang Dai ,&nbsp;Yisong Wang ,&nbsp;Yingxia Zhou ,&nbsp;Jun Liu","doi":"10.1016/j.brainresbull.2026.111724","DOIUrl":"10.1016/j.brainresbull.2026.111724","url":null,"abstract":"<div><div>Neurocognitive impairment, a prevalent complication in cirrhosis, correlates with disruptions in static functional connectivity(FC) of the brain. This study aims to explore altered spatiotemporal properties of blood oxygen-level dependent(BOLD) signals and elucidate their association with neurocognitive changes in cirrhotic patients. Between March 2023 and February 2025, we recruited 77 cirrhotic patients and 66 healthy controls(HCs) accompanied by resting-state functional magnetic resonance imaging(rs-fMRI) acquisition. Neurocognitive function was evaluated by psychometric hepatic encephalopathy score(PHES). The hidden Markov model(HMM) was used to explain variations in rs-fMRI averaged functional activity(AFA) and FC across the whole-brain by using a set of 5 unique recurring states. This study assessed the stability between different groups by comparing the time spent in each state and the mean duration of visits to each state. Mann<img>Whitney U tests, Kruskal Wallis H test, chi-squared test, correlation analysis. After Bonferroni correction, cirrhotic patients with minimal hepatic encephalopathy(MHE) showed significantly higher temporal stability and proportional time spent in state#1 characterized by lower AFA of frontoparietal network(FPN) and subcortical network and higher AFA of visual network (VN), as well as have lower fractional occupancy(FO) and averaged lifetime(ALT) in state#5, which is characterized by weaker within-network FC and lower AFA of limbic network(LN), salience network(SN), somatosensory motor network(SMN), and default mode network(DMN). We observed a significant positive correlation(Bonferroni corrected) between dynamic properties in state#5 and PHES performance. These findings suggest that disrupted brain functional synchrony across time is present in MHE and is linked to cognitive impairment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111724"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951553","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":"Purα overexpression mitigates neonatal hypoxic-ischemic brain damage by inhibiting neuronal pyroptosis via the P2X7R/NLRP3/Caspase-1 pathway","authors":"Da Zheng ,&nbsp;Hui Zhang ,&nbsp;Yi-Kai Zou ,&nbsp;Jiao-Yang Yang ,&nbsp;Shu-Yi He ,&nbsp;Hai-Jing Peng ,&nbsp;Jian-Xia Liu ,&nbsp;Shao-Hua Qi ,&nbsp;Jia-Wei Min","doi":"10.1016/j.brainresbull.2026.111726","DOIUrl":"10.1016/j.brainresbull.2026.111726","url":null,"abstract":"<div><div>Hypoxic-ischemic brain damage (HIBD) is a common neonatal disorder that often leads to permanent neurological sequelae. Neuronal pyroptosis, a pro-inflammatory form of programmed cell death, has been increasingly recognized as a key contributor to neuronal damage and subsequent neurological deficits in HIBD. However, effective therapeutic strategies for HIBD remain limited, highlighting the urgent need to identify novel therapeutic targets. Purine-rich element-binding protein α (Purα) is a multifunctional DNA/RNA-binding protein involved in gene transcription and nervous system regulation. However, its role in neonatal HIBD has not been defined. Here, we investigated the neuroprotective effects of Purα in both <em>in vivo</em> and <em>in vitro</em> models of HIBD. We found that endogenous Purα protein levels were markedly reduced in brain tissue from HI-challenged neonatal mice and in primary cortical neurons subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Purα overexpression effectively reduced cerebral infarction, alleviated neuronal injury, attenuated brain atrophy, and improved neurological outcomes in neonatal HIBD mice. In cultured neurons, Purα overexpression significantly increased cell viability and reduced cell death following OGD/R. RNA sequencing identified purinergic 2X7 receptor (P2X7R) as a potential downstream target of Purα, consistent with P2X7R’s established role in pyroptosis regulation. Mechanistic studies further demonstrated that Purα overexpression suppressed P2X7R expression and inhibited activation of the NLRP3/Caspase-1 pathway, as indicated by reduced levels of P2X7R, NLRP3, Caspase-1, cleaved Caspase-1, GSDMD-N, and IL-1β. Collectively, these findings reveal a novel role for Purα in mitigating neuronal pyroptosis via regulation of the P2X7R/NLRP3/Caspase-1 pathway and support Purα as a promising therapeutic target for neonatal HIBD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111726"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976336","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":"MAF1 loss protects against ischemic cerebral injury by attenuating NLRP3-mediated pyroptosis","authors":"Xue Gao,&nbsp;Hanzhi Wang,&nbsp;Lingting Jin,&nbsp;Shumeng Li,&nbsp;Gang Li,&nbsp;Can Cui,&nbsp;Yingying Han","doi":"10.1016/j.brainresbull.2026.111732","DOIUrl":"10.1016/j.brainresbull.2026.111732","url":null,"abstract":"<div><h3>Background</h3><div>Acute ischemic stroke (AIS) is the second leading cause of death worldwide and is associated with high rates of disability and mortality. Emerging evidence indicates that the transcriptional regulator MAF1 may play an important role in neurological diseases by modulating the NLRP3 signaling pathway. Previous studies suggest the transcriptional regulator MAF1 may play an important role in neurological diseases through regulating NLRP3 pathway. However, its role in ischemic cerebral injury remains unclear. This study aims to reveal the key role and mechanisms of MAF1 in AIS.</div></div><div><h3>Methods</h3><div>Using transient middle cerebral artery occlusion (tMCAO) model, the sensorimotor function of mice after modeling was evaluated by behavioral methods and changes of MAF1 expression were investigated by Polymerase Chain Reaction (PCR), Western blot and Immunofluorescence (IF) staining. The oxygen glucose deprivation/reperfusion (OGD/R) model was used as cell model for in vitro verification. Stereotactic injection of AAV-hsyn-shMAF1 was used to assess the effect of MAF1 knockdown on the improvement of neurological function and infarct volume in stroke mice. RNA sequencing was performed to identify differentially expressed genes between OGD/R-Lenti-shMAF1 and OGD/R-Lenti-SCR groups. Western blot analysis was further applied to examine molecular alterations in the downstream NLRP3 pathway.</div></div><div><h3>Results</h3><div>Expression of the transcription factor MAF1 was upregulated in AIS and conditional Conditional knockdown of MAF1 in the tMCAO mouse model alleviated neurological deficits and reduced infarct volume. RNA sequencing revealed altered expression of NLRP3-related pyroptosis proteins and pathways following MAF1 knockdown in OGD/R-treated primary neurons. Downregulation of MAF1 led to expression changes of NLRP3 inflammasome/pyroptosis pathways in both tMCAO mouse and OGD/R cell models.</div></div><div><h3>Conclusions</h3><div>MAF1 expression was significantly increased in animal and cellular models of AIS. Knockdown of MAF1 improved neurological function after AIS and the protective effect is related to the regulation of the NLRP3 inflammasome/pyroptosis pathway. These findings elucidated a critical role and mechanistic insight for MAF1 in AIS pathogenesis, highlighting its potential as a therapeutic target for ischemic stroke treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111732"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975644","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":"TCF7L2 transcriptionally regulates C1QB to exacerbate synaptic pruning-dependent neuronal injury in the epileptic hippocampus","authors":"Lulu Wu ,&nbsp;Yuping Huang ,&nbsp;Xinyu Wang ,&nbsp;Ting Tian ,&nbsp;Dandan Feng ,&nbsp;Guoping Zhou","doi":"10.1016/j.brainresbull.2026.111730","DOIUrl":"10.1016/j.brainresbull.2026.111730","url":null,"abstract":"<div><div>Epilepsy represents one of the most prevalent and debilitating chronic neurological disorders. While the complement component 1q subcomponent B (C1QB) has been implicated in synaptic pruning and is associated with various neurological diseases, including epilepsy, the transcriptional regulatory mechanisms of the <em>C1QB</em> gene in epilepsy remain poorly understood. Here, we identified transcription factor 7-like 2 (<em>TCF7L2</em>) as a novel upstream transcriptional regulator of <em>C1QB</em> gene. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays confirmed the direct binding of <em>TCF7L2</em> to the <em>C1QB</em> promoter region and its positive regulatory effect on <em>C1QB</em> expression in vitro. Using a kainic acid-induced epilepsy model in male C57BL/6 mice, we demonstrated a significant upregulation of both <em>Tcf7l2</em> and <em>C1qb</em> in the hippocampal region, which was accompanied by microglial activation and neuronal damage. Notably, the lentivirus-mediated specific knockdown of <em>Tcf7l2</em> effectively reversed the overexpression of <em>C1qb</em>, attenuated microglial activation, and ameliorated neuronal injury in epileptic mice. Our study establishes the <em>TCF7L2-C1QB</em> regulatory axis and demonstrates its pathogenic role in epilepsy, suggesting that targeting this pathway may offer a novel therapeutic strategy for epilepsy treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111730"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975646","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":"Alkaloids and flavonoids of Solanaceae: Mechanisms of action in neurodegenerative diseases","authors":"Qiushi Yin ,&nbsp;Mingzhen Hu ,&nbsp;Wei Li ,&nbsp;Peng Cheng ,&nbsp;Yuqing Liu ,&nbsp;Long Liu ,&nbsp;Lin Chen ,&nbsp;Qin Ru ,&nbsp;Yuxiang Wu","doi":"10.1016/j.brainresbull.2026.111716","DOIUrl":"10.1016/j.brainresbull.2026.111716","url":null,"abstract":"<div><div>Neurodegenerative diseases (e.g., Alzheimer's disease [AD], Parkinson's disease [PD], Huntington's disease [HD]) pose a serious threat to human health. Current therapeutic approaches have limitations such as significant side effects and limited efficacy, making natural plant active ingredients an emerging research focus in this field. Solanaceae plants are widely distributed worldwide, rich in secondary metabolites such as alkaloids and flavonoids, and have long been used in traditional medicine. This review systematically summarizes the structural characteristics of Solanaceae-derived alkaloids (e.g., nicotine[NI], atropine[ATP], scopolamine[SCO]) and flavonoids (e.g., quercetin[QR], luteolin[LUT], kaempferol[KAE], anthocyanidin[ACN]), as well as their therapeutic potential and core mechanisms of action against the three major neurodegenerative diseases — including multi-target regulatory pathways such as antioxidative stress, inhibiting neuroinflammation, regulating neurotransmitter balance, preventing abnormal protein aggregation, and suppressing neuronal apoptosis. Additionally, this review analyzes the challenges faced by these natural products in extraction and purification, bioavailability, target selectivity, and clinical translation, and prospects the potential of promoting their clinical application through technological breakthroughs such as synthetic biology and nanodelivery systems. This review indicates that Solanaceae-derived secondary metabolites provide an important resource for the development of safe and effective therapeutic drugs for neurodegenerative diseases, with broad application value.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111716"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976335","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}