Neuroreport最新文献

{"title":"Methyltransferase-like 14 alleviates neuronal ferroptosis in Alzheimer's disease by regulating the peroxiredoxin 6/apoptosis signal-regulating kinase 1 signaling pathway.","authors":"Minghui Zheng, Bingxu Hou, Ruxue Ma, Zheng Tan","doi":"10.1097/WNR.0000000000002282","DOIUrl":"10.1097/WNR.0000000000002282","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease is a neurodegenerative disorder, in which ferroptosis contributes to its pathogenesis and progression. This study explored the precise mechanisms of ferroptosis in the pathological development of Alzheimer's disease.</p><p><strong>Methods: </strong>Amyloid beta 1-42 oligomer-treated SH-SY5Y cells were used to simulate Alzheimer's disease in vitro. Ferroptosis was evaluated by detecting the levels of reactive oxygen species (ROS), malonaldehyde, glutathione, Fe2+, and ferroptosis-related proteins. Cell viability was assessed by a Cell Counting Kit-8 assay. Total RNA N6-methyladenosine (m6A) levels were detected using an RNA methylation quantification kit, and peroxiredoxin 6 (PRDX6) m6A levels were analyzed by m6A RNA immunoprecipitation. The binding of methyltransferase-like 14 (METTL14) to PRDX6 was investigated by a dual-luciferase reporter assay.</p><p><strong>Results: </strong>METTL14 levels were decreased in the serum of Alzheimer's disease patients and in an in-vitro model of Alzheimer's disease, and serum levels correlated with the degree of cognitive impairment. METTL14 overexpression significantly inhibited amyloid beta 1-42 oligomer-induced ferroptosis and cytotoxicity in SH-SY5Y cells. Mechanistically, METTL14-mediated m6A modification increased PRDX6 mRNA stability, which inactivated the ROS-apoptosis signal-regulating kinase 1/p38 pathway. Rescue experiments demonstrated that PRDX6 overexpression reversed sh-METTL14-induced ferroptosis and neurotoxicity.</p><p><strong>Conclusion: </strong>METTL14 suppressed neuronal ferroptosis to delay Alzheimer's disease progression through m6A modification of PRDX6 to inactivate the ROS-apoptosis signal-regulating kinase 1/p38 pathway. Our observations provide a potential therapeutic strategy for Alzheimer's disease.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"37 11","pages":"430-441"},"PeriodicalIF":2.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC01128 alleviates neuronal injury and neurological deficits after ischemic stroke via targeting miR-92a-3p.","authors":"Jing Xiao, Jianjian Zhu","doi":"10.1097/WNR.0000000000002274","DOIUrl":"10.1097/WNR.0000000000002274","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a severe cerebrovascular disease. Focusing on ischemic stroke, this study aims to determine LINC01128 expression changes and its mechanism involving miR-92a-3p regulation.</p><p><strong>Methods: </strong>A rat model of middle cerebral artery occlusion and an oxygen-glucose deprivation/reoxygenation model of SH-SY5Y cells were established to simulate ischemic stroke. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of LINC01128 and miR-92a-3p. Dual luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down experiments were used to verify the molecular interactions. ELISA and reactive oxygen species (ROS) assays were used to evaluate the levels of inflammation and oxidative stress. The neurological function was evaluated by foot fault test, corner test, and modified neurological severity score.</p><p><strong>Results: </strong>LINC01128 expression was markedly decreased, whereas miR-92a-3p expression was increased in ischemic stroke models. Experiments confirmed that LINC01128 directly binds to miR-92a-3p. In-vivo models demonstrated that LINC01128 overexpression effectively reduced proinflammatory factor levels and ROS production, increased the anti-inflammatory factor, and improved neurological dysfunction. Overexpression of LINC01128 also mitigated oxygen-glucose deprivation/reoxygenation-induced apoptosis, inflammation, and intracellular ROS accumulation while enhancing cell viability. However, all these protective effects were reversed by co-overexpression of miR-92a-3p.</p><p><strong>Conclusion: </strong>LINC01128 exerts a crucial neuroprotective effect in ischemic stroke models by targeting miR-92a-3p, effectively alleviating neuroinflammation and oxidative stress damage while improving neurological deficits. The discovery of the LINC01128/miR-92a-3p regulatory axis provides new insights into the molecular mechanisms underlying poststroke neural injury.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"37 11","pages":"393-401"},"PeriodicalIF":2.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanol increases γ-aminobutyric acid release in the tuberomammillary nucleus but not in the prefrontal cortex in rats.","authors":"Zhangqing Ma, Wenjing Cao, Junxiu Zhang, Zongyuan Hong","doi":"10.1097/WNR.0000000000002276","DOIUrl":"10.1097/WNR.0000000000002276","url":null,"abstract":"<p><strong>Background: </strong>γ-Aminobutyric acid (GABA) is essential for the central sedative/hypnotic actions of ethanol. The tuberomammillary nucleus (TMN), the exclusive source of forebrain histaminergic innervation, functions as the principal arousal controller. Nevertheless, direct demonstration that ethanol modulates GABA release within the TMN remains elusive.</p><p><strong>Methods: </strong>In-vivo microdialysis was used to harvest dialysate from the prefrontal cortex (PFC) and TMN of anesthetized rats after systemic ethanol administration. GABA levels in the dialysate were quantified by HPLC with fluorometric detection.</p><p><strong>Results: </strong>Within the dose range of 1.5-2.5 g/kg, ethanol (intraperitoneally) did not significantly affect GABA release in the PFC during the 4-h postinjection period (P > 0.05). In contrast, the TMN exhibited a rapid, dose-dependent, and sustained increase in GABA release. The peak GABA release reached 139, 147, and 165% of the baseline level following treatment with 1.5, 2.0, and 2.5 g/kg ethanol, respectively, with the increase persisting until the end of the 4-h observation period at the 2.5 g/kg dose. During the first 2 h after injection, the total amounts of GABA released in the TMN for the three doses of ethanol were 1.16 ± 0.11, 1.94 ± 0.27, and 3.73 ± 0.46 pmol, which were significantly greater than those in the saline control group (0.69 ± 0.08 pmol, P < 0.05 or P < 0.01).</p><p><strong>Conclusion: </strong>Ethanol selectively augments GABAergic output in the TMN while leaving the PFC release unchanged, indicating that the sedative/hypnotic action of ethanol is mediated, at least partially, by enhanced GABA release confined to the TMN.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"37 10","pages":"376-381"},"PeriodicalIF":2.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ergothioneine exerts neuroprotection in experimental ischemic stroke via activation of PI3K/Akt/Nrf2 pathway.","authors":"Xizhong Jing, Lei Cai, Yalun Guan, Shuhua Liu, Yunfeng Li, Ge Li, Yongchao Li, Zhong Pei, Yifei Wang, Yu Zhang","doi":"10.1097/WNR.0000000000002273","DOIUrl":"10.1097/WNR.0000000000002273","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a leading cause of serious long-term disability and mortality worldwide. Ergothioneine (EGT), a natural dietary sulfur-containing amino acid, possesses potent antioxidant properties. This study investigates the neuroprotective potential of EGT in experimental ischemic stroke and elucidates its underlying molecular signaling pathway.</p><p><strong>Methods: </strong>Two ischemic stroke models, the photochemical ischemia model and the middle cerebral artery occlusion (MCAO) model, were established to evaluate the neuroprotective effects of EGT. 2,3,5-Triphenyltetrazolium chloride staining was performed to assess infarct volume, and laser speckle contrast imaging was used to monitor cerebral blood flow. Immunofluorescence was employed to detect the activation of astrocytes and microglia. Proteins involved in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were analyzed by Western blot to explore the underlying mechanism of EGT.</p><p><strong>Results: </strong>In both photochemical ischemia and middle cerebral artery occlusion models, EGT significantly reduced infarct volume, improved cerebral perfusion and attenuated glial cells activation. Mechanistically, EGT promoted PI3K/Akt phosphorylation, reduced cytoplasmic Kelch-like erythroid cell-derived homology-associated protein 1 expression, and enhanced nuclear Nrf2 translocation. Notably, PI3K inhibitor, LY294002, completely abolished the neuroprotective effects of EGT.</p><p><strong>Conclusion: </strong>EGT exhibits significant neuroprotection against experimental ischemic stroke by mitigating oxidative stress and neuroinflammation, and its efficacy is critically dependent on the activation of the PI3K/Akt/Nrf2 signaling pathway.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"37 10","pages":"382-392"},"PeriodicalIF":2.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond homogeneity: intrinsic connectivity of 10 primary motor cortex subregions.","authors":"Adnan A S Alahmadi","doi":"10.1097/WNR.0000000000002271","DOIUrl":"10.1097/WNR.0000000000002271","url":null,"abstract":"<p><strong>Background: </strong>The primary motor cortex [Brodmann area 4 (BA4)] is traditionally treated as a single functional region or divided into anterior and posterior components based on cytoarchitecture. However, converging evidence suggests a more complex internal functional organization.</p><p><strong>Methods: </strong>Resting-state functional MRI data were obtained from 198 healthy young adults (75 males; age range: 18-30 years) drawn from the Cambridge-Buckner dataset of the 1000 Functional Connectomes Project. Functional connectivity of Brainnetome-defined BA4 subregions was examined. Five subregions per hemisphere (A4hf, A4ul, A4ll, A4t, A4tl) were analyzed to assess (a) connectivity among BA4 subregions and (b) their integration within major large-scale functional brain networks.</p><p><strong>Results: </strong>All BA4 subregions exhibited strong and consistent coupling with sensorimotor networks, forming a conserved motor backbone. Beyond this shared architecture, subregions demonstrated distinct connectivity profiles with dorsal attention, salience, frontoparietal, visual, language, and default-mode networks, alongside structured intra-area coupling. Hemispheric asymmetries were most evident in nonmotor network interactions, particularly those related to language.</p><p><strong>Conclusion: </strong>BA4 comprises multiple functionally distinct subregions that are differentially embedded within distributed brain networks. These findings extend classical cytoarchitectonic models and provide a refined normative framework for understanding motor and nonmotor network organization within the primary motor cortex.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"37 10","pages":"368-375"},"PeriodicalIF":2.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear heme oxygenase-1 enhances blood-spinal cord barrier repair via corticotropin-releasing hormone-mediated tight junction phosphorylation.","authors":"Jin Huang, Sheng Chang","doi":"10.1097/WNR.0000000000002268","DOIUrl":"10.1097/WNR.0000000000002268","url":null,"abstract":"<p><strong>Objective: </strong>The hallmark of secondary spinal cord injury (SCI) is destruction of the blood-spinal cord barrier (BSCB). Nuclear heme oxygenase-1 (NHO-1) is involved in neuroprotection in the central nervous system. Previously, we demonstrated that adenoviral delivery of nuclear-targeted HO-1 (NHO-1) alleviates BSCB disruption, but the molecular mechanisms remain to be clarified. This study was conducted to investigate the specific regulatory mechanisms regulating tight junctions in the BSCB.</p><p><strong>Methods: </strong>A moderate T10 contusion SCI was induced in adult male Sprague-Dawley rats. Nuclear-targeted HO-1 was delivered by adenoviral pretreatment 7 days before injury. Spinal cords were collected at 24 h post-SCI for RNA-seq and quantitative real-time-PCR validation. BSCB permeability (Evans Blue), tight junction phosphorylation (western blot), and locomotor function (Basso, Beattie, and Bresnahan score and footprint analysis) were assessed, with intrathecal corticotropin-releasing hormone (CRH)-R1 agonist (Cortagine) or antagonist (Antalarmin) administered after SCI.</p><p><strong>Results: </strong>RNA-seq identified 10 overlapping differentially expressed genes across pairwise comparisons; subsequent Venn-based prioritization and quantitative real-time-PCR validation identified Crh as the most consistently regulated candidate. Functional assays demonstrated that nuclear HO-1, particularly when combined with CRH receptor activation, decreased leakage of BSCB via enhancing phosphorylation of tight junction protein which disappears after application of CRH inhibitor.</p><p><strong>Conclusion: </strong>These results indicate that nuclear-targeted HO-1 promotes BSCB repair after SCI by transcriptionally upregulating Crh and enhancing CRH-dependent phosphorylation of tight junction proteins (Claudin-5 and Occludin).</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"359-367"},"PeriodicalIF":2.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct roles of NPTX1 and NPTX2 in synaptic transmission of the fear memory engrams in the dentate gyrus.","authors":"Feihuang Mao, Yang Yang, Zhuying Jiang, Qiumin Le, Tao Jin","doi":"10.1097/WNR.0000000000002272","DOIUrl":"10.1097/WNR.0000000000002272","url":null,"abstract":"<p><strong>Background: </strong>The synaptic transmission of memory engrams is important for their roles in memory storage and retrieval, and can be regulated by multiple neuronal adhesion molecules. This study focuses on the roles of neuronal pentraxin (NPTX) family members (NPTX1 and NPTX2), which are biomarkers for cognitive decline, in the synaptic transmission of Fos-(F-RAM) and Npas4-(N-RAM)-dependent engrams formed during contextual fear conditioning in the dentate gyrus.</p><p><strong>Methods: </strong>Utilizing robust activity marking (RAM) system, contextual fear conditioning, conditional knockout (cKO) technology and electrophysiological recording, we analyzed the characteristic of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) in engram cells of wild-type and Nptxs cKO mice.</p><p><strong>Results: </strong>Nptx1 cKO leads to an increased amplitude and frequency of mEPSCs and decreased amplitude of mIPSCs in F-RAM neurons, as well as an elevated mEPSC frequency and reduced mIPSC frequency in N-RAM neurons. In contrast, Nptx2 cKO results in a decreased mEPSC frequency and increased mIPSC frequency in both F-RAM and N-RAM neurons.</p><p><strong>Conclusion: </strong>Nptx1 cKO increased engram activity while Nptx2 cKO decreased engram activity. These findings reveal the distinct roles of the NPTX family in regulating the synaptic transmission of the fear engrams.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"37 9","pages":"351-358"},"PeriodicalIF":2.1,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential dynamics of memory load: contralateral delay activity and behavioral evidence.","authors":"Mario Villena-González, Germán Campos-Arteaga, Felipe Rojas-Thomas, Juan-Pablo Morales, Vladimir López","doi":"10.1097/WNR.0000000000002270","DOIUrl":"10.1097/WNR.0000000000002270","url":null,"abstract":"<p><strong>Background: </strong>Working memory is a fundamental component of human cognition, essential for performing complex tasks that require holding and manipulating information. Visuospatial working memory (VSWM) enables the temporary retention of visual and spatial information, with its neural correlates, such as contralateral delay activity (CDA, a component of event-related potentials), providing insights into memory load dynamics. This study aimed to investigate how sequentially presented items are maintained and integrated into VSWM.</p><p><strong>Methods: </strong>Twenty-three participants performed a task where three visual items were presented sequentially, followed by a retro-cue and a test array, while accuracy and CDA were measured.</p><p><strong>Results: </strong>Behavioral results showed significant differences in accuracy across item positions, with the third item yielding the lowest accuracy. Electrophysiological findings revealed that CDA amplitude was more negative for the second item, suggesting greater cognitive resources were allocated to it compared to the first and third items. Correlations between working memory capacity, task performance, and CDA amplitudes suggest that individuals with higher working memory capacity can better adapt resource distribution to handle sequential information processing, particularly under conditions of increased cognitive load.</p><p><strong>Conclusion: </strong>These results suggest that VSWM management involves dynamic, nonuniform allocation of cognitive resources influenced by the serial position of items. These insights expand our understanding of how VSWM processes sequential inputs and may inform future studies on optimizing cognitive strategies for tasks involving complex visual and spatial information.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"37 9","pages":"341-350"},"PeriodicalIF":2.1,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic brain states and molecular signatures in primary angle-closure glaucoma.","authors":"Shui-Feng Wang, Yuan-Zhi He, Zhan-Xiang Hu, Zi-Liang Zheng, Xin Huang","doi":"10.1097/WNR.0000000000002267","DOIUrl":"10.1097/WNR.0000000000002267","url":null,"abstract":"<p><strong>Background: </strong>Primary angle-closure glaucoma (PACG) has traditionally been regarded as an ocular disorder, but accumulating evidence suggests broader central nervous system involvement. Although previous neuroimaging studies have identified static functional abnormalities, the dynamic properties of large-scale brain networks and their associated molecular signatures in PACG remain insufficiently understood.</p><p><strong>Methods: </strong>We applied Leading Eigenvector Dynamics Analysis to resting-state functional MRI data from 44 patients with PACG and 57 healthy controls to characterize recurrent whole-brain dynamic states. State-specific temporal metrics and spatial patterns were further evaluated using multiple machine learning models. To explore potential biological correlates, imaging-derived spatial patterns were linked to cortical gene expression profiles from the Allen Human Brain Atlas using partial least squares regression, followed by pathway enrichment, cell-type enrichment, and neurotransmitter receptor/transporter mapping analyses.</p><p><strong>Results: </strong>Compared with healthy controls, PACG patients showed prolonged dwell time in one recurrent dynamic state, suggesting reduced flexibility of large-scale brain dynamics. Machine learning models showed promising classification performance within the current dataset, with the most informative features primarily located in default mode network regions. Transcriptomic decoding revealed enrichment of genes related to synaptic signaling, ion channel activity, neurotransmitter transport, and neuronal communication. Cell-type enrichment analyses further implicated excitatory neurons, inhibitory neurons, and astrocytes. In addition, a significant spatial association with VMAT2 suggested that monoaminergic systems may be relevant to the observed imaging phenotype.</p><p><strong>Conclusion: </strong>PACG is associated with altered large-scale brain dynamics, particularly involving default mode network-related state instability. These imaging abnormalities show spatial associations with molecular, cellular, and neurotransmitter-related signatures.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"325-340"},"PeriodicalIF":2.1,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of ononin on cognitive and learning-memory functions in mild cognitive impairment.","authors":"Lei Yang, Wenya Zhao, Jiaojiao Zhao, Siruan Chen, Xia Qin, Zuxiao Yang, Dezhi Kong, Wei Zhang","doi":"10.1097/WNR.0000000000002264","DOIUrl":"10.1097/WNR.0000000000002264","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the potential of ononin in alleviating mild cognitive impairment (MCI) and to determine whether its effects depend on the functional recovery of neurons in the nucleus tractus solitarius (NTS).</p><p><strong>Methods: </strong>Four-month-old APP/PS1 mice were treated with 30-mg/kg ononin via oral gavage for 8 consecutive days. Cognitive behavior was assessed using the novel object recognition test, Y-maze test, and open field test. Cortical perfusion was measured by laser speckle contrast imaging. The activation of NTS neurons was detected using c-Fos immunofluorescence staining, while dendritic complexity and neuronal firing frequency were evaluated via Golgi staining and patch-clamp electrophysiology, respectively.</p><p><strong>Results: </strong>Ononin treatment significantly improved the novel object recognition index and spontaneous alternation rate in the Y-maze test in APP/PS1 mice. It also enhanced cerebral blood flow perfusion and increased the number of c-Fos-positive cells in the NTS, hippocampal CA1 region, and cortex. Furthermore, ononin increased dendritic intersections and restored dendritic spine density in NTS neurons to normal levels, along with significantly elevating their firing frequency.</p><p><strong>Conclusion: </strong>Ononin may ameliorate MCI-like cognitive deficits in APP/PS1 mice by activating NTS neurons, restoring synaptic plasticity, and improving cerebral perfusion. These findings suggest that the NTS could serve as a potential target for early intervention in Alzheimer's disease.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"308-318"},"PeriodicalIF":2.1,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}