Neurochemical Research最新文献

{"title":"Silencing PVT1 Alleviates Sevoflurane Anesthesia-Induced Oxidative Stress and Cognitive Dysfunction by Regulating miR-486-5p","authors":"Jing Qian,&nbsp;Xiaoxiao Dai,&nbsp;Zhaoxuan Li","doi":"10.1007/s11064-025-04537-1","DOIUrl":"10.1007/s11064-025-04537-1","url":null,"abstract":"<div><p>To investigate the role and mechanism of long non-coding RNA PVT1 in sevoflurane-induced oxidative stress and cognitive dysfunction. The expression level of PVT1 and the mRNA expressions of Caspase-3, Bax, and Bcl2 were detected by RT-qPCR. Cell viability and apoptosis rate were evaluated by MTT assay and flow cytometry, respectively. The levels of malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD) were determined using commercial kits. The cognitive function of rats was assessed by Morris water maze (MWM) test. Online databases were used to predict the microRNAs (miRNAs) targeted by PVT1, and dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the targeted binding relationship. PVT1 levels were significantly upregulated in hippocampal tissues of rats and HT22 cells treated with sevoflurane. Silencing of PVT1 effectively alleviated sevoflurane-induced cell apoptosis, oxidative stress, and cognitive dysfunction. Mechanistic studies showed that PVT1 targeted miR-486-5p. In sevoflurane-treated hippocampal tissues of rats and HT22 cells, inhibition of miR-486-5p counteracted the protective effects of PVT1 silencing, leading to increased cell apoptosis, exacerbated oxidative stress, and deteriorated cognitive dysfunction. PVT1 silencing mitigates oxidative stress response and cognitive dysfunction by targeting miR-486-5p, providing a novel research perspective for the treatment of sevoflurane-induced nerve injury.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028411","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 Ameliorates Neuroinflammatory Injury in CPSP Rats by Inhibiting the LncRNA MEG3-Mediated Wnt/β-Catenin Signaling Pathway","authors":"Guihua Tian,&nbsp;Meiyue Wang,&nbsp;Ke He,&nbsp;Xinyi Li,&nbsp;Yang Wu,&nbsp;Huifeng Hao,&nbsp;Fan Zhang,&nbsp;Youxiang Su,&nbsp;Junyi Long,&nbsp;Yi Lin,&nbsp;Zhihao Shang,&nbsp;Liangqing Huang","doi":"10.1007/s11064-025-04547-z","DOIUrl":"10.1007/s11064-025-04547-z","url":null,"abstract":"<div><p>Electroacupuncture (EA) therapy has been shown to significantly alleviate central poststroke pain (CPSP). However, current research on the mechanisms by which EA relieves CPSP is insufficient. This study explored the role of EA in ameliorating central nervous system inflammation in CPSP rats.The CPSP rat model was established by injecting collagenase IV into the right ventral posterolateral nucleus of the thalamus (VPL). The treatment group was treated with 15 Hz and 2 mA continuous wave EA every other day for a total of 8 sessions. The lncRNA MEG3 (MEG3) was knocked down or overexpressed by adeno-associated virus delivery in vivo in the rat brain. Pain thresholds were measured to assess the hypersensitivity of the rats to pain. Immunofluorescence, Nissl staining and enzyme-linked immunosorbent assay (ELISA) were used to assess the levels of <i>MEG3</i> and glial fibrillary acidic protein (GFAP) in VPL brain tissue, neuronal injury, and the levels of substance P (SP), TNF-α, IL-1β and IL-6 in VPL brain tissue and serum, respectively. The levels of <i>MEG3</i>, Wnt3a, β-catenin and GFAP in VPL brain tissue were assessed by qRT‒PCR or Western blotting. EA inhibits the expression of <i>MEG3</i> and neuroinflammatory injury in the VPL brain tissue of CPSP rats, ameliorating hyperalgesia symptoms in CPSP rats. The overexpression of <i>MEG3</i> weakened the inhibitory effect of EA on the Wnt/β-catenin pathway in the VPL region of the brain, exacerbating pain hypersensitivity and neuroinflammatory damage in the brain hemorrhage regions of CPSP rats. Suppressing the expression of <i>MEG3</i> in the VPL brain tissue of CPSP rats produced a therapeutic effect similar to that of EA intervention. EA could alleviate neuroinflammation and reduce pain in CPSP rats by suppressing the expression of <i>MEG3</i>. EA could regulate the Wnt/β-catenin signaling pathway via <i>MEG3</i>.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04547-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028413","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":"Salidroside Attenuates Cerebral Ischemia-Reperfusion Injury via ERβ/BNIP3-Mediated Mitochondrial Autophagy Activation in a Rat Model","authors":"Xing Rong,&nbsp;Peipei Lu,&nbsp;Yu Li,&nbsp;Hongxiang Wang,&nbsp;Yuanjia Yue,&nbsp;Huimin Wang,&nbsp;Zhao Ji,&nbsp;Lin Jiang","doi":"10.1007/s11064-025-04535-3","DOIUrl":"10.1007/s11064-025-04535-3","url":null,"abstract":"<div><p>This study aimed to assess the neuroprotective effects of salidroside (SAL) on cerebral ischemia-reperfusion injury (CIRI) in a rat model and to elucidate the underlying mechanisms, with a focus on the role of estrogen receptor beta (ERβ) and BCL2 interacting protein 3 (BNIP3)-mediated mitochondrial autophagy as potential therapeutic targets in ischemic stroke. A total of 165 female Sprague-Dawley rats were randomly assigned into 11 groups (<i>n</i> = 15 per group). One group served as the control. The remaining animals underwent bilateral ovariectomy and were subsequently allocated into the following groups: ovariectomy-only, middle cerebral artery occlusion/reperfusion (MCAO/R), estradiol control, ERβ inhibitor, two inhibitor arms (inhibitor-only and inhibitor-plus-SAL), three SAL treatment groups (low, mediummitochondrial division, high dose), and a positive control (edaravone). All groups, except the control and ovariectomy-only groups, were subjected to MCAO for one hour followed by 24 h of reperfusion. Neurological function, cerebral infarct volume, blood-brain barrier (BBB) permeability, and brain water content were evaluated. Histopathological alterations were assessed, and transmission electron microscopy was employed to detect autophagosomes. Western blot analysis was performed to quantify protein expression levels of ERβ, BNIP3, NIP3-like protein X, and microtubule-associated protein 1 A/1B-light chain 3. Administration of SAL and edaravone significantly reduced neurological impairment, infarct volume, BBB disruption, and cerebral edema in the MCAO/R model. SAL treatment upregulated ERβ and BNIP3 expression and enhanced mitochondrial autophagy-associated protein levels. These effects were attenuated by the use of ERβ and mitochondrial division inhibitors, indicating a mechanistic link between SAL-mediated neuroprotection and activation of the ERβ/BNIP3 signaling axis. SAL exerts a neuroprotective effect against CIRI in rats, primarily through activation of ERβ and enhancement of BNIP3-mediated mitochondrial autophagy. These findings suggest that modulation of the ERβ/BNIP3 pathway may represent a promising therapeutic approach for ischemic stroke.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028414","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":"Therapeutic Effect of Physical Activity in a Male Wistar Rat Model of Paraquat and Maneb-Induced Parkinson’s Disease","authors":"Youssef El Mekhlouf,&nbsp;Nezha Bouhaddou,&nbsp;Amal Dimaoui,&nbsp;Abdessamad Ittorahou,&nbsp;Ahmed Moussaif,&nbsp;Abdelghani Iddar,&nbsp;Mohammed El Mzibri,&nbsp;Abdellatif Bouayyadi,&nbsp;Abdelhalem Mesfioui","doi":"10.1007/s11064-025-04543-3","DOIUrl":"10.1007/s11064-025-04543-3","url":null,"abstract":"<div><p>Parkinson’s disease (PD) is characterized by impairments in motor control following the degeneration of dopamine-producing neurons located in the substantia nigra pars compacta. Environmental pesticides such as Paraquat (PQ) and Maneb (MB) contribute to the onset of PD by inducing oxidative stress (OS). This study evaluated the therapeutic efficacy of moderate physical activity (PA) on both motor and non-motor symptoms in a Wistar rat model of Paraquat and Maneb (PQ/MB) induced PD. Thirty male Wistar rats were randomly divided into six groups: control, exercise (EX), PQ/MB, PQ/MB + L-dopa, PQ/MB + EX, and PQ/MB + EX + L-dopa. PD was induced via intraperitoneal (IP) injections of PQ (5 mg/kg) and MB (0.05 mg/kg) administered twice weekly for six weeks, followed by four weeks of moderate exercise in the designated groups. Motor and non-motor behaviors were then assessed, and OS markers were analyzed in the prefrontal cortex (PFC), striatum (ST), and hippocampus (HP). In our model, PQ/MB exposure induced characteristic PD symptoms, including motor dysfunction, anxiety, depression, and memory deficits. These symptoms were accompanied by elevated malondialdehyde (MDA) levels and reduced activity of antioxidant enzymes. However, moderate PA significantly improved several parameters: it enhanced coordination and balance, reduced anxiety and depressive-like behaviors, improved memory performance, attenuated lipid peroxidation, and increased antioxidant defense mechanisms, particularly the activity of catalase (CAT) and superoxide dismutase (SOD). These findings suggest that PA is a promising non-pharmacological therapeutic approach for the management of both motor and non-motor symptoms of PD.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021772","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":"Astrocyte-Neuron Metabolic Synergies in Neurological Homeostasis and Disease","authors":"Jiahao Dong,&nbsp;Zihan Gao,&nbsp;Mingrui Liu,&nbsp;Binglu Qian,&nbsp;Cheng Yuan,&nbsp;Hui Liu,&nbsp;Ni Rao,&nbsp;Yingjiao Liu","doi":"10.1007/s11064-025-04548-y","DOIUrl":"10.1007/s11064-025-04548-y","url":null,"abstract":"<div><p>Metabolic synergy between astrocytes and neurons is key to maintaining normal brain function. As the main supporting cells in the brain, astrocytes work closely with neurons through intercellular metabolic synergy networks to jointly regulate energy metabolism, lipid metabolism, synaptic transmission, and cerebral blood flow. This important synergy is often disrupted in neurological diseases such as Alzheimer’s disease, Parkinson’s disease, and stroke. This study systematically explores the physiological basis of this intercellular collaboration and its dysfunctional manifestations in the aforementioned diseases, and provides detailed insights into how abnormalities in specific collaborative pathways (such as impaired lactate transport, disrupted glutamate cycling, or lipid processing defects) significantly contribute to disease progression. By elucidating the molecular mechanisms underlying these collaborative impairments, this study aims to identify potential therapeutic targets, with the core strategy being to restore these critical intercellular collaborative relationships to alleviate neurological diseases.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011796","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":"The Role of Neuroglia in Cognitive Longevity","authors":"Robert Zorec,&nbsp;Alexei Verkhratsky,&nbsp;Vladimir Parpura","doi":"10.1007/s11064-025-04545-1","DOIUrl":"10.1007/s11064-025-04545-1","url":null,"abstract":"<div><p>The concept of the central nervous system (CNS) reserve emerged from the mismatch often observed between the extent of brain pathology and its clinical manifestations. The cognitive reserve reflects an “active” capacity, driven by the plasticity of CNS cellular components and shaped by experience, learning, and memory processes that increase resilience. We propose that neuroglial cells are central to defining this resilience and cognitive reserve. These cells maintain CNS homeostasis through allostatic mechanisms and modulate responses to injury and/or disease. In this review, we first outline the concept of the CNS reserve and then explore the role of neuroglia in maintaining brain function throughout development and adulthood. We highlight astrocytes and oligodendrocytes in gray and white matter learning, respectively, and examine the function of microglia in immune surveillance. We conclude that neuroglia are key contributors to the cognitive reserve, with systems such as the noradrenergic pathway supporting tissue under stress and mitigating pathology through compensatory responses.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007825","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":"Correction to: Ameliorative Role of Phosphodiesterase-5 (PDE-5) Inhibitor “Avanafil” Via Modulating cAMP & cGMP Pathway Against Alzheimer’s Disease","authors":"Mohd Talib,&nbsp;Nazia Siddiqui,&nbsp;Prabhash Nath Tripathi,&nbsp;Ankit Chaudhary","doi":"10.1007/s11064-025-04546-0","DOIUrl":"10.1007/s11064-025-04546-0","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005562","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":"Probiotics Co-administered with LCM Enhance Antiepileptic Efficacy in the Experimental Post-traumatic Epilepsy Model","authors":"Ugur Aykin,&nbsp;Cumaali Demirtas,&nbsp;Sezin Kiroglu Uzun,&nbsp;Mehmet Yildirim","doi":"10.1007/s11064-025-04541-5","DOIUrl":"10.1007/s11064-025-04541-5","url":null,"abstract":"<div><p>The aim of the presented study was to investigate the effects of prebiotic inulin, probiotic VSL#3 (mixture of bacteria from 7 different species and 8 strains) and synbiotic (inulin + VSL#3) supplements applied together with lacosamide (LCM) on post-traumatic epilepsy (PTE). In addition, effectiveness of the relevant treatments on comorbid problems related to learning and memory, anxiety, motor performance and pain threshold that may develop together with seizures due to traumatic brain injury (TBI) and PTE was also examined using behavioral tests. In experiments, adult male Sprague-Dawley rats, divided into 6 groups, were given 30 mg/kg LCM or 1000 mg/kg inulin together with LCM as prebiotic, VSL#3 mixture containing 10 × 10⁹ CFU/kg bacterial colonies as probiotic and (inulin + VSL#3) as synbiotic for 28 days by oral gavage after mild-TBI was induced by weight-drop method and electroencephalogram electrodes were placed. In order to reveal the tendency to trauma-induced seizures, PTE was modeled by injection of 30 + 15 + 15 mg/kg pentylenetetrazole at subconvulsant doses at 30-min intervals on 7th, 14th, 21st and 28th days after TBI and seizures were scored according to Racine scale. Locomotor, cognitive and pain-related behaviors of animals other than seizures were also examined using open field, rotarod, elevated plus maze, radial arm maze, dynamic plantar and thermal plantar tests. It was determined that LCM applied alone was effective in seizure control related to PTE, but probiotic supplement in form of LCM + VSL#3 provided more effective seizure control. In addition, it was determined that probiotic VSL#3 applied together with LCM increased locomotor activity, both VSL#3 and inulin prevented the disorder in forced motor activity caused by LCM, and VSL#3 + inulin applied together with LCM increased mechanical pain threshold. It was concluded that probiotic VSL#3 combined with antiepileptic LCM provides more effective seizure control by strengthening the antiepileptic activity of LCM in management of PTE.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005561","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":"Kaempferol Plays a Neuroprotection Role by Alleviating Oxidative Stress via AKT/Nrf2/HO-1 Pathway and Inhibiting Apoptosis in Intracerebral Hemorrhage","authors":"Haoran Huo,&nbsp;Aobo Zhang,&nbsp;Yunpeng Shi,&nbsp;Yayu Zhuo,&nbsp;Chengrui Nan,&nbsp;Dongdong Yan,&nbsp;Liqiang Liu","doi":"10.1007/s11064-025-04544-2","DOIUrl":"10.1007/s11064-025-04544-2","url":null,"abstract":"<div><p>Intracerebral hemorrhage (ICH) is a common yet severe cerebrovascular disorder associated with high morbidity, disability, and mortality rates. Kaempferol (Kae), a natural flavonoid with potent antioxidant and anti-inflammatory properties, has shown promise in neuroprotection; however, its therapeutic potential in promoting neurological recovery after ICH remains unclear. In this study, we investigated the neuroprotective effects of Kae in ICH and explored its underlying mechanisms using in <i>vitro</i> and in <i>vivo</i> models. For in vitro experiments, primary hippocampal neurons were pretreated with Kae for 2 h before hemin exposure (24 h). In vivo, rats received intraperitoneal Kae injections for 5 days pre-operation and 3 days post-operation. Using a combination of techniques—including SOD (Superoxide dismutase), MDA (malondialdehyde), and GSH (glutathione) assays, mitochondrial membrane potential evaluation, flow cytometry, immunofluorescence, FJC staining, and TUNEL staining—we demonstrated that Kae exerts neuroprotective, antioxidant, and anti-apoptotic effects. Western blot analysis revealed that Kae mitigates oxidative stress (OS) by modulating the AKT/Nrf-2/HO-1 signaling pathway. Further mechanistic studies confirmed that Kae enhances this pathway, thereby reducing oxidative damage in both in vitro and in vivo settings. Additionally, Kae upregulated Bcl-2 expression while downregulating BAX and cleaved Caspase-3, highlighting its anti-apoptotic role. Our findings suggest that Kae protects against ICH-induced brain injury, potentially through the suppression of oxidative stress and apoptosis. This study provides novel insights into the therapeutic potential of Kae in ICH treatment.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005563","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":"Dapagliflozin Ameliorates Doxorubicin-Induced Chemobrain and Cognitive Abnormalities in Rats: Modulation of AKT/GSK-3β and Wnt/β-Catenin Pathways","authors":"Gehad Farouk Abdelhafez,&nbsp;Sylvia A. Boshra,&nbsp;Hagar B. Abo-Zalam,&nbsp;Sara M. Radwan","doi":"10.1007/s11064-025-04538-0","DOIUrl":"10.1007/s11064-025-04538-0","url":null,"abstract":"<div><p>Cognitive impairments are frequently observed in cancer survivors who received chemotherapy based on doxorubicin (DOX), attributable to oxidative stress, neuroinflammation, and the apoptotic effect of DOX. Dapagliflozin (DAPA) has gained significant attention attributable to its powerful anti-inflammatory, antioxidant, and anti-apoptotic characteristics. The present investigation seeks to assess the possible neuroprotective properties of DAPA in alleviating neurodegeneration and cognitive dysfunction caused by DOX. Chemobrain was induced by DOX (2 mg/kg, i.p.) once weekly for four weeks. Additionally, rats were treated with DAPA (2 mg/kg, p.o.) for 28 consecutive days. DAPA markedly mitigated behavioral deficits associated with cognitive impairment induced by DOX, as demonstrated by cognitive behavioral tests. Likewise, DAPA reversed histopathological abnormalities. Mechanistically, DAPA alleviated the oxidative stress induced by DOX by reducing tissue levels of NADPH oxidase 4 (NOX4) and malondialdehyde (MDA) while enhancing the activities of superoxide dismutase (SOD) and glutathione (GSH). Additionally, DAPA suppressed neuroinflammation by attenuating the production of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) in brain tissue, as well as the signaling pathways involved in apoptosis, including the Protein Kinase B (AKT)/Glycogen Synthase Kinase-3 beta (GSK-3β) pathway and the Wingless-related integration site (Wnt)/β-catenin pathway. Further evidence of DAPA’s anti-apoptotic effects was attributed to a decrease in the immunohistochemical expression of total caspase-3 and the p65 subunit of NF-κB (NF-κB-p65). DAPA induces neuroprotection against DOX-induced cognitive deterioration by providing antioxidant, anti-inflammatory, and anti-apoptotic effects.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04538-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990357","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}