Neurochemical Research最新文献

{"title":"Low-Dose Digoxin Ameliorates Age-Related Motor Learning Deficits in Mice","authors":"Junichi Hashimoto,&nbsp;Masatake Kai,&nbsp;Kazumasa Matsumoto-Miyai,&nbsp;Makoto Kondo","doi":"10.1007/s11064-026-04887-4","DOIUrl":"10.1007/s11064-026-04887-4","url":null,"abstract":"<div><p>Age-related decline in motor learning has been linked to impaired synaptic plasticity in the central nervous system; however, effective pharmacological strategies to restore these processes remain limited. Here, we investigated whether low-dose digoxin improves motor learning performance and dendritic spine structural plasticity in the middle-aged mice. Behavioral analyses revealed that low-dose digoxin (4 and 65 µg/kg) enhanced motor learning performance in the rotarod task, without affecting muscle strength or spontaneous locomotor activity. At the molecular level, digoxin increased sodium-potassium ATPase (Na/K ATPase) activity in the motor cortex. Morphological analyses using Golgi–Cox staining demonstrated a selective increase in filopodia and thin-type dendritic spines, which are associated with structural remodeling. Interestingly, these changes occurred without a detectable increase in the brain-derived neurotrophic factor (BDNF) protein level in the motor cortex as assessed by western blotting. Given the established role of BDNF in synaptic plasticity, these findings suggest that the observed structural changes are not primarily mediated by the BDNF upregulation. Instead, the data are consistent with engagement of activity-dependent structural remodeling pathways, including the neurotrypsin–agrin pathway, which links synaptic activity to dendritic filopodia formation. Furthermore, agrin-derived fragments have been reported to interact with Na/K ATPase, suggesting that this fragment may function as a molecular interface between extracellular signaling and synaptic structural remodeling. Together, these results indicate that modulation of Na/K ATPase activity enhances motor learning and dendritic spine remodeling in the aged motor cortex through mechanisms that do not require increased BDNF protein levels.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910585","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":"Strain-Specific Cognitive and Neurobiological Vulnerabilities to Social Isolation in Late Middle-Aged Wistar, Wistar-Kyoto, and Spontaneously Hypertensive Rats","authors":"Diana Mamedova,&nbsp;Olga Nedogreeva,&nbsp;Victor Aniol,&nbsp;Alexey Kvichansky,&nbsp;Liya Tretyakova,&nbsp;Vyacheslav Riga,&nbsp;Natalia Lazareva,&nbsp;Natalia Gulyaeva,&nbsp;Mikhail Stepanichev","doi":"10.1007/s11064-026-04889-2","DOIUrl":"10.1007/s11064-026-04889-2","url":null,"abstract":"<div><p>Social isolation and loneliness can lead to an increased risk of cardiovascular disease, cognitive decline, and psychiatric disorders. In this study, we investigated the impact of chronic social isolation on the cognitive functions and structural-functional state of the brain in middle-aged rats. Ten-month-old male spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats were housed individually for 15 weeks, while the control animals of respective strains were housed in groups. After 13 weeks, all the rats were trained to complete a spatial task in a Barnes maze. After the behavioral experiments, we analyzed the density of neurons, astrocytes, and microglia in the hippocampus. We also studied the expression of several genes in the hippocampus and frontal cortex, including <i>Aqp4</i>, <i>Cx3cr1</i>, <i>Tnfa</i>, <i>Il1b</i>, and <i>Il6</i>, using qPCR. We found that Wistar rats showed high resilience, maintaining stable physiological parameters and spatial learning abilities without significant neuroinflammatory or structural changes in the brain. In contrast, SHRs showed marked physiological vulnerability, characterized by a significant weight loss and severe memory impairments in the Barnes maze, accompanied by an elevated cytokine response in both brain regions studied. A different trajectory of neurobiological changes was observed in WKY rats. Although they had a high rate of hippocampal neurogenesis, which provided a compensatory effect on basic spatial learning and memory, they also showed decreased neuronal density and an elevated Il6 mRNA level, linked to impaired microglial Cx3cr1 mRNA expression. This study highlights the importance of genetic background in determining the outcome of brain aging in conditions of social isolation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896244","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":"Lactobacillus rhamnosus and Saccharomyces boulardii Attenuate LPS-Induced Cognitive and Affective Dysfunction Associated with Hippocampal Neuroinflammatory and Neurochemical Alterations","authors":"Durmuş Ali Aslanlar,&nbsp;K. Esra Nurullahoglu Atalık,&nbsp;Mehmet Öz,&nbsp;İbrahim Yıldız,&nbsp;Mehmet Tuğrul Yılmaz","doi":"10.1007/s11064-026-04883-8","DOIUrl":"10.1007/s11064-026-04883-8","url":null,"abstract":"<div><p>Lipopolysaccharide (LPS)-induced endotoxemia is widely used to model neuroinflammation-associated cognitive impairment, primarily involving activation of Toll-like receptor 4 (TLR4) and downstream NF-κB signaling. This study investigated whether probiotic interventions with <i>Saccharomyces boulardii</i> or <i>Lactobacillus rhamnosus</i> attenuate LPS-induced neurobehavioral and molecular alterations. Male Wistar rats were exposed to subchronic intraperitoneal LPS (0.25 mg/kg/day, 9 days) with or without concurrent probiotic administration. Behavioral assessments included the open field, elevated plus maze, forced swim, and novel object recognition tests. Hippocampal levels of inflammatory (TLR4, NF-κB, TNF-α, IL-6, GFAP), neurotrophic (BDNF, CREB), cholinergic (ACh, AChE), and apoptotic (p53, BAX, caspase-3) markers were quantified by ELISA. LPS exposure was associated with increased hippocampal TLR4 and NF-κB p65 levels, elevated TNF-α and IL-6 levels, and higher GFAP levels, alongside reduced BDNF and CREB levels, an altered ACh/AChE balance, and increased levels of apoptosis-related proteins. These molecular alterations coincided with deficits in recognition memory and increased anxiety- and depressive-like behaviors without affecting locomotor activity. Both <i>S. boulardii</i> and <i>L. rhamnosus</i> significantly attenuated these changes, reducing inflammatory markers, improving neurotrophic and cholinergic parameters, and partially attenuating apoptosis-related proteins. Behavioral impairments were concurrently ameliorated. Overall, these findings suggest that LPS-induced cognitive and behavioral alterations are closely associated with coordinated inflammatory, neurochemical, and apoptotic changes in the hippocampus. Because both probiotics were administered prophylactically, these findings indicate preventive rather than therapeutic efficacy. As all molecular outcomes were quantified by ELISA in whole-hippocampus homogenates, they should be interpreted as changes in protein levels rather than as demonstrated pathway activation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896295","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":"Mild Hypothermia Alleviates Ischemia and Reperfusion Injury by Activating PINK1/Parkin Mitophagy","authors":"Kailan Deng,&nbsp;Di Zhang,&nbsp;Yidan Chen,&nbsp;Qiumin Shao,&nbsp;Qian Zhang,&nbsp;Dan Wang,&nbsp;Fangyan Gong,&nbsp;Qin Li,&nbsp;Yue Wan,&nbsp;Mingmin Yan","doi":"10.1007/s11064-026-04878-5","DOIUrl":"10.1007/s11064-026-04878-5","url":null,"abstract":"<div><p>Ischemia-reperfusion (IR) injury is characterized by significant neuronal apoptosis and mitochondrial damage.Despite significant advancements in understanding the pathophysiological mechanisms of IR, effective therapeutic strategies remain limited. Previous studies have shown that mild hypothermia (MH) can significantly alleviate brain IR injury by reducing neuronal apoptosis and mitochondrial damage, while mitophagy plays a crucial role in maintaining cellular self-protection and mitochondrial homeostasis. However, the involvement of the PINK1/Parkin signaling pathway, a classical regulatory route for mitophagy, in the protective effects of MH against IR remains unclear. To investigate this phenomenon, we used neuron-like SH-SY5Y cells and employed an oxygen-glucose deprivation/reoxygenation (OGD/R) model to simulate the in vitro IR process, and conducted a series of cell experiments. Our results demonstrated that under MH conditions, the expression levels of PINK1 and Parkin were upregulated after 5 h of ischemia-hypoxia followed by 24 h of reoxygenation, and the protective effect on cells was also significant. Furthermore, the inhibition of the mitophagy pathway may partially eliminate the protective effect provided by MH against OGD/R-induced damage.These findings indicate that the protective effects of MH against IR is mediated, at least in part, through the PINK1/Parkin-dependent mitophagy pathway.This study provides new insights into the mechanisms by which MH mitigates IR injury and may offer potential therapeutic targets for treating IR-related diseases.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885879","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":"SIRT1 Activation Ameliorates Neuroinflammation and Cognitive Impairment in a Murine SAE Model and is Associated with the Nrf2/GPX4 Pathway","authors":"Yue Zhang,&nbsp;Qingzhen Liu,&nbsp;Haishu Zhao,&nbsp;Zhi Liu,&nbsp;Mengna Liu,&nbsp;Yao Ning,&nbsp;Qing Ji,&nbsp;Lidong Zhang","doi":"10.1007/s11064-026-04876-7","DOIUrl":"10.1007/s11064-026-04876-7","url":null,"abstract":"<div><p>Sepsis-associated encephalopathy (SAE) is a devastating condition with high mortality and cognitive sequelae, yet no effective treatments. This study investigates the neuroprotective potential of selective Sirtuin 1 (SIRT1) activation using the synthetic agonist SRT1720 in a male C57BL/6 J murine model of SAE. Transcriptomic profiling of the hippocampus revealed a specific disruption in glutathione and arachidonic acid metabolism pathways, indicating a metabolic priming for ferroptosis. We demonstrate that SIRT1 activation improves survival and ameliorates cognitive deficits by concurrently attenuating hippocampal ferroptosis and neuroinflammation. We observed that this protection was associated with the upregulated protein expression of Nrf2 and GPX4, key regulators of ferroptosis. Mechanistically, SIRT1 activation suppressed hippocampal ferroptosis, marked by reduced lipid peroxidation (ROS and MDA). Concurrently, it attenuated neuroinflammation by suppressing microglial activation and NLRP3 inflammasome activity, thereby decreasing the maturation of proinflammatory cytokines. These findings suggest SIRT1 activation coordinately counteracts both ferroptotic and inflammatory damage in SAE, presenting a compelling therapeutic strategy.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879069","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":"Comparative Effects of Quercetin and its α- and β-D-glucoside Derivatives in LPS-Stimulated C6 Astroglial Cells","authors":"Michele Goulart dos Santos,&nbsp;Tainá Guillante,&nbsp;Rafael Felipe de Aguiar,&nbsp;Marcelo Augusto Germani Marinho,&nbsp;Diele Bopsin da Luz,&nbsp;Marie Demonceaux,&nbsp;Claude Solleux,&nbsp;Lucia Emanueli Schimith,&nbsp;Carlos Eduardo da Rosa,&nbsp;Corinne André-Miral,&nbsp;Bruno Dutra Arbo,&nbsp;Mariana Appel Hort","doi":"10.1007/s11064-026-04875-8","DOIUrl":"10.1007/s11064-026-04875-8","url":null,"abstract":"<div><p>Neuroinflammation is a response of the central nervous system to injury, infection, or disease, involving the activation of glial cells and the release of cytokines and reactive species. When sustained or dysregulated, it contributes to the progression of neurological disorders. Quercetin (Que) is one of the most extensively studied flavonoids; however, its therapeutic application is limited by low bioavailability. Glucosylation has therefore emerged as a strategy to improve the physicochemical and biological properties of flavonoids. Previously, we synthesized the derivative quercetin-3’-α-D-glucoside (Que-3α) and characterized its pharmacokinetic profile and in vitro cytotoxicity. Here, we investigated the anti-inflammatory and antioxidant effects of Que and its derivatives, including the recently synthesized Que-3α and the naturally occurring β-glucoside, quercetin-3-β-D-glucoside (Que-3β), in a lipopolysaccharide (LPS)-induced inflammation model using C6 astroglial cells. Cells were pretreated for 2 h with the compounds (15 and 30 µM) and then stimulated with LPS (10 µg/mL) for 24 h. The compounds preserved mitochondrial activity, while Que and Que-3α reduced LPS-induced reactive oxygen species production, increased cell viability, and decreased apoptosis and necrosis. Notably, the Que-3α reduced iNOS expression, indicating more effective modulation of inflammatory mediators compared with the aglycone. These findings reinforce the biological properties of Que and suggest that α-glucosylation preserves the beneficial actions of Que while enhancing pharmacodynamic features relevant to neuroinflammation.</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":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863312","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":"Study on the Expression of MiR-642b-3p in Spontaneous Intracerebral Hemorrhage and Its Regulatory Mechanism on Endothelial Cell Injury","authors":"Zhi Cao,&nbsp;Linting Yin,&nbsp;Xinyong Zhang,&nbsp;Enhui Hong,&nbsp;Jiansheng Du,&nbsp;Rui Liang,&nbsp;Youjia Tang,&nbsp;Guofeng Zhang","doi":"10.1007/s11064-026-04863-y","DOIUrl":"10.1007/s11064-026-04863-y","url":null,"abstract":"<div><p>Spontaneous cerebral hemorrhage (sICH) is one of the cerebrovascular diseases with the highest mortality rate. MicroRNAs (miRNAs) are implicated in the regulation of various pathological processes, however, the specific function of miR-642b-3p in sICH remains unclear. Serum miR-642b-3p levels of sICH patients was determined. A thrombin-induced human brain microvascular endothelial cell (hBMECs) injury model was established. Cell viability, apoptosis, inflammatory factors, and related protein expression were assessed using CCK-8 assay, flow cytometry, ELISA, and Western blot. The targeting relationship between miR-642b-3p and CCNA2 was validated via a dual-luciferase reporter assay. MiR-642b-3p in the serum of ICH patients was significantly increased. Following thrombin induction, miR-642b-3p was upregulated in hBMECs, accompanied by decreased cell viability, increased apoptosis, elevated production of inflammatory factors, upregulated expression of pro-apoptotic proteins (Bax and cleaved caspase-3), and downregulated expression of anti-apoptotic protein (Bcl-2). Additionally, the protein levels of tight junction markers ZO-1 and occludin were markedly decreased. Notably, inhibition of miR-642b-3p significantly reversed these thrombin-induced changes and alleviated cell damage. Mechanistically, CCNA2was confirmed as a direct downstream target gene of miR-642b-3p. MiR-642b-3p is upregulated in sICH and mediates thrombin-induced endothelial cell injury, at least in part, by targeting CCNA2. These findings suggest that the miR-642b-3p/CCNA2 axis may represent a potential mechanistic pathway involved in ICH-induced blood-brain barrier disruption.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838074","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 Mechanism of Long Non-coding RNA GABPB1-AS1/SLC12A5 Regulating Neuronal Ferroptosis in Epileptic Seizures","authors":"Qian Jiang,&nbsp;Guo Tang,&nbsp;Tao Xu,&nbsp;Jiao Liu,&nbsp;Xue-Ming Zhong,&nbsp;Rui Song,&nbsp;Yang-Mei Chen","doi":"10.1007/s11064-026-04862-z","DOIUrl":"10.1007/s11064-026-04862-z","url":null,"abstract":"<div><p>Epilepsy, a common neurological disorder, is distinguished by abnormal neuronal activity. This study explored the mechanism of the long non-coding RNA (lncRNA) GABPB1-AS1/<i>SLC12A5</i> pathway modulating neuronal ferroptosis during epileptic seizures. Loss- and gain-of-function approaches were conducted in a mouse model of kainic acid-induced seizures and glutamic acid (Glu)-treated HT22 neurons to explore the regulatory effect of lncRNA GABPB1-AS1/<i>SLC12A5</i> on neuronal ferroptosis. Mouse seizures were assessed using the Racine scale. LncRNA GABPB1-AS1, SLC12A5, and ferroptosis-related markers were measured <i>via</i> RNA quantification, Western blot, and immunofluorescence. The direct or indirect interaction between lncRNA GABPB1-AS1 and SLC12A5 was validated using RIP, RNA pull-down, and Co-IP assays. CHX chase and ubiquitination assays assessed SLC12A5 stability and ubiquitination levels regulated by lncRNA GABPB1-AS1. LncRNA GABPB1-AS1 was upregulated in the hippocampal CA1 region of KA-induced mice. LncRNA GABPB1-AS1 knockdown suppressed neuronal ferroptosis—lowering Fe²⁺, MDA, and lipid peroxidation, while raising GSH, SLC7A11, and GPX4. Its knockdown also reduced seizure scores and frequency, prolonged seizure latency, and shortened seizure duration. An in vitro experiment verified the suppressive effect of lncRNA GABPB1-AS1 knockdown on neuronal ferroptosis. In addition to a direct binding relationship, this lncRNA further recruited the E3 ligase PRKN to enhance SLC12A5 ubiquitination and proteasomal degradation. <i>SLC12A5</i> overexpression inhibited Glu-induced ferroptosis, and <i>SLC12A5</i> knockdown partially reversed the effects exerted by lncRNA GABPB1-AS1. LncRNA GABPB1-AS1 recruits the E3 ligase PRKN to promote ubiquitination and proteasomal degradation of SLC12A5, thereby downregulating SLC12A5 expression and facilitating hippocampal neuronal ferroptosis that mediates epileptic seizures.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838077","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":"Atorvastatin Exerts Context-Dependent Metabolic and Beneficial Effects on Behavior and Apoptotic Signaling in a Cafeteria Diet–Induced Metabolic Dysfunction Model","authors":"Ítalo Leonardo Diogo,&nbsp;Grazielle Aparecida Silva Maia,&nbsp;Israel José Pereira Garcia,&nbsp;Herica de Lima Santos,&nbsp;Vanessa Faria Cortes,&nbsp;Leandro Augusto Barbosa,&nbsp;Valéria Ernestânia Chaves,&nbsp;Luciana Estefani Drumond Carvalho","doi":"10.1007/s11064-026-04874-9","DOIUrl":"10.1007/s11064-026-04874-9","url":null,"abstract":"<div><p>The growing prevalence of obesity has been associated with metabolic and neurobiological alterations that compromise brain integrity and behavior. Diet-induced obesity, often accompanied by hypercholesterolemia, activates apoptotic signaling pathways in the central nervous system, contributing to cognitive and behavioral impairments. This study evaluated the effects of atorvastatin on behavioral performance and apoptotic signaling pathways in the hippocampus and cerebral cortex of rats subjected to a hypercaloric cafeteria diet. Male Wistar rats were assigned to four groups: control diet (CTR), control diet plus atorvastatin (ATOR), cafeteria diet (CAF), and cafeteria diet plus atorvastatin (CAF+ATOR), and exposed to the diets for 24 days. Body weight, adiposity, and circulating cholesterol levels were measured to validate the metabolic model. Behavioral assessments included locomotor activity, immobility time, and recognition memory. The expression of pro-caspase−8, pro-caspase−9, and apoptosis-inducing factor (AIF) was quantified in frontal cortex and hippocampus. The cafeteria diet increased adiposity and circulating cholesterol levels, confirming metabolic dysfunction, whereas atorvastatin reduced cholesterol levels and prevented retroperitoneal fat accumulation. In addition, the cafeteria diet altered the expression of apoptosis-related proteins in the hippocampus and cortex, whereas atorvastatin attenuated these changes. Cafeteria-fed rats showed reduced exploratory activity and increased immobility. Spatial memory was impaired by both atorvastatin and the cafeteria diet but preserved in the CAF+ATOR group. Novel object recognition was impaired only in the ATOR group. These findings indicate that atorvastatin exerts context-dependent effects under conditions of diet-induced metabolic dysfunction.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Experimental timeline and proposed mechanisms underlying the effects of atorvastatin treatment in cafeteria diet-induced obesity. Cafeteria diet-induced obesity promoted hypercholesterolemia, increased adiposity, behavioral impairments, and alterations of intrinsic and extrinsic apoptotic pathways in the hippocampus and cerebral cortex of rats. Atorvastatin treatment attenuated apoptotic signaling, reduced metabolic dysfunction, and improved exploratory and memory-related behavioral alterations, indicating neuroprotective effects under diet-induced metabolic stress. The figure was created using Canva (Canva Pty Ltd., Sydney, Australia).</p></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-026-04874-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838319","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":"Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Alleviate Age-Related Insomnia in Rats by Suppressing Neuronal Ferroptosis in the Hippocampal Dentate Gyrus","authors":"Haiming Li,&nbsp;Ruining Liang,&nbsp;Zhenhui Li,&nbsp;Miao Wang,&nbsp;Xiaojuan Tang,&nbsp;Guangke Zuo,&nbsp;Hailong Zhu,&nbsp;Wenjun Cui,&nbsp;Yanling Hu,&nbsp;Xingping Zhang","doi":"10.1007/s11064-026-04872-x","DOIUrl":"10.1007/s11064-026-04872-x","url":null,"abstract":"<div><p>Age-related insomnia (ARI) is becoming increasingly prevalent among the elderly and remains inadequately addressed by conventional pharmacotherapy, prompting growing interest in stem cell–based alternatives. The present study investigated whether exosomes derived from umbilical cord mesenchymal stem cells (UCMSC-Exos) ameliorate ARI by suppressing hippocampal neuronal ferroptosis. UCMSCs were isolated from Sprague–Dawley rats on gestational day 21, and UCMSC-Exos were purified from passage 3 supernatants by ultracentrifugation. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting confirmed characteristic exosomal morphology with a mean diameter of 118.4 nm, positive expression of TSG101, CD9, and CD81, and absence of Calnexin. Following tail vein injection of DiD-labeled UCMSC-Exos in rats, DiD signals were traceable for 21 days. An ARI model was established in adult male rats using D-galactose combined with para-chlorophenylalanine, and animals were randomized into Sham, ARI, ARI-UCMSC-Exos, and ARI-Fer-1 groups. Morris water maze, elevated plus maze, open field tests, and electroencephalography demonstrated that UCMSC-Exos reversed behavioral deficits and prolonged total and slow-wave sleep. Hematoxylin-eosin, Nissl, and Golgi staining revealed restored dentate gyrus neurons with increased dendritic number and length, while transmission electron microscopy showed improved synaptic and mitochondrial ultrastructure. Prussian blue staining, ELISA, and western blotting further indicated that UCMSC-Exos reduced Fe³⁺, glutamate, and reactive oxygen species while elevating cysteine, glutathione, GPX4, 5-HT, and BDNF. Collectively, UCMSC-Exos alleviate sleep disturbance in ARI rats by inhibiting hippocampal neuronal ferroptosis, highlighting their therapeutic potential for ARI.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838395","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}