Neurochemical Research最新文献

{"title":"Retraction Note: Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat","authors":"Jamshid Tabeshpour, Soghra Mehri, Khalil Abnous, Hossein Hosseinzadeh","doi":"10.1007/s11064-025-04493-w","DOIUrl":"10.1007/s11064-025-04493-w","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688560","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":"High-Intensity Interval Training Improves Memory Deficits in Obese Mice by Enhancing Osteocalcin-Driven Astrocytic BDNF Expression and Stimulating Hippocampal Neurogenesis","authors":"Hyukki Chang,&nbsp;Yea-Hyun Leem,&nbsp;Jonghoon Park,&nbsp;Jung-Eun Park,&nbsp;Soo Jin Yang,&nbsp;Hee-Sun Kim","doi":"10.1007/s11064-025-04504-w","DOIUrl":"10.1007/s11064-025-04504-w","url":null,"abstract":"<div><p>Obesity contributes to cognitive disorders, particularly memory impairment. Physical exercise is a non-pharmacological approach for enhancing weight management and promoting brain health. Especially, high-intensity interval training (HIIT) yields results comparable to or even exceeding those of traditional aerobic exercises. However, its nootropic effects and underlying mechanisms remain unclear. This study aims to investigate the cognitive-enhancing effects of high-intensity interval training (HIIT) in the context of neurotoxicity induced by a high-calorie diet, with particular emphasis on the role of osteocalcin (OCN)/GPR158 signaling in adult hippocampal neurogenesis. Mice were fed a high-fat, high-sucrose diet (HFHSD) for 12 weeks. They then participated in an 8-week HIIT program, with the training intensity determined based on their pre-assessed maximal running capacity (MRC). HIIT efficiently regulated body weight and feeding behavior while improving MRC. It also ameliorated HFHSD-induced memory deficits, as demonstrated by the modified Y-maze test, by promoting adult hippocampal neurogenesis, which was primarily localized to the dorsal hippocampus. Moreover, HIIT markedly increased astrocytic OCN/GPR158 signaling and significantly elevated BDNF expression in astrocytes within the dentate gyrus. Activation of the AKT/GSK3β pathway was also detected in OCN-positive astrocytes. This study collectively suggests a HIIT-specific mechanism, indicating that astrocytic OCN/GPR158 may contribute significantly to memory improvement in HFHSD-fed mice through its proneurogenic effects. Therefore, HIIT could serve as an effective strategy for combating the cognitive decline associated with metabolic disorders.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688557","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":"Nuclear Transport Receptor Importin-β Inhibition Enhances Cell Cycle Arrest Induced by CKS2 Knockdown to Suppress Neuroblastoma Progression","authors":"Shouhua Zhang,&nbsp;Xiaozhen Meng,&nbsp;Deng Xiang,&nbsp;Hui Huang,&nbsp;Yangfan Ge,&nbsp;Yishan Zhan,&nbsp;Kehao Li,&nbsp;Xiaoyun Tan","doi":"10.1007/s11064-025-04488-7","DOIUrl":"10.1007/s11064-025-04488-7","url":null,"abstract":"<div><p>Cyclin-dependent kinases regulatory subunit 2 (CKS2) is a key regulator of the cell cycle, but its role in neuroblastoma remains poorly understood. This study investigates the function and mechanisms of CKS2 in neuroblastoma through bioinformatics analyses, as well as in vitro and in vivo experiments. Data from the GEO and TCGA databases indicate that elevated <i>CKS2</i> expression is associated with poor prognosis in neuroblastoma. Analysis of clinical tumor samples and cell lines further confirmed that CKS2 was significantly overexpressed, particularly in high-risk neuroblastoma patient-derived tissues. Functional studies revealed that <i>CKS2</i> knockdown reduced cell proliferation and invasion, induced apoptosis, and caused cell cycle arrest in neuroblastoma cells. In vivo, tumors formed from <i>CKS2</i>-silenced cells showed markedly reduced growth. Mechanistically, <i>CKS2</i> knockdown decreased the phosphorylation of CDK1 (Thr161) and Cyclin B1 (Ser126), suggesting impaired cell division signaling. Treatment with importazole, an importin-β inhibitor, caused CKS2 to accumulate in the cytoplasm rather than in the nucleus, inhibiting proliferation and increasing apoptosis of neuroblastoma cells. Notably, the combination of <i>CKS2</i> knockdown and importazole treatment produced a stronger anti-tumor effect than either intervention alone. These findings demonstrate that CKS2 promotes neuroblastoma progression by facilitating cell division via the CDK1/Cyclin B1 complex. Targeting <i>CKS2</i>, especially in combination with nuclear import inhibition, offers a promising therapeutic strategy for neuroblastoma.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688559","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":"“Targeting Neuroimmune Pathways in Epilepsy: Advances in Mechanisms and Emerging Therapeutics”","authors":"Manish Ravikumar,&nbsp;Deenathayalan Uvarajan,&nbsp;Brindha Durairaj","doi":"10.1007/s11064-025-04489-6","DOIUrl":"10.1007/s11064-025-04489-6","url":null,"abstract":"<div><p>The interaction between immune system dysfunction and neuroinflammation is crucial for the development and progression of epilepsy. This study investigates the complex relationships between immune responses and the onset of epileptic seizures and highlights the influence of neuroinflammatory processes on neuronal integrity and seizure frequency. Key factors such as glial cell activation, release of pro-inflammatory cytokines, and disruption of the blood-brain barrier (BBB) are being investigated for their roles in immune-mediated neurological disorders. The review examines novel therapeutic approaches targeting neuroinflammatory pathways. It highlights their potential to reduce seizure onset and development while addressing challenges in translating research into clinical practice. This study aims to elucidate these pathways, address knowledge gaps and explore novel options for epilepsy treatment.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688555","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":"Melatonin Reduced Hyperexcitability and Enhanced Sleep Oscillations in the Hippocampus and Prefrontal Cortex of Aged Male Rats","authors":"Farnaz Karimani,&nbsp;Mehdi Eivani,&nbsp;Afsaneh Asgari Taei,&nbsp;Mohammad-Reza Abolghasemi Dehaqani,&nbsp;Leila Dargahi","doi":"10.1007/s11064-025-04497-6","DOIUrl":"10.1007/s11064-025-04497-6","url":null,"abstract":"<div><p>Aging is commonly associated with cognitive decline, particularly in memory, and is linked to neuronal hyperexcitability and disrupted sleep-related oscillations in key brain regions such as the hippocampus and prefrontal cortex. Melatonin has been proposed as a potential therapeutic agent to counteract age-related cognitive impairments. In this study, 24-month-old male Wistar rats were treated with melatonin (10 mg/kg, intraperitoneally) for 30 days. Local field potentials were recorded from the hippocampus and prefrontal cortex to assess neuronal activity. Memory performance was evaluated using the novel object recognition test, and qPCR measured expression levels of inflammatory and amyloidogenesis markers. Melatonin treatment significantly reduced neuronal hyperexcitability, enhanced delta and theta oscillations, and increased sleep spindle amplitude, which were associated with improved memory performance. Additionally, melatonin attenuated the expression of pro-inflammatory markers without affecting the expression of amyloidogenesis-related genes. These findings suggest that melatonin may enhance cognitive function in aging by modulating neuronal excitability, sleep oscillations, and neuroinflammatory processes.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688558","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":"Signaling Mechanisms Underlying the Glioprotective Effects of Guanosine Against Glucose Deprivation-Induced Glial Dysfunction","authors":"Larissa Daniele Bobermin,&nbsp;Caio César Ramalho Bezerra,&nbsp;Júlia Krebs-Rosa,&nbsp;Vanessa-Fernanda Da Silva,&nbsp;Izaviany Schmitz,&nbsp;Rômulo Rodrigo de Souza Almeida,&nbsp;Fernanda Becker Weber,&nbsp;Nikoli Zasso,&nbsp;Aline Longoni,&nbsp;Adriano Martimbianco de Assis,&nbsp;Carlos-Alberto Gonçalves,&nbsp;Diogo Onofre Souza,&nbsp;André Quincozes-Santos","doi":"10.1007/s11064-025-04498-5","DOIUrl":"10.1007/s11064-025-04498-5","url":null,"abstract":"<div><p>Glucose is a critical energy substrate for brain function; therefore, hypoglycemia or compromised glucose metabolism can lead to cognitive impairment and an increased risk for neurodegenerative and neuropsychiatric disorders. Astrocytes are glial cells that act as key regulators of brain glucose metabolism, thus representing important cellular targets for neuroprotection during glucose deprivation. Guanosine, a guanine-based purine, has shown neuroprotective properties in various central nervous system (CNS) disorders. As such, this study aimed to evaluate the potential glioprotective effects of guanosine in a glucose deprivation model, using C6 astroglial cells and focusing on redox imbalance, inflammatory and trophic responses, as well as putative signaling mechanisms associated with these effects. C6 astroglial cells were cultured under normal glucose conditions and subjected to glucose deprivation (culture medium without glucose), with or without guanosine (100 µM) for 12 h. Cytokine levels, oxidative stress markers, mitochondrial function, and NFκB, Nrf2/HO-1, and PI3K/Akt signaling were assessed via ELISA, RT-PCR, colorimetric and fluorescence assays. Glucose deprivation induced glial dysfunction, particularly changes in inflammatory response, redox homeostasis, and cytoprotective/survival signaling pathways. Guanosine prevented glucose deprivation-induced NFκB activation, reducing inflammatory markers (e.g., TNF-α, IL-1β) and restoring S100B secretion. Guanosine also upregulated Nrf2/HO-1 expression, improved antioxidant enzyme activities, mitigated oxidative stress, and preserved mitochondrial membrane potential. Additionally, guanosine restored PI3K/Akt expression and modulated glial-derived factors, including GDNF and TGF-β. By modulating the NFκB, Nrf2/HO-1, and PI3K/Akt pathways, guanosine offers a promising glioprotective strategy to mitigate astrocytic damage during hypoglycemia, potentially reducing CNS injury and associated neurodegeneration.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673684","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":"miRNA-105 Attenuates Hypoxic-Ischemic Brain Damage in Neonatal Rats by Inhibiting Apoptosis and Necroptosis","authors":"Junyan Liu,&nbsp;Hui Li,&nbsp;Yi Qu,&nbsp;Shiping Li,&nbsp;Fengyan Zhao","doi":"10.1007/s11064-025-04484-x","DOIUrl":"10.1007/s11064-025-04484-x","url":null,"abstract":"<div><p>Apoptosis and necroptosis contribute significantly to cell death in hypoxic-ischemic encephalopathy (HIE). While microRNA-105 (miR-105) is known to suppress both apoptosis and necroptosis in cardiac ischemia, its role in HIE remains unclear. This study investigated the effects of miR-105 on apoptosis and necroptosis in a neonatal rat model of HIE. MiR-105 agomir was administered intracerebroventricularly 6 h post-hypoxic-ischemia (HI). The characteristic apoptosis-related proteins (BNIP3, cleaved caspase 3), necroptosis mediators (RIP3, p-RIP3, p-RIP1, p-MLKL), cerebral infarction, and neurological deficits were analyzed. Results showed miR-105 was significantly downregulated in cerebral cortex from 6 to 48 h post-HI, concurrent with increased BNIP3 and RIP3 expression, and elevated apoptosis and necroptosis, at both 24 and 48 h. MiR-105 agomir treatment suppressed BNIP3 and RIP3 expression, reduced apoptosis and necroptosis, attenuated infarct volume, lowered neurological severity score, and improved spatial learning and memory abilities. In conclusion, miR-105 alleviates HI brain injury in neonatal rats by simultaneously inhibiting apoptosis and necroptosis, highlighting its potential as therapeutic agent for HIE.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673683","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":"Extracellular Matrix Proteins Differentiate Postnatal Mouse Retina Neurospheres into Neurons or Glia Profiles","authors":"Orquidia Guadalupe Méndez-Flores,&nbsp;Anna Carolina Rego Costa,&nbsp;Andrey Fabiano Lourenço de Aguiar,&nbsp;Yolanda Paes-Colli,&nbsp;Cláudia Maria Batista,&nbsp;Victor T. Ribeiro-Resende,&nbsp;Arturo Ortega,&nbsp;Ricardo A. de Melo Reis","doi":"10.1007/s11064-025-04500-0","DOIUrl":"10.1007/s11064-025-04500-0","url":null,"abstract":"<div><p>The mammalian retinal progenitor cells (RPC) exit the cell cycle through signaling of intrinsic and extrinsic factors and give rise to several types of neurons and Müller glia, following an organized spatial–temporal pattern. Extracellular matrix (ECM) plays an important role in retinal development, influencing RPC proliferation and differentiation into pro-gliogenic and/or neurogenic phenotypes. Here, we investigated how four different ECM constituents, fibronectin, vitronectin, collagen type IV and laminin-1 (α1β1γ1), added on coverslips previously treated with 10 µg/mL poly-L-lysine, could impact differentiation of retinal neurospheres generated with epidermal growth factor (EGF) 20 ng/mL and cultivated for four days. Progenitors (activated by muscimol, a GABA_A agonist), neurons (by KCl and/or AMPA, a glutamatergic agonist) and Müller glia (by ATP) show distinct functional responses in terms of calcium imaging due to the pattern of selective receptors and channels expressed during development. A highly heterogeneous cell population was generated when neurospheres were cultivated in different ECM molecules, suggesting the presence of high, medium, and low-responsive cells. As shown, collagen type IV or laminin-1 for 6 days in DMEM F12 had similar responses, revealing that nearly 55% of cells were responsive to KCl, 28–39% to AMPA, 18–28% to ATP and almost none to muscimol (less than 0.5%). On the other hand, in the presence of fibronectin, 56% of retinal neurospheres were induced to respond to KCl, 32% to AMPA, 33% to ATP and 2.8% to muscimol. Finally, neurospheres raised in vitronectin had around 67% of cells responsive to KCl, 41% to AMPA, less than 20% to ATP and 3% to muscimol. As expected, differentiated cells in the presence of fibronectin were immuno-labelled and expressed higher levels of glial fibrillary acidic protein (GFAP), compared to other substrates, while cultures prepared in the presence of vitronectin had increased expression of neuron-specific class III β-tubulin (TUJ-1), a neuronal marker. Altogether, our data suggest that, compared to laminin, a standard substrate, collagen and vitronectin increased the number of functional neurons, while fibronectin induced a two-fold increase in the number of glial cells in the developing cells of the mice retina.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681838","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 Multifaceted Role of P2X7R in Microglia and Astrocytes","authors":"Martina Bedetta,&nbsp;Paola Pizzo,&nbsp;Annamaria Lia","doi":"10.1007/s11064-025-04502-y","DOIUrl":"10.1007/s11064-025-04502-y","url":null,"abstract":"<div><p>The purinergic P2X7 receptor (P2X7R) is a unique ATP-gated ion channel that requires unusually high concentrations of extracellular ATP (eATP) for activation, making it a sensor of cellular stress and injury in the central nervous system. This review provides a comprehensive overview of P2X7R expression and function in glial cells, with a particular focus on microglia and astrocytes. We first outline the molecular characteristics of P2X7R and its distribution in brain cell types. In microglia, P2X7R regulates a broad spectrum of processes, including phagocytosis, autophagy, proliferation, and ultimately cell death, underscoring its dual role in neuroprotection and neurotoxicity. In astrocytes, P2X7R contributes to gliotransmission and inflammatory signaling, influencing neuronal excitability and synaptic function. We further explore the role of P2X7R in the context of both Alzheimer’s disease and epilepsy, where a dysregulated eATP-P2X7R signaling axis exacerbates neuroinflammation and glial dysfunction. Understanding the cell-specific roles of P2X7R in physiology and pathology provides new insights into glial biology and highlights its potential as a therapeutic target in brain diseases.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673685","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":"Research on the Correlation between BDNF Val76Met Polymorphism and Susceptibility to Changes of Cognitive Function in Rats Induced by Microwave Radiation","authors":"Mingzhao Zhang,&nbsp;Yang Wang,&nbsp;Yong Zou,&nbsp;Weijia Zhi,&nbsp;Xuelong Zhao,&nbsp;Jiajia Niu,&nbsp;Lina Du,&nbsp;Lizhen Ma,&nbsp;Lifeng Wang","doi":"10.1007/s11064-025-04480-1","DOIUrl":"10.1007/s11064-025-04480-1","url":null,"abstract":"<div><p>Microwave radiation is extremely sensitive to the brain and has been shown in animal models to affect memory and learning. Brain-derived neurotrophic factor (BDNF) is essential for neural function and brain development, with many single nucleotide polymorphisms (SNPs) in gene. Several neuropathological disorders have been linked to the BDNF Val66Met variation. Using CRISPR, we created BDNF Val76Met mutations in rats in this study. The rats were then subjected to X-band and S-band microwave radiation, respectively, at an average power density of 50 mW/cm² for 15 min every day for five days. We assessed cognitive capacity and investigated the neural structure and BDNF mRNA levels in the brain of rats. We discovered that BDNF Val76Met rats had impaired learning capacity and altered brain structure, with a decrease in BDNF mRNA. Meanwhile, we found that BDNF Val76Met rats exhibited aggravated structural and functional brain damage under 50mW/cm² microwave radiation, and showed higher sensitivity to S-band microwave due to the stronger penetration compared to X-band microwaves. Considering the genetic differences between animals and humans, more research is needed to determine the exact mechanism by which this SNP location affects cognitive changes caused by microwave radiation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666771","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}