Neurochemistry international最新文献

{"title":"Clinically relevant infraorbital nerve deflation and chronic constriction injury models of trigeminal neuralgia display unifying mechanisms","authors":"Srilakshmi Satti ,&nbsp;Shwetali Ramteke ,&nbsp;Sowmya Chaganti ,&nbsp;Hara Prasad Padhy ,&nbsp;Gananadhamu Samanthula ,&nbsp;Manoj P. Dandekar","doi":"10.1016/j.neuint.2025.106052","DOIUrl":"10.1016/j.neuint.2025.106052","url":null,"abstract":"<div><h3>Background</h3><div>Trigeminal neuralgia is a debilitating pain condition that occurs due to the deflation of trigeminal nerve. Herein, we developed clinically relevant trigeminal neuralgia model using a distal infraorbital trigeminal nerve chronic deflation injury (dIoN CDI) in male and female rats. The results were compared with an existing distal infraorbital nerve chronic constriction injury (dIoN CCI) model.</div></div><div><h3>Methods</h3><div>Pain-related assessments were conducted by von-Frey filaments, orofacial-pain assessment device (OPAD), grooming time and rat-grimace scale (RGS). Anxiodepressive-phenotypes were assessed by elevated-plus maze test (EPM), sucrose-preference test (SPT), forced-swim test (FST), splash test. Brain, trigeminal nerve, faeces and blood samples were collected for molecular analysis.</div></div><div><h3>Results</h3><div>Rats subjected to dIoN CCI and dIoN CDI surgery displayed a decrease in von-Frey threshold and lick number in OPAD. The grooming time and RGS also indicated development of pain. A significant decrease in sucrose consumption in male rats and less exploration of open arms in EPM test by female rats, indicated the development of chronic pain-generated anxiodepressive behaviors. In biomarkers analysis, dIoN CCI and dIoN CDI groups showed elevated expression of calcitonin gene-related peptide and substance P in spinal trigeminal nucleus and/or ganglia. These groups also showed enhanced levels of dopamine, acetylcholine, 5-HT, and corticosterone and decreased concentration of GABA and noradrenaline in frontal and somatosensory cortices, brainstem and plasma. We also noted altered levels of sex hormones, fecal short-chain fatty acids, and occludin expression in the colon.</div></div><div><h3>Conclusion</h3><div>These results indicate that both trigeminal neuralgia models display unifying principles in male and female rats.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106052"},"PeriodicalIF":4.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051527","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":"Developmental neuroplasticity enables recovery from anesthetic-induced synaptic perturbations in the immature brain","authors":"Lixi Chen ,&nbsp;Zhiduo Zhang ,&nbsp;Shana Yang ,&nbsp;Yun Tang ,&nbsp;Xuanhe Wang ,&nbsp;Wenfu Li ,&nbsp;Lin Yang ,&nbsp;Chenyi Guo ,&nbsp;Shunchang Fang ,&nbsp;Wenhui Xiao ,&nbsp;Minbiao Yan ,&nbsp;Yonglin Li ,&nbsp;Taixuan Peng ,&nbsp;Boxing Li ,&nbsp;Xiao Min Zhang ,&nbsp;Lianyan Huang","doi":"10.1016/j.neuint.2025.106051","DOIUrl":"10.1016/j.neuint.2025.106051","url":null,"abstract":"<div><div>General anesthetics are essential in pediatric medicine, yet concerns persist regarding their potential neurotoxic effects on the developing brain. Whether transient synaptic disruptions caused by anesthesia lead to long-term deficits or are mitigated by endogenous plasticity remains unresolved. Here, we use longitudinal <em>in vivo</em> two-photon imaging in awake mice to investigate the structural and functional consequences of a single, clinically relevant exposure to sevoflurane at postnatal day 20. We find that sevoflurane induces transient behavioral hyperactivity and suppresses filopodia elimination. Remarkably, these effects are fully reversed within 24 h. Across a 10 days follow-up, we observe no persistent alterations in synaptogenesis, neuronal activity, motor learning, or anxiety-like behavior. Electrophysiological recording and calcium imaging further confirm the restoration of normal firing and synaptic transmission in layer 5 pyramidal neurons. These findings reveal a dual-phase recovery mechanism—acute plasticity followed by chronic convergence, highlighting the developing brain's intrinsic resilience to transient anesthetic insults. Our study redefines sevoflurane not as a source of irreversible neurotoxicity but as a temporary challenge that can be effectively buffered by developmental neuroplasticity, offering important reassurance for its continued use in pediatric anesthesia.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106051"},"PeriodicalIF":4.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032545","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":"Dynamic interaction of oligodendrocyte precursor cells with other cell types in the central nervous system","authors":"Jiali Li ,&nbsp;Shangyao Qin ,&nbsp;Hong Liu ,&nbsp;Ziwei Dai ,&nbsp;Zhida Lan ,&nbsp;Yimin Yuan ,&nbsp;Zhida Su","doi":"10.1016/j.neuint.2025.106050","DOIUrl":"10.1016/j.neuint.2025.106050","url":null,"abstract":"<div><div>Traditionally, oligodendrocyte precursor cells (OPCs) were primarily regarded for their differentiation potential to mature oligodendrocytes that ensheath central nervous system (CNS) axons through myelin formation. Recent breakthroughs in single-cell sequencing and <em>in vivo</em> imaging technologies have revolutionized our understanding, revealing that OPCs engage in extensive dynamic interactions with diverse CNS cell populations during neurodevelopment, tissue homeostasis maintenance, and pathological microenvironment remodeling. Notably, while OPCs exhibit relatively conserved phenotypic signatures, their functional plasticity within heterogeneous microenvironments demonstrates significant spatial specificity and disease-context dependence. In this review, we will systematically sort out the molecular interaction mechanism between OPCs and neurons, astrocytes, microglia, and vascular endothelial cells, deeply analyze their dynamic functional profiles, and focus on discussing: (1) the fine-tuning regulatory model of neuronal circuits mediated by OPCs at the developmental stage (2) the bidirectional regulatory mechanism of OPCs involved in maintaining the metabolic-immune balance under homeostasis; (3) OPC functional reprogramming in the pathological process of multiple sclerosis, cerebral ischemia, etc. This review aims to consolidate current evidence into a cohesive perspective on OPC multimodal functions, evaluate non-myelinating contributions, and discuss promising therapeutic targets for neural regenerative medicine.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106050"},"PeriodicalIF":4.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026557","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":"Multi-omics reveals changes in astrocyte fatty acid metabolism during early stages of Alzheimer's disease","authors":"Jie Zhong ,&nbsp;Manhui Li ,&nbsp;Ziwei Dai ,&nbsp;Jun Wan","doi":"10.1016/j.neuint.2025.106049","DOIUrl":"10.1016/j.neuint.2025.106049","url":null,"abstract":"<div><h3>Background</h3><div>Although astrocytes are known to contribute to Alzheimer's disease (AD) progression, their dynamic molecular alterations remain poorly characterized, particularly in early stages of the disease.</div></div><div><h3>Methods</h3><div>We performed multi-omics profiling (transcriptomics, proteomics, spatial metabolomics) of astrocytes from APP/PS1 and WT mice to characterize dynamic changes during AD progression. To assess similar changes in early human AD, we analyzed single-nucleus RNA sequencing data from human samples.</div></div><div><h3>Results</h3><div>Transcriptomic analysis of astrocytes from APP/PS1 and WT mice at five time points (2, 4, 6, 9, and 12 months of age) showed notable gene expression differences at 6 months, with reduced activity in fatty acid metabolism pathways (e.g., PPAR signaling, biosynthesis of unsaturated fatty acids). An astrocyte-specific metabolic model confirmed these disruptions. Proteomic analysis corroborated this by showing decreased activity in pathways like butanoate metabolism and PPAR signaling. Spatial metabolomics of brain slices from APP/PS1 and WT mice highlighted fatty acid enrichment in the hippocampus and cortex, alongside differential metabolites specific to the AD mouse model. Single-cell RNA sequencing analysis of human brain samples further showed fatty acid metabolism abnormalities in astrocytes from early AD cases versus controls, emphasizing its role in AD progression.</div></div><div><h3>Conclusion</h3><div>Our study identified abnormal fatty acid metabolism as an early feature of astrocytes in AD, suggesting an association between dysregulated fatty acid metabolism and disease progression.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106049"},"PeriodicalIF":4.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937974","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":"Impaired lysosomal proteolysis in developing neurons induces protein aggregation and disrupts morphogenesis and neuromaturation","authors":"Yinping Zhou ,&nbsp;Yuuki Fujiwara ,&nbsp;Mai Shirazaki ,&nbsp;Xiaoye Tian ,&nbsp;Gen Igarashi ,&nbsp;Hiroto Yamauchi ,&nbsp;Kazunori Imaizumi ,&nbsp;Hideki Hayakawa ,&nbsp;Ko Miyoshi ,&nbsp;Taiichi Katayama","doi":"10.1016/j.neuint.2025.106048","DOIUrl":"10.1016/j.neuint.2025.106048","url":null,"abstract":"<div><div>Lysosomes play a central role in the degradation of intracellular substances. Through this degradative capacity, lysosomes contribute to biological homeostasis and are particularly critical for the maintenance and function of neurons. Deficiencies in various lysosomal proteins cause a group of conditions known as lysosomal storage disorders, which often present with developmental delay and other neurological symptoms. In addition, defects in lysosomal function and the autophagic pathways that deliver intracellular substrates to lysosomes have been linked to neurodevelopmental disorders. However, the contribution of lysosomal degradative capacity to neurodevelopment has not been well appreciated. In this study, we aimed to examine the relationship between overall lysosomal proteolytic capacity and neuronal development using primary cultured neurons at early developmental stages. We found that lysosomal protein expression and proteolytic activity increased with neuronal maturation, suggesting that lysosomal proteolysis may play an important role in neuronal development. Treatment of cultured neurons with specific inhibitors of lysosomal proteases during development impaired morphogenesis, as indicated by a significant decrease in neurite length and complexity, along with decreased expression of neuronal lineage marker proteins. Furthermore, we observed that neurons with development impaired by lysosomal protease inhibition accumulated aggregated proteins—some of which were ubiquitinated—in the cytoplasm. These aggregates were enriched with various proteins related to neurodevelopment. These findings provide new insights into the previously underappreciated role of lysosomes in neuronal development.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106048"},"PeriodicalIF":4.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937915","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":"Imbalance of NKCC1/KCC2 contributes to the pathogenesis of primary focal hyperhidrosis","authors":"Ru-Jie Zheng ,&nbsp;Nan-Long Lin ,&nbsp;Meng-Long Zhang ,&nbsp;Rui-Qin Qiu ,&nbsp;Feng-Qiang Yu ,&nbsp;Xu Li ,&nbsp;Jian-Bo Lin","doi":"10.1016/j.neuint.2025.106043","DOIUrl":"10.1016/j.neuint.2025.106043","url":null,"abstract":"<div><h3>Background</h3><div>Primary focal hyperhidrosis (PFH) is characterized by excessive sweating in localized regions, significantly impacting patients' quality of life. The imbalance between sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) disrupts chloride ion homeostasis, potentially contributing to the pathogenesis of PFH.</div></div><div><h3>Methods</h3><div>Sweat gland tissues from 76 healthy controls and 76 PFH patients were collected. Expression levels of NKCC1 and KCC2 were assessed using quantitative real-time PCR and Western blotting. Primary sweat gland cells isolated from PFH patients (PFH-SG) and controls (NPFH-SG) were subjected to NKCC1 knockdown via lentiviral shRNA transfection. A hyperhidrosis mouse model was induced by intraperitoneal injection of pilocarpine hydrochloride, and mice were pretreated with the NKCC1 inhibitor bumetanide for one week. Sweat secretion, serum acetylcholine, and chloride ion concentrations were measured. Expression levels of aquaporin 5 (AQP5), brain-derived neurotrophic factor (BDNF), and neuregulin-1 (NRG-1) proteins were analyzed.</div></div><div><h3>Results</h3><div>PFH tissues showed significantly elevated NKCC1 and decreased KCC2 expression compared to controls, correlating with lower sweat chloride levels. NKCC1 knockdown in PFH-SG cells reduced elevated AQP5 expression. In vivo, bumetanide treatment markedly reduced sweat secretion, lowered serum acetylcholine, and restored chloride ion concentrations in hyperhidrosis mice. Furthermore, bumetanide treatment significantly decreased expressions of BDNF and NRG-1 in sympathetic ganglia axons, indicating attenuation of sympathetic hyperactivity associated with hyperhidrosis. NKCC1/KCC2 imbalance contributes significantly to PFH pathology.</div></div><div><h3>Conclusions</h3><div>Bumetanide effectively improves this imbalance, reducing excessive sweating and modulating related neurotransmitter signaling, offering potential therapeutic avenues for PFH.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106043"},"PeriodicalIF":4.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937899","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":"Decoding the role of m6A RNA methylation regulators in psychiatric and substance use disorders","authors":"Ji Sun Koo ,&nbsp;Huiping Zhang","doi":"10.1016/j.neuint.2025.106035","DOIUrl":"10.1016/j.neuint.2025.106035","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) is the most prevalent internal modification of eukaryotic mRNA and plays a crucial role in regulating gene expression. This dynamic and reversible epitranscriptomic mark responses to both environmental and internal cues and influences RNA stability, splicing, translation, and localization. In the central nervous system, m⁶A modifications are tightly regulated and critically involved in neural development, synaptic plasticity, learning, memory, and stress responses. These modifications are governed by a complex and responsive network of regulatory proteins, including writers (methyltransferases), erasers (demethylases), and readers (RNA-binding proteins). Emerging evidence indicates that dysregulation of m⁶A regulators contributes to the pathophysiology of various psychiatric disorders. Altered expression or function of m⁶A-related genes has been associated with neuroadaptive changes underlying conditions such as schizophrenia, depression, bipolar disorder, and substance use disorder. This review provides an overview of the molecular mechanisms of m⁶A modification, highlights the roles of m⁶A regulators in psychiatric disorders, summarizes recent findings, and discusses potential therapeutic strategies targeting m6A pathways. A better understanding of m⁶A-mediated mechanisms may advance the diagnosis and treatment of neuropsychiatric conditions.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106035"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924972","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":"Transcranial direct current stimulation attenuates cerebral ischemia-reperfusion injury by inhibiting neuronal pyroptosis via Netrin-1","authors":"Ying Wang ,&nbsp;Hao Liu ,&nbsp;Ping Li ,&nbsp;Zhuohang Zhang ,&nbsp;Yingxi He ,&nbsp;Yu Chen ,&nbsp;Yan Peng ,&nbsp;Bo Wang ,&nbsp;Linlin Jiang ,&nbsp;Changhong Li ,&nbsp;Qiyan Zhu ,&nbsp;Lingchuan Niu","doi":"10.1016/j.neuint.2025.106041","DOIUrl":"10.1016/j.neuint.2025.106041","url":null,"abstract":"<div><div>The significant role of pyroptosis in the early pathogenesis of ischemic stroke underscores the urgent need for effective management strategies. Transcranial direct current stimulation (tDCS), a noninvasive modality for modulating brain activity, has been shown to confer neuroprotection by inhibiting neuroinflammation during the acute phase of stroke. However, the specific mechanisms underlying the effect of tDCS on neuronal pyroptosis remain largely unexplored. We established brain I/R injury in adult male Sprague Dawley rats through a middle artery occlusion (MCAO) model. tDCS treatment began 24 h after MCAO and lasts for 6 consecutive days. Evaluate neurobehavioral deficits through an improved Neurological Severity Score (mNSS), Western blot, immunofluorescence staining, TUNEL staining, transmission electron microscopy (TEM), and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the expression of pyroptosis related proteins, cell morphology, and levels of inflammatory factors. The results showed that tDCS markedly reduced the levels of NLRP3 inflammasome-dependent pyroptosis proteins (NLRP3, ASC, cleaved-Caspase-1, and GSDMD-N), accompanied by a reduction in the number of cell membrane perforation and cell death related to pyroptosis. Moreover, tDCS increased the expression of NTN-1, which inhibited the activation of NLRP3 inflammasome through the peroxisome proliferator-activated receptor gamma (PPAR-γ)/nuclear factor kappa-B (NF-κB) signaling pathway. Knockdown of NTN-1 reversed the anti-pyroptosis and neuroprotective effect of tDCS. In conclusion, tDCS exerted neuroprotection by curbing neuronal pyroptosis through the NTN-1-mediated PPAR-γ/NF- κB pathway, and could be a useful strategy for ischemic stroke recovery.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106041"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923014","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":"In vitro pharmacological activity of twenty-eight synthetic cannabinoid receptor agonists at the type 1 and 2 cannabinoid receptors","authors":"Gabrielle Mercier ,&nbsp;Kawthar A. Mohamed ,&nbsp;Ayat Zagzoog ,&nbsp;Laura Cropper ,&nbsp;Brendan Ritchie ,&nbsp;Zhiyun Jin ,&nbsp;Mikin Patel ,&nbsp;Robert B. Laprairie","doi":"10.1016/j.neuint.2025.106039","DOIUrl":"10.1016/j.neuint.2025.106039","url":null,"abstract":"<div><div>Synthetic cannabinoid receptor agonists (SCRAs) are a class of novel psychoactive substances whose prevalence in illegal markets continues to grow. Δ⁹-tetrahydrocannabinol (THC) is the primary intoxicating compound present in cannabis and is well-known to behave as a partial agonist at both the type 1 and 2 cannabinoid receptors (CB1R, CB2R). Unlike THC, the SCRAs characterized to date generally behave as CB1R and/or CB2R full agonists. The high potency and full agonism of these ligands are thought to drive the toxicity of SCRAs, including psychoses, emesis, and tachycardia. In this study, twenty-eight compounds (including the reference ligands CP55,940 and THC) were evaluated for binding affinity, Gi protein-dependent inhibition of cAMP, and βarrestin2 recruitment in Chinese hamster ovary (CHO–K1) cells stably expressing either receptor. Radioligand binding results demonstrate a general lack of selectivity between cannabinoid receptor subtypes. In signaling assays, most compounds displayed the anticipated full agonism with low nanomolar potency characteristic of SCRAs. Many compounds displayed bias for the inhibition of cAMP over the recruitment of βarrestin2, and this was especially true at CB2R, where several compounds were inactive in the βarrestin2 recruitment assay. However, no clear structure-activity relationship emerged among the tested SCRAs that could account for their selectivity, potency, efficacy, or bias, although potential patterns are discussed herein. Overall, our data support growing evidence that the cannabinoid receptors accommodate a diverse range of ligands, and that compound function may be dictated by factors that are not yet well characterized, such as binding kinetics.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106039"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917409","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 potential of mulberry (Morus alba L.) leaf extract against pro-aggregant tau-mediated inflammation and mitochondrial dysfunction","authors":"Te-Hsien Lin ,&nbsp;Pei-Hsuan Tseng ,&nbsp;I-Cheng Chen ,&nbsp;Chung-Yin Lin ,&nbsp;Ming-Chung Lee ,&nbsp;Kuo-Hsuan Chang ,&nbsp;Guey-Jen Lee-Chen ,&nbsp;Chiung-Mei Chen","doi":"10.1016/j.neuint.2025.106042","DOIUrl":"10.1016/j.neuint.2025.106042","url":null,"abstract":"<div><div>In Alzheimer's disease (AD), Tau aggregates trigger microglial activation to release inflammatory factors and cause mitochondrial dysfunction, oxidative stress, and neuronal damage. With abundant potent antioxidants, mulberry (<em>Morus alba</em> L.) leaf extract has the potential to treat diseases associated with neuroinflammation, mitochondrial dysfunction, and oxidative stress. This study examined the neuroprotective effects of a mulberry leaf extract against pro-aggregant Tau-mediated inflammation and mitochondrial dysfunction in SH-SY5Y cells expressing the ΔK280 Tau repeat domain (Tau_RD). His-tagged ΔK280 Tau_RD fibrils prepared from <em>E. coli</em> activated BV-2 microglia, as revealed by their altered morphology, increased nitric oxide production, and elevated ionized calcium binding adaptor molecule 1 (IBA1) and major histocompatibility complex 2 (MHCII) expression. The mulberry leaf extract suppressed the production of pro-inflammatory mediators, including NO, IL-1β, IL-6, and TNF-α, and the expression of NLR family pyrin domain-containing 3 (NLRP3) and caspase-1 (CASP1) in ΔK280 Tau_RD fibril-stimulated BV-2 cells. Application of conditioned media collected from ΔK280 Tau_RD fibril-activated BV-2 cells induced cellular inflammation in ΔK280 Tau_RD-DsRed-expressing SH-SY5Y cells. The mulberry leaf extract protected these cells by suppressing lactate dehydrogenase (LDH) release, caspase-3 activity, NLR family pyrin domain-containing 1 (NLRP1), CASP1, IL-1β, IL-6, TNF-α, and reactive oxygen species as well as by enhancing neurite outgrowth. In addition, mulberry leaf extract increased mitochondrial membrane potential, lowered mitochondrial superoxide levels, and increased superoxide dismutase 2 (SOD2), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), and nuclear factor erythroid 2-related factor 2 (NRF2) levels in SH-SY5Y cells. In conclusion, mulberry leaf extract displayed neuroprotective effects by exerting anti-inflammatory and antioxidative activities to ameliorate pathological Tau-mediated mitochondrial dysfunction in a human Tau cell model. The results of this study support the notion that the mulberry leaf extract is a potential disease-modifying therapeutic agent for <span>AD</span>.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106042"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907678","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}