Journal of Neuroscience Research最新文献

{"title":"Angiotensin-II Type 1 and Type 2 Receptors Differentially Regulate TWIK1 Potassium Channel Expression in Wistar Rat Sensory Neurons","authors":"Emanuel David Peralta,&nbsp;Sergio Gonzalo Benitez,&nbsp;Yanaysis Stable García,&nbsp;Cristian Gabriel Acosta","doi":"10.1002/jnr.70127","DOIUrl":"10.1002/jnr.70127","url":null,"abstract":"<div>\u0000 \u0000 <p>Two-pore domain potassium (K2P) channels control resting membrane potential of neurons and contribute to pain hypersensitivity when their expression or function is reduced. Tandem of P-domains in a Weak Inwardly rectifying K⁺ channel 1 (TWIK1) is broadly expressed in the nervous system, yet little is known about its regulation in dorsal root ganglion (DRG) neurons. Because components of the renin–angiotensin system (RAS) modulate sensory excitability, we investigated whether Angiotensin-II (Ang II) and its receptors, AT1R and AT2R, regulate TWIK1 expression. Using primary DRG cultures, we found that Ang II significantly increased TWIK1 mRNA and protein at 1–2 days in vitro. Quantitative immunocytochemistry revealed receptor-specific effects: TWIK1 up-regulation at 1 day was primarily AT2R-dependent, whereas AT1R contributed to a lesser extent. TWIK1 expression declined by 2 days but remained sensitive to receptor blockade. To test physiological relevance, we injected Ang II intradermally into the hindpaw of adult rats. Repeated—but not single—Ang II injections produced a modest reduction of TWIK1 in large L5 DRG neurons and in NF200-positive cutaneous terminals. This decrease was accompanied by mild mechanical hypersensitivity without changes in cold sensitivity. These in vivo effects align with preferential AT1R expression in medium and large DRG neurons and with the in vitro finding that TWIK1 down-regulation is most evident when AT1R remains active. These results identify TWIK1 as a downstream target of Ang II signaling in sensory neurons and suggest that RAS-dependent modulation of K2P channels may influence neuronal excitability and contribute to pain-related processes.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645664","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 “Zinc Deficiency and Supplementation in Autism Spectrum Disorder and Phelan-McDermid Syndrome”","authors":"","doi":"10.1002/jnr.70128","DOIUrl":"10.1002/jnr.70128","url":null,"abstract":"<p>Alsufiani, H. M., A. S. Alkhanbashi, N. A. Bin Laswad, et al. 2022. “Zinc Deficiency and Supplementation in Autism Spectrum Disorder and Phelan-McDermid Syndrome.” <i>Journal of Neuroscience Research</i> 100, no. 4: 970–978. https://doi.org/10.1002/jnr.25019.</p><p>In the original published article, an error was identified in the reported prevalence of autism spectrum disorder (ASD).</p><p>In both the <b>Abstract</b> (“Approximately 1 in 36 children are diagnosed with autism spectrum disorder (ASD)”) and the <b>first paragraph of the Introduction</b> (“Around one in 36 children are diagnosed with autism, and it is four times more common in males than in females”), the prevalence was incorrectly stated as <b>1 in 36</b>.</p><p>The correct prevalence, based on the cited data, is <b>1 in 59</b>.</p><p>We apologize for this error.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627938","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":"The Transcription Factors Six3 and Six6 in Neuromedin-S Neurons Differentially Affect Circadian Rhythms","authors":"Brooke M. Van Loh,&nbsp;Geneva A. Dunn,&nbsp;Lauren E. Chun,&nbsp;Meera M. Patel,&nbsp;Nay Chi P. Naing,&nbsp;Duong Nguyen,&nbsp;Alexandra M. Yaw,&nbsp;Michael R. Gorman,&nbsp;Jessica Cassin,&nbsp;Pamela L. Mellon,&nbsp;Hanne M. Hoffmann,&nbsp;Karen J. Tonsfeldt","doi":"10.1002/jnr.70123","DOIUrl":"10.1002/jnr.70123","url":null,"abstract":"<p>Circadian rhythms are ~24-h rhythms generated by the suprachiasmatic nucleus (SCN) in the mammalian hypothalamus. The regulation of circadian rhythms and downstream processes is highly dependent on the proper development and function of the SCN. <i>Six3</i> and <i>Six6</i> are homologous homeodomain transcription factors that have been shown to be required for SCN development; intriguingly, both <i>Six3</i> and <i>Six6</i> remain expressed in the adult SCN. To determine the role of <i>Six3</i> and <i>Six6</i> in the SCN after neurogenesis, we used Cre-lox to conditionally knockdown either <i>Six3</i> or <i>Six6</i> from cells that express neuromedin-S (NMS), a neuropeptide expressed in approximately half of SCN neurons. We found that the <i>Nms</i>^<i>cre</i> allele turns on in the SCN after embryonic Day 16.5, limiting Cre-lox-mediated loss of <i>Six3</i> or <i>Six6</i> to the period after SCN neurogenesis. Using this approach, we hypothesized that <i>Six3</i> and <i>Six6</i> in NMS neurons regulate SCN circadian output and resulting reproductive function in males and females. Loss of <i>Six6</i> from NMS neurons had no impact on puberty and reproduction. While loss of <i>Six3</i> from NMS neurons had no effect in females, we found significantly decreased sperm motility in males, potentially through direct effects of <i>Six3</i> in the testis. Loss of <i>Six3,</i> but not <i>Six6</i>, in NMS neurons resulted in shortened wheel-running periods in constant darkness, indicating a shortening of the endogenous rhythm within the SCN. Together, these data indicate a role of <i>Six3</i> in determining the circadian period, suggesting differing functions of <i>Six3</i> and <i>Six6</i> in the adult SCN.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623180","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":"Acute Opioid Receptor Blockade Restores Vascular Endothelial Growth Factor and Astrocyte Response in db/db Mouse Brain Following Hypoxia-Ischemic Injury","authors":"Rashmi Kumari,&nbsp;Elizabeth A. Proctor,&nbsp;Patricia McLaughlin","doi":"10.1002/jnr.70125","DOIUrl":"10.1002/jnr.70125","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes plays an important role in the pathogenesis of ischemic stroke and brain recovery. We have reported the neuroprotective effect of low dose naltrexone (LDN) in type 2 diabetic (<i>db/db)</i> mice post-hypoxia-ischemia (HI) injury. In this study, we explored LDN mediated mechanisms of neuroprotection in diabetic mice. Adult male <i>db/db</i> and non-diabetic (<i>db/+)</i> mice underwent right common carotid artery occlusion followed by hypoxia (8% O₂) for 20 min. LDN (1 mg/kg) was administered at 4, 24, and 48 h post-HI, and mice were euthanized at 72 h. Blood and brain tissue were analyzed for cytokines and growth factors by multiplex array, immunofluorescence and western blotting. LDN treatment resulted in an increased number of reactive astrocytes in the motor cortex and caudate and hippocampus of diabetic mice, which was decreased in <i>db/+</i> mice, except in the CA3 hippocampal region. LDN did not show any significant change in the cytokine response between <i>db/+</i> and <i>db/db</i> mice. However, the vascular endothelial growth factor (VEGF) levels in the plasma and brain tissue of LDN-treated <i>db/db</i> mice that were significantly reduced in the vehicle-treated <i>db/db</i> group were restored to the level of the <i>db/+</i> treated group. When infarct size was categorized, LDN increased VEGF+ neurons in the motor cortex and caudate in small infarcts, and in the motor cortex of large infarcts, in <i>db/db</i> mice. The study suggests that acute LDN increased the number of VEGF+ neurons and prevented astrocytic cell death in <i>db/db</i> mice, thus enhancing neuroprotection following brain HI injury.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609233","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":"Age and Maturation Stage Linked Consequences of Fibrinogen on Human Oligodendroglia","authors":"Gabriela J. Blaszczyk,&nbsp;Chao Weng,&nbsp;Abdulshakour Mohammadnia,&nbsp;Qiao-Ling Cui,&nbsp;Arianna Giurleo,&nbsp;Adam M. R. Groh,&nbsp;Chloe Plouffe,&nbsp;Julien Sirois,&nbsp;Valerio E. C. Piscopo,&nbsp;Moein Yaqubi,&nbsp;Asad Taqvi,&nbsp;Erin Cassidy,&nbsp;Liam Callahan Martin,&nbsp;Jeffery A. Hall,&nbsp;Roy W. R. Dudley,&nbsp;Myriam Srour,&nbsp;Stephanie E. J. Zandee,&nbsp;Wendy Klement,&nbsp;Sandra Larouche,&nbsp;Alexandre Prat,&nbsp;Thomas M. Durcan,&nbsp;Jo Anne Stratton,&nbsp;Jack P. Antel,&nbsp;G. R. Wayne Moore","doi":"10.1002/jnr.70120","DOIUrl":"10.1002/jnr.70120","url":null,"abstract":"<p>Fibrinogen is a blood-derived protein involved in coagulation and can make its way into the central nervous system (CNS) following breakdown of the blood–brain barrier. This molecule has been implicated in multiple sclerosis (MS), a disease marked by inflammation and demyelination in the CNS. However, the effect of this molecule has not been studied on human myelinating cells. This study examines how fibrinogen influences human oligodendrocyte (OL) lineage cells at various stages of development. Using induced pluripotent stem cell-derived (iPSC) OL precursors and human primary OLs, we examined the effects of fibrinogen on cell differentiation, viability, and myelination-related function. Here we show the differential effect of fibrinogen, based on OL-lineage stage. While fibrinogen induced aberrant differentiation of early lineage OLs, by inhibiting their maturation and inducing an astrocytic phenotype, on mature OLs fibrinogen was found to promote myelination capacity, as shown by ensheathment assays as well as on the RNA level. These effects were associated with the activation of bone morphogenetic protein (BMP) signaling, both in early and mature OLs. We further found BMP signaling enrichment in OLs to be correlated with the inflammatory activity of an MS lesion and confirmed fibrinogen deposition on OLs in situ. Unlike previous rodent studies, these findings indicate that fibrinogen has a lineage-dependent effect, where it may be inhibitory earlier in the lineage while promoting OL function in later stages. Understanding this dual role will provide insight into remyelination failure in MS and highlights the importance of timing and target in future therapeutic strategies.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499184","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":"Correction to “Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain”","authors":"","doi":"10.1002/jnr.70122","DOIUrl":"10.1002/jnr.70122","url":null,"abstract":"<p>Nazli, D., D. Ipekgil, Y. K. Poyraz, et al. 2026. “Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain.” <i>Journal of Neuroscience Research</i> 104, no. 2: e70119. https://doi.org/10.1002/jnr.70119.</p><p>After publication, we identified that the final images (top and bottom) in Figure 3A and the final images (top and bottom) in Figure 6A were identical. Upon reexamining the original data files, we determined that this duplication occurred inadvertently during the revision process while incorporating the Donepezil data. Specifically, the correct <span>l</span>-plastin image intended for Figure 6A was not uploaded, and an image from Figure 3A was mistakenly duplicated in its place.</p><p>We apologize for this error.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433523","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":"Chondroitin Sulfate Proteoglycans in CNS Development and Pathophysiology","authors":"Seyed Mojtaba Hosseini,&nbsp;Soheila Karimi-Abdolrezaee","doi":"10.1002/jnr.70115","DOIUrl":"10.1002/jnr.70115","url":null,"abstract":"<p>Chondroitin sulfate proteoglycans (CSPGs) are major components of the matrix in many tissues including the central nervous system (CNS). Interactions between extracellular CSPGs and different cell types are crucial for the development of the CNS as CSPGs are heavily involved in maintaining the pool of progenitors, neurogenesis, neuronal migration and maturation, cortical lamination, synapse formation and stabilization, neuronal plasticity, and memory formation. CSPGs play distinct roles in CNS development and pathology. While physiologic levels of CSPGs have key roles in CNS development, CNS pathologies result in upregulation of CSPGs that pose a barrier to neuroregeneration. Extensive evidence shows that pathologic CSPGs interfere with various regenerative mechanisms including axonal elongation, immunomodulation, synaptogenesis, cellular replacement, and remyelination. At the cellular level, CSPGs' effects are mainly mediated through activation of leukocyte common antigen-related receptor (LAR) and protein tyrosine phosphatase sigma (PTP-σ) receptors. Various approaches have been developed to overcome the inhibitory effects of pathologic CSPGs including enzymatic degradation of CSPGs, blocking CSPG/LAR/PTP-σ axis, and inhibition of CSPGs synthesis. Here, we will discuss the current understanding on the role and mechanisms of CSPGs in CNS development and pathologies and signaling pathways that mediate CSPGs' effects in the CNS. We will also review how CSPGs have been modulated in neurological disorders.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317041","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":"RNAseq Analysis of the Cerebellum Reveals Significant Gene Dysregulation That May Explain Chronic Disease Progression in Mild Traumatic Brain Injury","authors":"Katy M. Li,&nbsp;Anna Balzer,&nbsp;Thomas M. Doering,&nbsp;Matthew I. Hiskens,&nbsp;Ryan du Preez,&nbsp;Andrew S. Fenning","doi":"10.1002/jnr.70105","DOIUrl":"10.1002/jnr.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>Mild traumatic brain injury (mTBI) is a major public health concern worldwide and contributes to chronic, persistent neurodegenerative diseases; however, the mechanisms are not fully understood. Most studies have examined cerebral cortex, hippocampus, and thalamus brain tissue, but the impact on the cerebellum following repetitive mTBI (rmTBI) leading to secondary injury cascades and long-term pathophysiology is largely unexplored. This study investigated changes in gene expression in cerebellum tissue from an established murine model of rmTBI. The cerebellum tissue from 15 male C57BL/6J mice was analyzed using RNA sequencing technology for animals sacrificed 48 h (acute) and 90 days (chronic) following a repetitive mild impact schedule. Differentially expressed gene (DEG) analysis showed no dysregulated genes above log2 fold change at 48 h, but 360 DEGs at 90 days. At 90 days, multiple Gene Ontologies were different to controls, including disruption to mitochondria, proteosomes, ribosomes, and a reduction in vital cellular energy processes. Kyoto Encyclopedia of Genes and Genomes pathway analysis in the chronic injury group revealed that dysregulated genes were characteristic of multiple neurological diseases, including <i>Parkinson's</i> and <i>Huntington's disease</i> genetic signatures. This data demonstrates that the cerebellum and other brain regions disparate from the site of impact are more than just a bystander in chronic neurodegenerative pathologies and provides a vital link to the development of neurological disorders like Parkinson's disease from rmTBI trauma.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220118","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":"Purkinje Cells as Gatekeepers of Seizure Susceptibility: Insights From Optogenetics","authors":"Sara Bernardi,&nbsp;Federica Gemignani,&nbsp;Filippo M. Santorelli,&nbsp;Maria Marchese","doi":"10.1002/jnr.70118","DOIUrl":"10.1002/jnr.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>Purkinje cells (PCs), the principal output neurons of the cerebellar cortex, are classically implicated in motor coordination via inhibitory projections to the deep cerebellar nuclei (DCN). Emerging evidence suggests their influence extends to seizure susceptibility, yet the underlying mechanisms remain unclear. Here, we investigated the functional role of PCs in locomotion and seizure-like activity in zebrafish larvae. Using the UAS/Gal4 system, we selectively expressed light-sensitive ion channels in PCs: Channelrhodopsin-2 (ChR2) to activate, and Anion ChannelRhodopsin-2 (ACR2) to inhibit neuronal activity. Behavioral assays at 5 days post-fertilization assessed locomotor output, while local field potential recordings monitored seizure-like events under baseline conditions and following administration of a proconvulsant agent. Optogenetic activation of PCs transiently increased locomotion and significantly reduced the duration and power of seizure-like events under hyperexcitable conditions, without affecting baseline activity. Conversely, inhibition of PCs was sufficient to induce seizure-like activity even in the absence of convulsant stimuli. These results reveal a dual role for PCs: they suppress pathological hyperexcitability during proconvulsant states, yet their inhibition can trigger seizures. This work highlights the cerebellum as a critical regulator of excitation-inhibition balance, linking motor control and seizure susceptibility, and suggests that cerebellar dysfunction may contribute to both motor and epileptic phenotypes observed in neurodegenerative disorders.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165476","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":"Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain","authors":"Dilek Nazli,&nbsp;Dogac Ipekgil,&nbsp;Yusuf Kaan Poyraz,&nbsp;Kubilay Can,&nbsp;Ilke Okmen,&nbsp;Ebru Turhanlar-Sahin,&nbsp;Belgin Sert Serdar,&nbsp;Semra Kocturk,&nbsp;Gunes Ozhan","doi":"10.1002/jnr.70119","DOIUrl":"10.1002/jnr.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral alterations. The pathogenesis of AD involves the accumulation of amyloid-beta (Aβ) plaques and the hyperphosphorylated tau proteins, which disrupt neuronal function and trigger neuroinflammation. This study explores the therapeutic potential of epigallocatechin gallate (EGCG) and punicalagin (PU) in mitigating Aβ-induced toxicity using an adult zebrafish model of AD. Our results demonstrate that the EGCG + PU combination significantly reduces Aβ accumulation, protects against cellular damage, suppresses acetylcholinesterase (AChE) activity, and normalizes the expression of amyloidogenic and AD-related genes. Additionally, EGCG + PU treatment alleviates neuroinflammation by suppressing glial activation, including reductions in L-plastin and proinflammatory cytokine expression, while promoting neuronal recovery through mechanisms of neurogenesis and neuroprotection. Notably, the combination treatment restored neuronal density and improved behavioral outcomes by alleviating anxiety- and aggression-like behaviors associated with Aβ toxicity. These results underscore the synergistic neuroprotective effects of EGCG + PU, highlighting their potential as a novel therapeutic approach for mitigating the pathological, behavioral, and inflammatory aspects of AD.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165485","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}