Cellular and Molecular Neurobiology最新文献

{"title":"Postmortem Evidence of Lymphatic Vessels Located at the Boundary of Central and Peripheral Nervous Systems in the Cervical Spine.","authors":"Shalin S Bhatt, Caitlin R Coker, Lauren K Bagian, Carlo S Tornatore, Jayanti A Kulkarni, Jennifer H Um, Ethan T Weatherdon, Caroline R Hallowell, Alexandra M Akhtarzandi-Das, Marissa N Dreger-Tretheway, Alec J Casely, Emily V Deale, Sabrina F DeLeonibus, Henry Li, Julia S Hakeem, Shreya V Bhatt, Divpriya Talwar, Jeremiah O Olabosipo, Jacqueline M Caputo, Brent T Harris","doi":"10.1007/s10571-026-01744-4","DOIUrl":"10.1007/s10571-026-01744-4","url":null,"abstract":"<p><p>Recent modern characterizations of human meningeal lymphatic vessels have reframed long-standing views of central nervous system neurofluid drainage. However, gross anatomical data on lymphatic vessels remains sparse. In this cadaveric study, we combined dissections and immunohistochemical analysis in formalin-fixed human body donors to characterize lymphatic vessels associated with cervical spinal nerves. Using manual, low-pressure peroxide-dye injections via the thoracic duct and left jugular lymphatic trunk, we effervesced and identified candidate lymphatic pathways extending toward the head and neck, highlighting vessels accompanying cervical spinal nerves at the interface between the vertebral canal and surrounding soft tissues. Dye-identified vessels and adjacent dural and perineural tissues were harvested and processed for D2-40 immunohistochemistry, targeting the lymphatic endothelial marker podoplanin. Across four of nine donors, we observed D2-40-positive, thin-walled luminal structures within epineurial and peridural compartments at the craniovertebral junction, along cervical intervertebral foramina, and near brachial plexus roots, consistent with lymphatic vessels. These findings identify D2-40-positive vessel profiles consistent with lymphatic vasculature extending along spinal nerves without directly demonstrating intradural channels or cerebrospinal fluid outflow. They provide an anatomical framework for future studies probing how cervical lymphatic networks at CNS interfaces contribute to neurofluid drainage, immune cell trafficking, and neurological disease.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABA_A Receptors and Drug-Resistant Epilepsy: Why It's Time to Think Outside the Pore.","authors":"Iman Imtiyaz Ahmed Juvale, Alina Arulsamy","doi":"10.1007/s10571-026-01759-x","DOIUrl":"10.1007/s10571-026-01759-x","url":null,"abstract":"<p><p>Drug-resistant epilepsy (DRE) represents a major clinical hazard, characterised by persistent uncontrolled seizures that elevate risks of trauma, cognitive deterioration, psychiatric comorbidity, and sudden unexpected death in epilepsy, while cumulative medication exposure, healthcare burden, and functional impairment substantially worsen long-term morbidity and quality of life. In DRE, disruptions in GABA_A receptors (GABA_AR) function through altered subunit composition, receptor mislocalisation, or impaired trafficking, undermine inhibitory control and contribute to persistent seizures. The regulation of intracellular chloride by NKCC1 and KCC2 further shapes GABA_AR-mediated inhibition, where imbalances in these transporters exacerbate network hyperexcitability. Structural studies, including high-resolution cryo-EM, reveal how ligand binding, receptor conformation, and interactions with auxiliary proteins modulate GABA_AR activity, offering insights into why some subtypes respond differently to benzodiazepines or neurosteroids. Emerging evidence suggests that targeting receptor-associated proteins, trafficking pathways, or specific subunit combinations may offer novel ways to restore inhibitory tone and overcome pharmacoresistance. Understanding how these molecular, structural, and cellular factors converge to alter GABA_AR function provides a roadmap for designing therapies that are both effective and precise, especially for DRE. By unravelling the mechanisms behind GABA_AR dysfunction in DRE, new avenues open for restoring network stability and improving outcomes for patients living with DRE.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neurotrophin Receptor TrkC Contributes to the Development of Diverse Olfactory Bulb Neurons.","authors":"Katarzyna Bartkowska, Anna Filipek, Ruzanna Djavadian","doi":"10.1007/s10571-026-01757-z","DOIUrl":"10.1007/s10571-026-01757-z","url":null,"abstract":"<p><p>In mammals, expression of the neurotrophin receptor TrkC begins during early brain development and is present in almost all brain structures. In the olfactory bulb, TrkC expression appears with the generation of the first neurons. Here, we examine the role of TrkC receptors in the development of distinct olfactory bulb cell types in the opossum Monodelphis domestica. We determine that mitral/tufted projecting cells are generated on postnatal days (P) 1-5 and later, starting at P11, periglomerular and granule interneurons are developed. We found that TrkC signaling has no effect on the proliferation of early- and later-born neurons, but has a cell-specific effect on the growth of distinct olfactory bulb cells. Silencing of TrkC expression by shRNA affects the morphometric characteristics of projecting cells. Altogether, our findings show that TrkC signaling contributes to maintaining soma growth and dendritic complexity of projecting mitral/tufted neurons of the olfactory bulb.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-25-3p Inhibition Sensitizes Patient-Derived Glioblastoma Cells to Temozolomide via β-catenin Downregulation.","authors":"Katharina Richter, Hannah Markmann, Philipp Kaps, Annabell Wolff, Stefan Simm, Daniel Dubinski, Florian Gessler, Thomas M Freiman, Timo Kirschstein, Christian Junghanss, Claudia Maletzki, Bjoern Schneider","doi":"10.1007/s10571-026-01750-6","DOIUrl":"10.1007/s10571-026-01750-6","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) play pivotal roles in glioblastoma (GBM) progression and therapy resistance. Among them, miR-25-3p has emerged as a key oncogenic miRNA that promotes tumor growth, invasiveness, and resistance to temozolomide (TMZ). In this study, we profiled miRNA expression in primary GBM specimens (n = 50) stratified by MGMT methylation and TP53 mutation status and assessed the functional impact of miR-25-3p inhibition in seven patient-derived GBM cell lines. Quantitative PCR analysis revealed upregulation of miR-135b in MGMT-methylated tumors and miR-10b in TP53-mutant cases. Both miR-25-3p and miR-10b were significantly elevated in 3D spheroid cultures compared to 2D monolayers. Notably, both miRNAs were secreted via tumor-derived extracellular vesicles, implicating a role in cell-cell communication. Inhibition of miR-25-3p in GBM cell lines consistently suppressed β-catenin and re-induced FBXW7 expression across all cases, correlating with inhibitor uptake. In four of seven cell lines, miR-25-3p inhibition enhanced TMZ sensitivity and reduced invasiveness, although the anti-invasive effect was not further potentiated by the addition of TMZ. In addition, RNA-Seq and methylome analyses revealed genetic and epigenetic reprograming toward a less aggressive, less invasive phenotype with reduced stemness potential. These findings highlight the interplay between tumor microenvironment and molecular heterogeneity in shaping miRNA dynamics in GBM. Collectively, our results identify miR-25-3p as a promising dual-action therapeutic target to mitigating both invasion and chemoresistance in GBM, warranting further translational investigation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"46 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148100954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strain-Dependent Differences in Baseline Retinal Immune Homeostasis: A Comparative Study of Albino and Pigmented Mice.","authors":"Miguel A Martínez-López, Víctor Paleo-García, Sara Rubio-Casado, José A Fernández-Albarral, José A Matamoros, Juan J Salazar, Ana I Ramírez, Eva M Marco, Meritxell López-Gallardo","doi":"10.1007/s10571-026-01755-1","DOIUrl":"10.1007/s10571-026-01755-1","url":null,"abstract":"<p><p>Mouse models are essential for glaucoma research; however, strain-dependent biological differences may complicate the interpretation and translational value of experimental findings. Because baseline retinal immune tone can shape the response to ocular hypertension (OHT), defining constitutive inflammatory profiles across commonly used mouse strains is critical. Basal intraocular pressure (IOP), retinal interleukin (IL)-1β, interferon gamma (IFN-γ), IL-6, IL-4, IL-10, and vascular endothelial growth factor (VEGF) levels by Luminex xMAP, and the cellular localization of inflammatory mediators by immunofluorescence using Iba-1, GFAP, Brn3a, NF-200, and VEGFR1 were compared between male albino Swiss CD1 and pigmented C57BL/6J mice. Basal IOP did not differ between strains, whereas the basal retinal immune environment did. CD1 mice showed higher IL-1β and IL-4 levels and detectable IFN-γ, whereas C57BL/6J mice showed higher IL-6, IL-10, and VEGF levels. Immunofluorescence revealed strain-specific localization: in CD1 retinas, IL-1β was detected in microglia and macroglia, IFN-γ in microglia, and IL-6 mainly in microglia; in C57BL/6J retinas, IL-1β and IL-6 were mainly associated with macroglia (Müller cells and astrocytes), and IL-4 with microglia. In both strains, IL-10 localized to NF-200-positive axons and VEGFR1 to glial fibrillary acidic protein (GFAP)-positive macroglia. Despite similar basal IOP, albino Swiss CD1 and pigmented C57BL/6J mice differ markedly in their basal retinal immune profiles. Albino mice show a more reactive baseline state, whereas pigmented mice display tighter immunoregulation and stronger immune-vascular support. Strain selection is therefore critical for experimental design, data interpretation, and translational relevance to ensure preclinical findings translate into human outcomes.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of Hippocampal Synaptic Plasticity Disruption Induced by Chronic Methamphetamine Exposure: A Narrative Review.","authors":"Mahdiyeh Hedayati-Moghadam, Fateme Razazpour, Zohreh Hakemi, Fateme Khani, Yousef Baghcheghi","doi":"10.1007/s10571-026-01747-1","DOIUrl":"10.1007/s10571-026-01747-1","url":null,"abstract":"<p><p>Chronic methamphetamine (Meth) abuse represents a significant global public health crisis, characterized by profound and often persistent cognitive deficits, particularly in hippocampal-dependent memory and learning. This narrative review synthesizes current evidence on the molecular mechanisms through which chronic Meth exposure disrupts hippocampal synaptic plasticity, ultimately driving cognitive impairment. We establish that the initiating event involves Meth-induced dysregulation of dopaminergic signaling, primarily through dopamine transporter (DAT) inhibition, leading to sustained extracellular dopamine surges. This dopamine excess triggers a pathogenic cascade dominated by three interconnected processes: (1) pronounced oxidative stress via dopamine auto-oxidation and mitochondrial dysfunction, generating reactive oxygen species (ROS) that damage synaptic components; (2) mitochondrial apoptotic activation through p53-Bax signaling, cytochrome c release, and caspase-3-mediated cleavage of synaptic scaffolding proteins (e.g., PSD-95, ARC); and (3) suppression of neurotrophic support via BDNF-TrkB-PI3K/Akt pathway impairment, compounded by glutamate receptor dysregulation (NMDAR internalization, AMPAR trafficking defects). These mechanisms converge to induce structural synaptic pathology-including dendritic spine loss (notably mature mushroom spines in dentate gyrus), presynaptic vesicle depletion, and postsynaptic density disintegration-and functional deficits in LTP and LTD. Critically, these processes are amplified by neuroinflammation (microglial TNF-α/IL-1β release) and epigenetic dysregulation (HDAC2 upregulation, BDNF promoter methylation), creating a self-sustaining cycle of synaptic injury. Preclinical and clinical evidence consistently links these molecular disruptions to measurable cognitive decline, including impaired spatial navigation, pattern separation, and declarative memory. Therapeutic strategies targeting key nodes of this cascade show significant promise: dopamine stabilizers (e.g., aripiprazole) normalize D1/D2 receptor imbalance; anti-apoptotics (e.g., minocycline, resveratrol) inhibit caspase-3 and p53; neurotrophic agents (TrkB agonists, BDNF mimetics) restore synaptic protein synthesis; and antioxidants (e.g., N-acetylcysteine) counteract ROS. Future research must address critical gaps in understanding sex-specific vulnerabilities, circuit-selective susceptibility (e.g., hippocampal-VTA loops), and the role of stable epigenetic modifications in sustaining cognitive deficits. Advancing multi-target therapeutic approaches aligned with the temporal progression of Meth neurotoxicity offers the best hope for reversing synaptic dysfunction and mitigating the enduring cognitive burden of Meth addiction.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S3I-201, a STAT3 Inhibitor, Inhibits Proinflammatory Mediator Signalling in CD19 and CD45R/B220 Cells in a Mouse Model of Multiple Sclerosis.","authors":"Abdulaziz M S Alsaad, Ahmed Nadeem, Sabry M Attia, Mushtaq A Ansari, Saleh A Bakheet, Majed Ali Algonaiah, Haneen A Al-Mazroua, Hatun A Alomar, Wedad S Sarawi, Mohammed M Almutairi, Abdullah A Aldossari, Quaiser Saquib, Norah K Algarzae, Mohamed A Mahmoud, Marwa H Hussein, Sheikh F Ahmad","doi":"10.1007/s10571-026-01751-5","DOIUrl":"10.1007/s10571-026-01751-5","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic illness characterised by progressive central nervous system (CNS) degeneration. The efficacy of most current MS medicines is limited, and significant adverse effects remain a concern. STAT3 inhibitors show potential for treating several immunological diseases. The current study demonstrates that S3I-201, a well-established STAT3 inhibitor, effectively treats PLP_139-151-induced EAE in SJL/J mice. After establishing EAE, mice were administered S3I-201 intraperitoneally (10 mg/kg) daily from day 14 through day 35. Flow cytometry was used to measure the effect of S3I-201 on the expression levels of IL-6, iNOS, Notch1, Notch3, GM-CSF, and NF-κB p65 in CD19⁺ and CD45R/B220⁺ B cells. RT-PCR was also used to study the effect of S3I-201 on the mRNA expression levels of IL-6, iNOS, Notch1, Notch3, GM-CSF, and NF-κB p65 in brain tissue. S3I-201 administration reduced the number of CD19⁺IL-6⁺, CD45R⁺IL-6⁺, CD19⁺iNOS⁺, CD45R⁺iNOS⁺, CD19⁺Notch1⁺, CD45R⁺Notch3⁺, CD19⁺GM-CSF⁺, CD45R⁺GM-CSF⁺, CD19⁺NF-κB p65⁺, and CD45R⁺NF-κB p65⁺ cells in EAE mice. Furthermore, S3I-201 administration reduced the expression of IL-6, iNOS, Notch1, Notch3, GM-CSF, and NF-κB p65 mRNA in brain tissue. S3I-201 inhibits the signalling of inflammatory mediators via various cellular pathways. Our findings suggest that S3I-201 may have therapeutic effects on EAE and may slow its progression in MS.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nyap1 Redirects JNK Signaling to Couple Neuroprotection with Circuit Regeneration After Spinal Cord Injury.","authors":"Wenyuan Li, Yi Li, Yong Liu, Xiaoya Wang, Feng Ji, Jinying Hu, Yingying Shen, Zhihan Guo, Xiumei Fu, Ying Wang","doi":"10.1007/s10571-026-01749-z","DOIUrl":"10.1007/s10571-026-01749-z","url":null,"abstract":"<p><p>Spinal cord injury (SCI) causes permanent motor deficits primarily due to neuronal apoptosis and inadequate axonal regeneration, with the c-Jun N-terminal kinase (JNK)/c-Jun pathway playing a dual role in neurodegeneration and regeneration. Here, we identified Nyap1 as a spatiotemporally limited modulator that rearranges JNK signaling to shift its function from degeneration to regeneration. Time-resolved transcriptomic profiling showed Nyap1 was dynamically upregulated as a hub gene during the acute-to-subacute phase of SCI. Nyap1 was associated with altered subcellular distribution of p-JNK, with increased cytoplasmic retention, with overexpression enriching p-JNK in the cytosol and limiting nuclear translocation-sufficient to drive regenerative transcription without inducing apoptosis. This interaction was associated with modulation of apoptosis-related and regeneration-related signaling, including changes in the Bcl-2/Bax ratio, caspase-3 activation, c-Jun phosphorylation, and GAP43 expression, with these effects abrogated by JNK inhibition. In vivo, Nyap1 overexpression preserved thoracic spinal motor neurons, promoted descending propriospinal tract (DPST) axonal regeneration, enhanced lumbar motor neuron dendritic arborization and synaptic input, and reduced lesion cavity volume. These structural improvements were accompanied by better gait coordination, neuromuscular reinnervation, and translesional motor conduction. Our findings support a model in which Nyap1 is associated with spatial redistribution of p-JNK-related signaling, linking neuronal survival with circuit-level plasticity after SCI, highlighting its potential as a therapeutic candidate for CNS trauma.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble Fiber Intake Restores the Estrous Cycle and Sex Hormone Alterations in APP/PS1 Female Mice.","authors":"Ivonne Sagrario Romero-Flores, Daniel Cuervo-Zanatta, Roberto Chavira, Vicente Sánchez-Valle, Jaime García-Mena, Claudia Perez-Cruz","doi":"10.1007/s10571-026-01745-3","DOIUrl":"10.1007/s10571-026-01745-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common form of dementia, with a higher prevalence in women than in men. It has been suggested that the decline in estrogen production after menopause may increase the risk of developing dementia. We have previously shown that transgenic female APP/PS1 mice, overexpressing APP and PS1 proteins, develop spontaneous gut dysbiosis with a consequent dysfunctional estrobolome leading to higher estradiol excretion rate compared to age-matched wildtype (WT) females. It has been demonstrated that soluble fiber intake restores gut microbiota dysbiosis, reduces anxiety and improves cognitive function in APP/PS1 male mice. Therefore, the aim of this study was to evaluate if the intake of soluble fiber can modify the gut microbiota composition, alleviating the estrobolome dysfunction, and restoring sex-hormone alterations in female APP/PS1 mice. We confirm that six-month-old APP/PS1 female mice develop a spontaneous gut dysbiosis, an estrobolome dysfunction, and lower oestrous cycle frequencies than their WT littermates. Soluble fiber intake modulates the gut microbiota composition and increases beta-glucuronidase activity in faecal samples associated with a restoration of estradiol and DHEA plasma levels. Additionally, consuming soluble fiber affects various bacterial metabolic pathways and enhances the production of butyrate and acetate. Improved memory and cognitive performance were also observed in female APP/PS1 mice that were fed fructans. Therefore, soluble fiber intake may represent a preventive strategy to mitigate the alterations associated with the onset of reproductive senescence and dementia in females.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Purine Metabolism During Differentiation of Dopamine Neurons from Human Induced Pluripotent Stem Cells.","authors":"Lauren Grychowski, Fatemeh Seifar, Erkin Ozel, Anika Thite, Diane J Sutcliffe, Ashok R Dinasarapu, Ellen J Hess, H A Jinnah","doi":"10.1007/s10571-026-01734-6","DOIUrl":"10.1007/s10571-026-01734-6","url":null,"abstract":"<p><p>Purines are a class of ubiquitous molecules required for fundamental processes in all cells. Purines are derived from two major sources: de novo synthesis, and salvage of preformed purine bases. The current studies provide evidence that the relative contributions of these two pathways change substantially as human induced pluripotent stem cells (iPSCs) differentiate into neurons. Expression of all genes in the de novo synthesis pathway decreases as pluripotent cells differentiate into neurons, but expression of the salvage pathway gene HPRT1 increases. This selective rise in HPRT1 gene expression corresponds with increased activity of its associated enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). Similar changes in the expression of genes for the de novo pathway genes and for HPRT1 were found in a public database of gene expression for human brain development. The consequences of eliminating HGprt-mediated recycling were also evaluated in human-derived iPSCs with null HPRT1 mutations and stock iPSC lines that have been gene-edited to contain a null HPRT1 mutation. The absence of HGprt had no apparent impact on early neuronal differentiation, through 60 days of in vitro differentiation. Biochemical studies of purine content showed that that the absence of HGprt had little impact on intracellular purines, although large amounts of its substrate (hypoxanthine) accumulated in the tissue culture medium. Neurons derived from iPSCs without HGprt appeared morphologically and neurochemically indistinguishable from neurons derived from iPSCs where HGprt was intact. Interrogation of the transcriptome using RNA sequencing (RNAseq) indicated that the absence of HGprt had no consistent impact on gene expression during differentiation. Overall, these results suggest HGprt does not have a large impact on early neuronal differentiation and may instead play a more important role in later neuronal differentiation or function.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}