Journal of Neurochemistry最新文献

{"title":"Modulation of pTau181 by Glypican-1-Derived Heparan Sulfate in Human Neural Progenitor Cells and ApoE4-Expressing Induced Neurons","authors":"Fang Cheng,&nbsp;Lars-Åke Fransson,&nbsp;Katrin Mani","doi":"10.1111/jnc.70162","DOIUrl":"https://doi.org/10.1111/jnc.70162","url":null,"abstract":"<p>In Alzheimer's disease (AD) there is accumulation of amyloid-β (Aβ) and hyperphosphorylated tau (pTau) in the brain. Aβ activates kinases that phosphorylate tau. Increased pTau181 is a signal for hyperphosphorylation of tau. The generation of Aβ from amyloid precursor protein (APP) and the release of heparan sulfate (HS) from the proteoglycan glypican-1 (GPC1) are interconnected. Release of HS is APP-, ascorbate-, copper-, and NO-dependent. HS-Aβ interactions may regulate tau phosphorylation in human neural stem cells (NSC). The most influential risk factor for sporadic AD is the presence of the ε4 allele of apolipoprotein E (ApoE). Here, we have further explored the interplay between GPC1-derived HS and pTau181 formation in human neural progenitor cells (NPC) and induced neurons (iN) obtained by reprogramming of human fibroblasts from ApoE3- and ApoE4-carriers. HS release from GPC1 was either suppressed or stimulated, and effects on pTau181 were monitored by immunofluorescence microscopy and quantified by intensity measurements as well as by enzyme-linked immunosorbent assay (ELISA) technique. Stimulation of HS release decreased pTau181 in NSC but was without effect in NPC, where tau was mostly in the nuclei. However, suppression of HS release in NPC increased pTau181. Stimulation of HS release decreased pTau181 in ApoE4/4-iN but not in ApoE3/3-iN. A high intake of vitamin C may be of prophylactic value in ApoE4-positive individuals.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647114","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 “The Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus”","authors":"","doi":"10.1111/jnc.70149","DOIUrl":"https://doi.org/10.1111/jnc.70149","url":null,"abstract":"<p>del Ángel, M., Tsutiya, A., Hayani, H., Madencioglu, D., Kul, E., Caliskan, G., Demiray, Y.E., Dityatev, A., and Stork, O. (2025). The Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus. <i>Journal of Neurochemistry</i>, 169: e70094. https://doi.org/10.1111/jnc.70094.</p><p>In the paper by del Ángel et al. (2025), the first author's name appeared incorrectly. The author's correct name is Miguel del Ángel.</p><p>The original paper has now been corrected.</p><p>We apologize for this error.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624813","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":"Exploring the Role of Microglial Cells in the Gut–Brain Axis Communication: A Systematic Review","authors":"Nadia Suyin Ortiz-Samur,&nbsp;Akshay Kumar Vijaya,&nbsp;Aurelijus Burokas,&nbsp;Virginia Mela","doi":"10.1111/jnc.70154","DOIUrl":"https://doi.org/10.1111/jnc.70154","url":null,"abstract":"<p>The gut–brain axis (GBA) is a bidirectional communication system between the gastrointestinal tract and the CNS, playing a key role in neurological function, immune response, and metabolism. Microglia, the resident immune cells in the brain, are crucial regulators of neuroinflammation and synaptic plasticity. Recent studies indicate that the gut microbiota modulates microglial activity through metabolic and immune pathways, with implications for neurodegenerative, neurodevelopmental, and psychiatric disorders. However, the mechanisms underlying microbiota–microglia interactions remain unclear. Following a systematic screening of 4481 studies, 20 preclinical studies met the inclusion criteria and were reviewed in depth to assess microbiota–microglia interactions. These studies were found by searching in PubMed, Science Direct, and Google Scholar. The findings synthesize results from 20 carefully selected studies examining the impact of gut microbiota on microglial function. Experimental models, including fecal microbiota transplantation, dietary interventions, and bacterial supplementation, were analyzed. Microglial activity was assessed through immunohistochemistry, gene expression profiling, and functional assays. Most studies suggest that gut dysbiosis promotes microglial overactivation and neuroinflammation through pathways involving microbial-derived short-chain fatty acids (SCFAs), bile acids, and neuroimmune signaling cascades such as TLR4/NF-κB and the NLRP3 inflammasomes, whereas microbiota-targeted interventions reduce inflammation and support cognitive function. Despite these promising findings, inconsistencies in study methodologies and microbiota analyses limit comparability and clinical translation. This review offers a unique synthesis of studies specifically linking gut microbiota alterations to microglial states, neuroinflammatory signatures, and cognitive outcomes across diverse experimental models. It highlights the therapeutic potential of microbiota-based strategies for modulating microglial function and mitigating neuroinflammatory diseases.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624831","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":"Preface to the Special Issue “History, Biology and Pathobiology of Prions: A Field of Renewed Hopes”","authors":"Tiago F. Outeiro,&nbsp;Tuane C. R. G. Vieira","doi":"10.1111/jnc.70156","DOIUrl":"https://doi.org/10.1111/jnc.70156","url":null,"abstract":"<p>Research in the field of prion diseases has not only shed light on the mechanisms underlying transmissible spongiform encephalopathies (TSEs) but has also influenced the broader understanding of protein misfolding disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and other tauopathies and synucleinopathies. Although prion diseases are rare and invariably fatal, they have provided an invaluable conceptual framework for the study of age-associated neurodegenerative disorders. On the occasion of the “Prion 2023” meeting in Faro, Portugal, which brought together leading experts in prion biology and neurodegeneration to discuss emerging data and evolving concepts, we put together a special issue on the topic to discuss new structural insights, diagnostic technologies, and the increasing recognition of prion-like mechanisms in a wide range of proteinopathies. This Special Issue features six comprehensive review articles that highlight key advances and ongoing challenges in the study of prions and related disorders.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615362","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":"S100a9 Aggravates Ischemia Brain Injury via Pyroptosis Pathway: A Potential Prognostic Biomarker and Therapeutic Target for Ischemic Stroke","authors":"Wenchao Fu,&nbsp;Rui Wang,&nbsp;Yongmei Xu,&nbsp;Lijuan Zhang,&nbsp;Dan Liu,&nbsp;Tao Shen,&nbsp;Yinfei Song,&nbsp;Jingbo Li,&nbsp;Xianzhang Zeng","doi":"10.1111/jnc.70159","DOIUrl":"https://doi.org/10.1111/jnc.70159","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemic stroke, a leading cause of global morbidity and disability, involves incompletely elucidated pathophysiological mechanisms. Emerging evidence highlights pyroptosis—an inflammatory programmed cell death pathway—as a critical contributor to ischemic brain injury progression. The pro-inflammatory mediator S100a9 may exacerbate neuronal damage through pyroptosis regulation, prompting this investigation into its role in post-stroke outcomes and underlying mechanisms. We employed a multi-modal approach integrating public omics datasets, clinical cohorts, murine middle cerebral artery occlusion (MCAO) models, and cellular oxygen–glucose deprivation/reperfusion (OGD/R) systems to delineate expression patterns of S100a9 and pyroptosis-associated biomarkers. Pharmacological targeting of S100a9 using Paquinimod and siRNA-mediated knockdown further defined its functional regulation of pyroptotic cascades. Results demonstrate that S100a9 amplifies neuroinflammatory responses and microglia-specific pyroptosis, correlating with worsened infarct volumes and poor 30-day modified Rankin Scale scores. Targeted S100a9 inhibition attenuated brain injury and neuroinflammation, highlighting its potential as a therapeutic target for stroke intervention.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615365","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":"Oxidative Activity of Copper Ions in Ternary Systems With N-Truncated Amyloid Beta Peptides and Low Molecular Weight Substances","authors":"Dobromiła Sudzik,&nbsp;Wojciech Bal,&nbsp;Nina E. Wezynfeld","doi":"10.1111/jnc.70145","DOIUrl":"https://doi.org/10.1111/jnc.70145","url":null,"abstract":"<div>\u0000 \u0000 <p>Oxidative stress is one of the most characteristic features of Alzheimer's disease. Previous studies revealed that copper complexes of amyloid beta (Aβ) peptides, mainly the Aβ_1-x form, could effectively catalyze the production of reactive oxygen species (ROS), causing the oxidation of physiological compounds. The Cu(II) binding to N-truncated Aβ forms containing His-2 and His-3 motifs produced less oxidative damage by arresting the Cu(II) ions in highly stable Cu(II)/Aβ complexes. This could be reversed, however, by interactions with low molecular weight (LMW) substances. In this work, we investigated the influence of biologically relevant LMW: His-1 dipeptide His-Leu, histidine, imidazole, and neurotransmitters histamine, glycine, and glutamate on the ROS-related ascorbate oxidation by Cu(II) complexes of Aβ peptides comprising the His-2 and His-3 motifs, namely Aβ_4-9, Aβ_5-9, and Aβ_12-16. These peptides are putative products of Aβ hydrolysis by protease neprilysin. A significantly higher efficiency in the ascorbate oxidation was observed for the ternary Cu(II)/Aβ/LMW systems with His-Leu and histidine compared to the binary Cu(II)/Aβ complexes. The effect was more pronounced for the systems with Aβ_4-9 (the His-3 motif only) than those with Aβ_5-9 and Aβ_12-16 (containing the His-2 motif), which is likely connected with a faster Cu(II) trapping by the His-2 peptides compared to the His-3 peptides. The obtained results raise further questions regarding the copper redox activity in Alzheimer's disease.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615363","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":"Label-Free Proteomic Profiling of the dvls2 (CL2006) Caenorhabditis elegans Alzheimer's Disease (AD) Model Reveals Conserved Molecular Signatures Shared With the Human AD Brain","authors":"Iverson Conrado Bezerra,&nbsp;Emily Raphaely Souza dos Santos,&nbsp;Katarine G. Aurista do Nascimento,&nbsp;Artur José da Silva,&nbsp;Josivan Barbosa de Farias,&nbsp;Maria Luiza de Lima Vitorino,&nbsp;Roberto Afonso da Silva,&nbsp;José Luiz de Lima Filho,&nbsp;Priscila Gubert","doi":"10.1111/jnc.70152","DOIUrl":"https://doi.org/10.1111/jnc.70152","url":null,"abstract":"<p>Alzheimer's disease (AD) is the most common form of dementia, posing significant challenges to cognitive, emotional, social, and financial well-being. The biochemical and molecular pathways associated with AD are complex, making it difficult to study and simulate in patients or through in vitro research. Thus, animal models play a crucial role in investigating the development and progression of AD. One widely used model in neuroscience studies is the free-living nematode <i>Caenorhabditis elegans</i> (<i>C. elegans</i>). The development of transgenic animals has allowed for the construction of the <i>dvls2</i> (CL2006) <i>C. elegans</i> strain, which constitutively expresses the amyloid beta (Aβ) peptide. This study conducted a proteomic analysis on the <i>dvls2</i> (CL2006) strain. Also, a cross-species comparative analysis was performed using microarray data from AD patients to identify genes with ontology in the <i>dvls2</i> (CL2006). A total of 543 proteins were found to be differentially regulated in the <i>dvls2</i> (CL2006) strain. Furthermore, in the analysis of the human datasets, 397 upregulated and 767 downregulated genes were identified. The differentially expressed genes (DEGs) were analyzed in Ortholist to identify their orthologs in <i>C. elegans</i>. Then, the orthologous genes in the <i>dvls2</i> (CL2006) model were compared to the proteomic data, resulting in the identification of 29 upregulated and 24 downregulated proteins (DEPs). Functional enrichment analysis of DEPs revealed terms related to pyruvate, glucose, and glutamate metabolism, in addition to binding activities to unfolded proteins and ligases, highlighting the upregulation of chaperone and ubiquitination-associated proteins. Protein–protein network (PPI) was performed for the human DEGs and DEPs of <i>dvls2</i> (CL2006). Topological analyses of the networks were performed, revealing the following <i>C. elegans hub</i> proteins: EEF-2, ALH-13, ENOL-1, RPL-2, TPI-1, CTS-1, RPL-9, RPL-23, CCT-1, and RPS-8. eEF-2 was identified as a key regulator of the human AD PPI and <i>dvls2</i> (CL2006). Modules were analyzed in the networks, and the presence of key regulators was identified. This study provides the first proteomic characterization of the AD model <i>dvls2</i> (CL2006) and a cross-species comparative analysis with data from AD individuals, supporting the use of <i>dvls2</i> (CL2006) in AD studies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615364","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":"Astrocytes Contribute to Motor Neuron Degeneration in ALS via the TRAIL-DR5 Signaling Pathway","authors":"Kangqin Yang,&nbsp;Yang Liu,&nbsp;Wenhua Deng,&nbsp;Zhenxiang Gong,&nbsp;Lifang Huang,&nbsp;Zehui Li,&nbsp;Min Zhang","doi":"10.1111/jnc.70146","DOIUrl":"https://doi.org/10.1111/jnc.70146","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons. The mechanisms underlying the selective degeneration of motor neurons in ALS remain poorly understood, underscoring the need for further investigation into the factors driving this process. In this study, we utilized ALS mouse models and an in vitro NSC34 motor neuron cell line expressing the SOD1^G93A mutation to identify a novel pathogenic mechanism wherein astrocyte-secreted Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to Death Receptor 5 (DR5)on motor neurons, leading to caspase-8 activation and subsequent neuronal death. Blocking DR5 with neutralizing antibodies significantly attenuated TRAIL-induced motor neuron death. These findings provide the first evidence that TRAIL may serve as a potential therapeutic target in ALS, offering new insights into the mechanisms of motor neuron degeneration in this disease.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598539","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":"Self-Report Alzheimer's Disease Statuses in UK Biobank Distort Downstream Analyses","authors":"Shuyuan Hu,&nbsp;Ping Zhu,&nbsp;Shan Gao,&nbsp;Shiyang Wu,&nbsp;Yijie He,&nbsp;Fengzhen Liu,&nbsp;Kun Wang,&nbsp;Guiyou Liu","doi":"10.1111/jnc.70151","DOIUrl":"https://doi.org/10.1111/jnc.70151","url":null,"abstract":"<div>\u0000 \u0000 <p>Genetic studies have identified Alzheimer's disease (AD)-linked variants through genome-wide association studies (GWAS) and proxy-based GWAS (GWAX), yet inconsistent causal inferences still persist. Here, we systematically evaluated how self-reported AD diagnoses in the UK Biobank (UKB) distort Mendelian randomization (MR) analyses. Using seven AD datasets (four GWAS and three GWAX, including IGAP, <i>N</i> = 63 926; FinnGen R10, <i>N</i> = 191 061; UKB G30, <i>N</i> = 420 531; UKB2024, <i>N</i> = 434 286, and GWAX2017, <i>N</i> = 74 366; GWAX2018, <i>N</i> = 548 955; GWAX2021, <i>N</i> = 408 691) and six education subtypes (including years of schooling, <i>N</i> = 1 131 881; hardest math class completed, <i>N</i> = 430 445; self-reported math ability, <i>N</i> = 564 698; college completion, <i>N</i> = 280 007; cognition test performance, <i>N</i> = 257 841; and non-cognitive skills, <i>N</i> = 257 841). We also assessed the heterogeneity and pleiotropy across these datasets. We found opposing causal directions between GWAS and GWAX cohorts. In GWAS datasets, genetic variations related to education were causally linked to a lower risk of AD (OR &lt; 1, <i>p</i> &lt; 0.05), with years of schooling showing the strongest protective effects (OR = 0.71 in IGAP, <i>p</i> &lt; 0.05). Conversely, UKB-based GWAX analyses paradoxically linked education-related traits to increased AD risk (OR &gt; 1, <i>p</i> &lt; 0.05), directly conflicting with the protective associations in clinical AD GWAS results. Genetic heterogeneity was observed in both AD GWAS and GWAX datasets. Pleiotropy was noted in AD outcomes, but MR estimates remained stable after outlier adjustments. Our findings reveal that self-reported AD statuses in UKB distorted genetic effect estimates, particularly for education subtypes requiring validation. The research urges caution in interpreting MR results from GWAX studies that use self-reported endpoints and highlights the need for rigorous phenotyping in biobank studies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582286","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":"Prenatal Exposure to Vaporized High-Potency Cannabis Affects Hippocampal Synaptic Remodeling and Efficacy, Axonal Excitability, and Memory in Offspring","authors":"Andrea Cairus,&nbsp;Facundo Brizolara,&nbsp;Héctor Kunizawa,&nbsp;Vanina Clouzet,&nbsp;Giuliana Gonzalez,&nbsp;Marcela Alsina-Llanes,&nbsp;Lucía Dellepiane,&nbsp;Santiago Fernández,&nbsp;Carlos García-Carnelli,&nbsp;Eleuterio Umpierrez,&nbsp;Michel Borde,&nbsp;José Pedro Prieto,&nbsp;Nathalia Vitureira","doi":"10.1111/jnc.70153","DOIUrl":"https://doi.org/10.1111/jnc.70153","url":null,"abstract":"<div>\u0000 \u0000 <p>Cannabis use during pregnancy has recently become an important concern due to its increasing trend and association with neurodevelopmental alterations of exposed children. Although inhalation is the primary route of cannabis consumption in humans, few studies replicated this route in preclinical models of prenatal exposure. This study aimed to analyze the effects of chronic prenatal exposure to vaporized cannabis (PEVC) on hippocampal neurodevelopment, functionality, and learning and memory processes. Using a commercially available high-potency cannabis strain (THC 14.7%), pregnant rats were exposed to cannabis vapor from gestational day 8 to 21. A combination of primary hippocampal cultures, electrophysiological studies in slices, and behavioral tests was employed to assess the impact of PEVC. We found that PEVC induced presynaptic remodeling of hippocampal neurons in offspring under both basal and activity-dependent conditions by increasing synaptic vGlut1 abundance and the total recycling pool of synaptic vesicles. Chronic PEVC also induced a downregulation of CB1R at glutamatergic and GABAergic synapses. Additionally, an increase in axonal recruitment and synaptic efficacy was observed at hippocampal CA1 synapses of juvenile offspring. Moreover, long-lasting cognitive impairments were identified during adolescence, including deficits in spatial memory in male and female offspring. In summary, these findings demonstrate that exposure to high-potency cannabis vapor during pregnancy leads to significant changes in synaptic remodeling and efficacy, axonal recruitment, and long-term cognitive consequences in offspring.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582290","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}