Journal of Neurochemistry最新文献

{"title":"Correction to ‘EXPRESSION OF CONCERN: Combined Pharmacological, Mutational and Cell Biology Approaches Indicate That p53-Dependent Caspase 3 Activation Triggered by Cellular Prion Is Dependent on Its Endocytosis’","authors":"","doi":"10.1111/jnc.70096","DOIUrl":"https://doi.org/10.1111/jnc.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>(2025) EXPRESSION OF CONCERN: Combined Pharmacological, Mutational and Cell Biology Approaches Indicate That p53-Dependent Caspase 3 Activation Triggered by Cellular Prion Is Dependent on Its Endocytosis. <i>J Neurochem</i>, 169: e70074. https://doi.org/10.1111/jnc.70074</p>\u0000 <p>In the above Expression of Concern, there was an error in the text.</p>\u0000 <p>The text, ‘Author F. Checler disagrees with the Retraction’ should have read ‘Author F. Checler disagrees with the Expression of Concern’.</p>\u0000 <p>We apologize for this error.</p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140358","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":"A Computational Approach to Identify Novel Protein Targets Uncovers New Potential Mechanisms of Action of Mirtazapine S(+) and R(−) Enantiomers in Rett Syndrome","authors":"Ottavia Maria Roggero,&nbsp;Nicolò Gualandi,&nbsp;Viviana Ciraci,&nbsp;Vittoria Berutto,&nbsp;Emanuele Carosati,&nbsp;Enrico Tongiorgi","doi":"10.1111/jnc.70093","DOIUrl":"https://doi.org/10.1111/jnc.70093","url":null,"abstract":"<p>Rett syndrome (RTT) is a progressive neurodevelopmental disorder that affects approximately 1:10000 newborn girls and is primarily caused by mutations in the X-linked gene <i>MECP2</i>. Due to reduced brain monoamine levels in RTT, antidepressants have been explored as potential therapies. In previous studies, we demonstrated that the antidepressant mirtazapine (MTZ) alleviates symptoms in <i>Mecp2</i>-mutant mice and RTT adult patients. However, the mechanism of action of MTZ, a racemic mixture that binds to multiple receptors, remains unclear. This study introduces a computational approach to screen the “human pocketome,” comprising over 25 K ligand-bound pockets derived from more than 210 K human protein structures available in the RCSB Protein Data Bank, aiming to identify binding pockets with high affinity for each MTZ enantiomer. Novelty concerns the approach to compare the two enantiomers of MTZ to other drugs experimentally determined as inactive for RTT. This approach introduces a new metric, the ZZscore, which ranks tested proteins and pockets based on their degree of interaction with the tested drugs. This enables the identification of potential drug-protein interactions relevant to the disease and/or phenotypic traits under study. Initial relaxed settings and thresholds parameters suggested over 30 potential targets, among which the RASH/SOS1 complex, but in vitro experiments on cultured hippocampal neurons from <i>Mecp2</i>-KO mice excluded any MTZ effect on it. Thus, we refined the procedure with more stringent parameters and identified 16 protein targets for <i>S</i>(+)MTZ and 14 for <i>R</i>(−)MTZ, with 5 common targets. Pathway enrichment analysis revealed 25 pathways for <i>S</i>(+)MTZ and 24 for <i>R</i>(−)MTZ, with 11 common pathways, many related to MeCP2 functions disrupted in RTT, such as epigenetic chromatin regulation, intracellular signaling, energy metabolism, cholesterol and lipid metabolism, and catecholamine biosynthesis. Overall, the presented computational modeling strategy for target identification allowed us to hypothesize new mechanisms of action for the two MTZ enantiomers.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135597","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":"Association of Peak Width of Skeletonized Mean Diffusivity With Neurofilament Light Chain in Non-Dementia Adults","authors":"Rui-Ping Cui,&nbsp;He-Ying Hu,&nbsp;Shuang-Ling Han,&nbsp;Shu-Yu Liang,&nbsp;Min Liu,&nbsp;Pei-Yang Gao,&nbsp;Yan-Ming Chen,&nbsp;Yu-Dong Wang,&nbsp;Fan Guo,&nbsp;Rong-ji Xue,&nbsp;Meng-Shan Tan,&nbsp;Hao Hu,&nbsp;Lan Tan","doi":"10.1111/jnc.70076","DOIUrl":"https://doi.org/10.1111/jnc.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>Peak width of skeletonized mean diffusivity (PSMD) effectively reflects the mean diffusivity distribution across the white matter and is considered a novel biomarker for cerebral small vessel disease (CSVD). Neurofilament light chain (NFL) is observed to be released in neurodegenerative diseases with large myelinated axonal degeneration. In our research, we explored the relationship of PSMD with NFL levels in non-dementia adults. In the Alzheimer's Disease Neuroimaging Initiative, after adjusting for potential confounders, we used linear regression models to study the relationship of PSMD with plasma NFL levels in the total population and different white matter brain regions. Additionally, we analyzed the relationships in subgroups. Furthermore, we used a linear mixed effects model to assess the long-term effect of baseline PSMD on longitudinal changes in plasma NFL levels. The results showed that PSMD was correlated with elevated plasma NFL levels in the total population, with significant associations observed in late-life, <i>APOE</i>4 non-carriers, and A− (amyloid-negative) subgroups. Further analysis of different white matter brain regions revealed a correlation in the body of the corpus callosum, superior corona radiata, posterior thalamic radiation, sagittal stratum, fornix/stria terminalis, and superior fronto-occipital fasciculus. Moreover, individuals with higher PSMD demonstrated a faster increase in plasma NFL levels in the total population, which was significant in the late-life and A− subgroups. This study demonstrated that PSMD was associated with plasma NFL, suggesting that CSVD was related to neurodegenerative disorders, particularly in the body of the corpus callosum, superior corona radiata, posterior thalamic radiation, sagittal stratum, fornix/stria terminalis, and superior fronto-occipital fasciculus. At the same time, PSMD would exacerbate the damage to plasma NFL levels. These findings support the idea that plasma NFL may be a promising biomarker for CSVD.\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 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140374","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":"Molecular Underpinnings of Memory Persistence and Forgetting","authors":"Juliana F. Dalto,&nbsp;Jorge H. Medina,&nbsp;Verónica Pastor","doi":"10.1111/jnc.70089","DOIUrl":"https://doi.org/10.1111/jnc.70089","url":null,"abstract":"<p>The fate of memories depends mainly on external and internal factors affecting cellular and systems consolidation on the one hand and the decay or weakening of the memory trace on the other hand. Over the past 40 years, research has focused on the mechanisms of memory consolidation, retrieval, and its consequences: extinction and reconsolidation. In contrast, much less is known about the molecular mechanisms required for the maintenance of memory storage and forgetting. These opposing forces are both activity- and time-dependent. Here, we summarize the molecular signatures and inherent mechanisms involved in memory persistence and active forgetting, highlighting recent findings on the role of dopamine neurotransmission, intracellular signaling cascades, and actin cytoskeleton dynamics in these processes.\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 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125957","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 Effects of Exercise-Associated Factors on Hippocampal Progenitor Cell Dynamics Are Mediated by Cannabinoid Type 2 Receptors","authors":"R. S. Rodrigues,&nbsp;J. B. Moreira,&nbsp;P. Dias,&nbsp;A. M. Sebastião,&nbsp;S. Xapelli","doi":"10.1111/jnc.70091","DOIUrl":"https://doi.org/10.1111/jnc.70091","url":null,"abstract":"<div>\u0000 \u0000 <p>Neural stem/progenitor cells (NSPCs) operate in specialized niches of the adult mammalian brain, where their proliferative and differentiative potential is modulated by a myriad of factors. Emerging evidence sheds light on the interaction between cannabinoids and neurotrophic factors underlying a major regulatory force of NSPC dynamics. Previous data show that cannabinoid type 2 receptors (CB2Rs) tightly regulate the actions of brain-derived neurotrophic factor (BDNF), a neurotrophic factor highly upregulated during physical exercise. However, further research into the effects of exercise-associated neurotrophic factors in the regulation of NSPCs is still necessary. Therefore, we aimed at exploring the effects of exercise-associated factors in postnatal hippocampal neurogenesis and how CB2Rs regulate this process. By using dentate gyrus-derived neurospheres and treating them with a combination of exercise-associated factors, as an in vitro proxy for exercise, we found that these factors significantly promoted cell proliferation, an action partially reduced when CB2Rs were blocked. Moreover, CB2Rs were shown to be required for the actions of this exercise-mimicking cocktail in early neuronal commitment and differentiation. However, late neuronal differentiation promoted by exercise-associated factors remained unaltered in the presence of CB2R ligands. Together, these data suggest that CB2R actions are preponderant in early stages of hippocampal neurogenesis promoted by exercise. Astroglial late differentiation was also accelerated by a combination of exercise-associated factors, an effect prevented by CB2R blockage. This work provides a deeper understanding of the mechanisms underlying the actions of cannabinoids and exercise on NSPC regulation, highlighting the role of CB2R in modulating exercise-induced hippocampal neurogenesis.\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 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117951","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":"Tubulin and GTP Are Crucial Elements for Postsynaptic Density Construction and Aggregation","authors":"Tatsuo Suzuki,&nbsp;Toshihiro Fujii,&nbsp;Kiyokazu Kametani,&nbsp;Weidong Li,&nbsp;Katsuhiko Tabuchi","doi":"10.1111/jnc.70085","DOIUrl":"https://doi.org/10.1111/jnc.70085","url":null,"abstract":"<p>In our previous experiments on the postsynaptic density lattice (PSDL), which is thought to serve as the backbone structure for the PSD, we suggested that tubulin plays a fundamental role in the PSD structure at excitatory synapses. In this study, we further reveal an unrecognized characteristic of tubulin within the PSD. First, using electron microscopy, we identified an interaction between postsynaptic structures (PSDL and PSD) and polymerizing microtubules, which led to the binding of polymerizing microtubules to PSDL and PSD. In turn, this interaction induced changes in the microtubule morphology. These results support earlier findings suggesting that microtubules transiently intruding into the spine head can associate with PSDs, inducing structural changes in the PSD. Next, we observed that the structural integrity of both PSD and PSDL was compromised upon exposure to GTP and microtubule-affecting reagents. These findings reinforce the idea that tubulin is a crucial building block of the PSD architecture. Moreover, we found that PSD aggregation was enhanced following interactions with polymerizing tubulin and was disintegrated upon treatment with GTP and microtubule-affecting reagents. These results indicate that microtubules also play a key role in PSD aggregation in vitro. Collectively, our study highlights the involvement of tubulin in the construction, function (specifically its interaction with polymerizing microtubules), and aggregation of the PSD, which may impact both physiological and pathological conditions. Furthermore, our in vitro findings suggest that GTP can either destroy or induce the enlargement and reorganization of PSD structures, depending on its interaction with growing microtubules.\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 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100498","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":"Astrocyte Dysfunctions in Obsessive Compulsive Disorder: Rethinking Neurobiology and Therapeutic Targets","authors":"Laurine Gonzalez,&nbsp;Paola Bezzi","doi":"10.1111/jnc.70092","DOIUrl":"https://doi.org/10.1111/jnc.70092","url":null,"abstract":"<p>Obsessive-compulsive disorder (OCD) has long been conceptualized as a neuron-centric disorder of cortico-striato-thalamo-cortical (CSTC) circuit dysregulation. However, a growing body of evidence is now reframing this narrative, placing astrocytes—once relegated to passive support roles—at the center of OCD pathophysiology. Astrocytes are critical regulators of glutamate and GABA homeostasis, calcium signaling, and synaptic plasticity, all of which are disrupted in OCD. Recent high-resolution molecular and proteomic studies reveal that specific astrocyte subpopulations, including <i>Crym</i>-positive astrocytes, directly shape excitatory/inhibitory balance and control perseverative behaviors by modulating presynaptic inputs from the orbitofrontal cortex. Disruptions in astrocytic neurotransmitter clearance and dopamine metabolism amplify CSTC circuit hyperactivity and reinforce compulsions. This review reframes OCD as a disorder of neuro-glial dysfunctions, proposing that targeting astrocytic signaling, metabolism, and structural plasticity may unlock transformative therapeutic strategies. By integrating human and animal data, we advocate for a glial-centric model of OCD that not only enhances mechanistic understanding but also opens new frontiers for precision treatment.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108877","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":"Presymptomatic Biological, Structural, and Functional Diagnostic Biomarkers of Autism Spectrum Disorder","authors":"Bonnie M. Wang,&nbsp;Zoe Mills,&nbsp;Hannah F. Jones,&nbsp;Johanna M. Montgomery,&nbsp;Kevin Y. Lee","doi":"10.1111/jnc.70088","DOIUrl":"https://doi.org/10.1111/jnc.70088","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a common neurodevelopmental disorder clinically diagnosed by persistent deficits in three areas of social communication and interaction, plus at least two of four types of restricted repetitive behaviors. ASD has been shown to be caused by genetic predisposition and environmental factors; however, the heterogeneity of ASD complicates its diagnosis and treatment. Early behavioral interventions have shown significant benefits, emphasizing the urgent need for reliable diagnostic biomarkers to enhance long-term outcomes. Here we provide a systematic review that outlines current findings on genetic and neurological biomarkers for presymptomatic ASD diagnoses, assessed prior to the observation of behavioral manifestations. Specifically, we offer insights into the mechanisms of presymptomatic neurological, biological, structural, and functional markers for ASD, compare outcomes across studies, and critically assess their limitations and implications. Recent findings highlight genotype-guided therapeutic strategies in animal models, such as dietary zinc supplementation for reversing ASD-associated behaviors by synaptic deficits. However, the differential efficacy based on underlying genotypes, along with challenges in identifying reliable genomic biomarkers prior to symptom onset, indicates the need for further research. Notably, recent advancements in imaging technologies like magnetic resonance imaging, electroencephalography, and pupillometry have shown promising markers in neonates, and at 3 and 9 months old, respectively. Newer developments in magnetoencephalography hardware can facilitate the much-needed infant ASD studies. It is important to note that many of these biomarker findings are preliminary, and further validation for clinical use is required. Continued research is needed to advance the practicality, reliability, and acceptability of these biomarkers to improve ASD diagnosis and treatment strategies.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091307","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":"Tomatidine Ameliorates Diabetes-Induced Cognitive Impairment and Tau Hyperphosphorylation Through the AMPK-TFEB Pathway","authors":"Wei-Gang Zhang,&nbsp;Jian Ding,&nbsp;Lei Wang,&nbsp;Cheng-Jun Wu,&nbsp;Jia-Yue Mao,&nbsp;Kun Ding,&nbsp;Cui Zhang,&nbsp;Ze-Bo Hu,&nbsp;Shu Li,&nbsp;Lin Wang","doi":"10.1111/jnc.70087","DOIUrl":"https://doi.org/10.1111/jnc.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes is associated with an increased risk of cognitive impairment. Autophagy–lysosomal dysfunction is a key feature of diabetes that contributes to dementia. Transcription factor EB (TFEB) is a master regulator of the autophagy–lysosomal function. Although the TFEB level and activity are known to be significantly decreased in transgenic mouse models of Alzheimer's disease, the role of TFEB in diabetes-associated cognitive decline remains unknown. Tomatidine protects nerve cells through reduced inflammation, oxidative stress, and cell apoptosis, which also increases the TFEB expression. In the present study, we elucidated whether tomatidine activates TFEB and ameliorates diabetes-associated cognitive impairment. The results revealed that tomatidine ameliorated diabetes-induced cognitive impairment and tau protein hyperphosphorylation through TFEB activation. Furthermore, tomatidine activated AMP-activated protein kinase (AMPK). When AMPK was inhibited, the improvement role of tomatidine disappeared. Taken together, tomatidine exerted a partial protective effect on diabetes-associated cognitive impairment by modulating the AMPK–TFEB signaling pathway.\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 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085394","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":"Chronic Vanadium Exposure Promotes Aggregation of Alpha-Synuclein, Tau and Amyloid Beta in Mouse Brain","authors":"O. R. Folarin,&nbsp;F. E. Olopade,&nbsp;T. T. Gilbert,&nbsp;A. D. Ladagu,&nbsp;P. I. Pires dos Santos,&nbsp;O. A. Mustapha,&nbsp;L. Z. Kpasham,&nbsp;J. O. Olopade,&nbsp;T. F. Outeiro","doi":"10.1111/jnc.70082","DOIUrl":"https://doi.org/10.1111/jnc.70082","url":null,"abstract":"<p>The interaction of toxic environmental metals and metalloids with brain proteins and polypeptides can result in pathological aggregations and formation of toxic oligomers, which are key features of many neurodegenerative diseases. Occupational and environmental exposure to vanadium is connected to a neurological syndrome that includes psychiatric symptoms, cognitive decline, and neurodegeneration. In this study, we hypothesized that prolonged vanadium exposure may be a potential risk factor for Alzheimer's and Parkinson's diseases. A total of 72 male BALB/c mice, each 4 weeks' old, were used. Vanadium-treated groups received intraperitoneal injections of 3 mg/kg body weight of vanadium three times a week for 6, 12, or 18 months. The control group received sterile water while the withdrawal group were given vanadium injection for 3 months, followed by withdrawal of the metal, but treatment with sterile water only, and were sacrificed at 3-, 9-, or 15-months post vanadium exposure. Sagittal sections of brain paraffin-embedded tissue were prepared and analyzed using immunofluorescence to study the immunoreactivity and cellular localization of α-synuclein (α-syn), amyloid-β (Aβ), and tau proteins. Our findings revealed pathological aggregation of these proteins in the frontoparietal cortices and the dorsal CA1 and CA3 regions. Double immunolabeling with glial cells and neurons showed neuronal degeneration, functional gliosis, and activation of astrocytes and microglia at sites of α-synuclein immunoreactivity. We observed increased immunoreactivity of phosphorylated nuclei tau both in the parietal cortices and corpus callosum white matter while we observed intraneuronal accumulation of Aβ deposits in the cortex and dorsal hippocampal regions in vanadium treated brains. These cellular changes and proteinopathies, although persisting, were significantly attenuated after vanadium withdrawal. Our findings show that prolonged vanadium exposure promotes abnormal accumulation of neurodegeneration-associated proteins (α-syn, Tau, and Aβ) in the brain, which is further exacerbated by aging in the context of extended exposure to the metal.\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 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074498","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}