Journal of Neurochemistry最新文献

{"title":"Hippocampal-Specific Insulin Resistance Elicits Synaptic Effects on Glutamate Neurotransmission","authors":"Jennifer M. Erichsen,&nbsp;Jennifer L. Woodruff,&nbsp;Claudia A. Grillo,&nbsp;Gerardo G. Piroli,&nbsp;Jim R. Fadel,&nbsp;Lawrence P. Reagan","doi":"10.1111/jnc.70083","DOIUrl":"https://doi.org/10.1111/jnc.70083","url":null,"abstract":"<p>Impaired insulin signaling in brain regions such as the hippocampus is thought to contribute to the cognitive deficits associated with conditions such as mild cognitive impairment and Alzheimer's disease. We have previously demonstrated a number of adverse effects in rats with hippocampal-specific insulin resistance, including hippocampal structural defects, impairments in hippocampal-dependent learning and memory, neuroplasticity deficits, behavioral despair, and anxiety-like behaviors. Additionally, we showed that hippocampal-specific insulin resistance decreased the serine phosphorylation of GluA1 and expression of GluN2B. These effects on postsynaptic glutamate receptors were particularly fascinating, due to the proposed theory of the glutamatergic system as a facilitator of hippocampal synaptic transmission. However, the synaptic effects of hippocampal-specific insulin resistance with regard to glutamate neurotransmission had yet to be elucidated. To address this question, we examined hippocampal glutamate neurochemistry and expression of glutamatergic synaptic proteins in rats with hippocampal-specific insulin resistance. We also examined the ability of intranasal insulin to impact glutamatergic synapses. We found decreased synaptic concentrations of glutamate in the hippocampus, likely a result of reduced hippocampal vGluT2 expression. Additionally, hippocampal glutamate efflux was significantly increased in rats with hippocampal-specific insulin resistance in response to a high (12 U), but not a low (0.072 U), dose of intranasal insulin. Our findings indicate that hippocampal-specific insulin resistance elicits synaptic plasticity deficits in glutamatergic synapses, which may be overcome by intranasal insulin administration.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190942","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":"Altered Vesicular Acetylcholine Transporter Expression Regulates Acetylcholine Abundance in the Brain of Drosophila melanogaster","authors":"Rohina A. Nemat,&nbsp;Timothy Chaya,&nbsp;Angeline-Claudia Atheby,&nbsp;Hakeem O. Lawal","doi":"10.1111/jnc.70109","DOIUrl":"https://doi.org/10.1111/jnc.70109","url":null,"abstract":"<p>The neurotransmitter acetylcholine (ACh) plays a central role in the regulation of vital neurological processes like cognition. As a result, increases or decreases in neuronal cholinergic signaling lead to an impairment in learning and memory. Although much about how acetylcholine is regulated is known, the mechanism through which alterations in cholinergic signaling affect changes in ACh-linked behavior is not fully understood. Importantly, the nature of the relationship between vesicular acetylcholine packaging and its release at the synaptic cleft is also unclear. We are interested in using the vesicular acetylcholine transporter (VAChT), which mediates the packaging and transport of acetylcholine (ACh) for exocytotic release, to elucidate the ways in which ACh loading alters its release and metabolism. We used both an overexpression of VAChT and two <i>Vacht</i> mutant lines, <i>Vacht</i>^<i>2</i> and <i>Vacht</i>^<i>8</i>, to increase or decrease the gene's expression respectively. Taking a combined immunohistochemical and biochemical approach, we measured the expression of ACh in VAChT overexpressors, and followed up those studies with an assay for ACh levels as a means of quantifying ACh storage and those of choline, its degradation product. We report that consistent with its well-known role in mediating ACh release, the VAChT overexpression line has elevated total head ACh levels in females but not males while <i>Vacht</i> mutants show strong reductions. By contrast, choline levels are elevated in VAChT overexpressors but unchanged in <i>Vacht</i> mutants. These findings are supported by immunolocalization studies in the fly brain in which the VAChT overexpressors show both elevated ACh in and around ACh neurons and an increased localization to synaptic release sites. When we analyzed the immunostaining studies by sex, we found that in contrast to the neurochemical studies, both males and females had elevated ACh levels, while the two <i>Vacht</i> mutants had reductions in that neurotransmitter's levels. By our estimation, these data represent the first time that acetylcholine has been measured directly in VAChT overexpression and <i>Vacht</i> mutants in <i>Drosophila</i> and demonstrate a consistency with findings from mammalian 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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190939","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":"Neural Metabolic Networks: Key Elements of Healthy Brain Function","authors":"Nimrod Madrer,&nbsp;Nirma D. Perera,&nbsp;Nonthué A. Uccelli,&nbsp;Alice Abbondanza,&nbsp;Jens V. Andersen,&nbsp;Emma Veronica Carsana,&nbsp;Matthew D. Demmings,&nbsp;Regina F. Fernandez,&nbsp;Matheus Garcia de Fragas,&nbsp;Ismail Gbadamosi,&nbsp;Divita Kulshrestha,&nbsp;Ricardo A. S. Lima-Filho,&nbsp;Oana C. Marian,&nbsp;Kia H. Markussen,&nbsp;Andrew J. McGovern,&nbsp;Elliott S. Neal,&nbsp;Sukanya Sarkar,&nbsp;Eva Šimončičová,&nbsp;Jazmín Soto-Verdugo,&nbsp;Sozerko Yandiev,&nbsp;Ignacio Fernández-Moncada","doi":"10.1111/jnc.70084","DOIUrl":"https://doi.org/10.1111/jnc.70084","url":null,"abstract":"<p>Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and <i>Journal of Neurochemistry</i> (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190943","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 Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus","authors":"Del Angel,&nbsp;Atsuhiro Tsutiya,&nbsp;Hussam Hayani,&nbsp;Deniz Madencioglu,&nbsp;Emre Kul,&nbsp;Gürsel Caliskan,&nbsp;Yunus Emre Demiray,&nbsp;Alexander Dityatev,&nbsp;Oliver Stork","doi":"10.1111/jnc.70094","DOIUrl":"https://doi.org/10.1111/jnc.70094","url":null,"abstract":"<p>Nuclear Dbf2-related (NDR) kinases are core components of the Hippo pathway, which controls neuronal polarity and neurite growth in the central nervous system (CNS). NDR2 is the principal NDR kinase in the mouse CNS, where it has been shown to regulate integrin-dependent dendritic branching as well as growth and plasticity in hippocampal mossy fibers. Given the well-established involvement of integrins in plasticity, we hypothesized that NDR2 might regulate synapse formation and plasticity through integrin-mediated mechanisms. In this study, using constitutive NDR2 null mutant mice, we demonstrate that Ndr2 deficiency leads to a reduction of T788/789 phosphorylated β1 integrin expression at synaptic sites both in the hippocampal area CA1 and in primary hippocampal neurons in vitro. This reduction is associated with decreased synaptic density in both conditions and accompanied by reduced long-term potentiation in the synapses between Schaffer collaterals/commissural fibers and CA1 pyramidal cells, which could be restored by activation of integrins with an arginine-glycine-aspartate-containing peptide, as well as with mild spatial memory deficits. Together, our results suggest that NDR2 is involved in integrin-dependent synapse formation and plasticity in the mouse hippocampus.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171673","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":"Prenatal Exposure to Lipopolysaccharide or Valproate Leads to Abnormal Accumulation of the NMDA Receptor Agonist D-Aspartate in the Adolescent Rat Brain","authors":"Anna Di Maio,&nbsp;Isar Yahyavi,&nbsp;Valeria Buzzelli,&nbsp;Zoraide Motta,&nbsp;Fabrizio Ascone,&nbsp;Lorenza Putignani,&nbsp;Alessandro Usiello,&nbsp;Loredano Pollegioni,&nbsp;Viviana Trezza,&nbsp;Francesco Errico","doi":"10.1111/jnc.70095","DOIUrl":"https://doi.org/10.1111/jnc.70095","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a neurodevelopmental psychiatric condition linked to glutamatergic neurotransmission disruption. Although endogenous D-serine and D-aspartate modulate glutamatergic N-methyl D-aspartate receptor (NMDAR) activity, their involvement in ASD remains elusive. We measured the levels of D-aspartate, D-serine, and other key neuroactive amino acids, and their direct precursors in brain regions, plasma, and feces of environmental ASD rat models prenatally exposed to lipopolysaccharide or valproate, both during adolescence and early adulthood, as well as in a genetic ASD model, the <i>Fmr1-^Δexon8</i> rat. No significant changes were found in plasma and feces. Conversely, we observed a prominent accumulation of D-aspartate in several brain regions of lipopolysaccharide- and valproate-exposed rats, selectively during adolescence, while D-serine level variations were more limited. No significant amino acid changes were observed in the <i>Fmr1-^Δexon8</i> rat brain. We also assayed the activity of the main enzymes involved in cerebral D-serine and D-aspartate metabolism, suggesting that their regulation extends beyond their metabolic enzymes. These findings highlight that prenatal environmental stressors disrupt D-amino acid levels selectively in ASD rat brains, emphasizing the role of early NMDAR dysfunction in ASD-related phenotypes.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171699","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 ‘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}