Journal of Neurochemistry最新文献

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Single Cell Sequencing Reveals Cellular Heterogeneity in Mouse Dorsal Root Ganglion. 单细胞测序揭示小鼠背根神经节细胞异质性。
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-08-01 DOI: 10.1111/jnc.70180
Yiting Chen, Yuying Wang, Yucong Zhu, Xinyu Zheng, Jing Wang, Xiuyu Nong, Xi Chen, Lingzhi Wang, Ailin Tao, Xueting Liu
{"title":"Single Cell Sequencing Reveals Cellular Heterogeneity in Mouse Dorsal Root Ganglion.","authors":"Yiting Chen, Yuying Wang, Yucong Zhu, Xinyu Zheng, Jing Wang, Xiuyu Nong, Xi Chen, Lingzhi Wang, Ailin Tao, Xueting Liu","doi":"10.1111/jnc.70180","DOIUrl":"https://doi.org/10.1111/jnc.70180","url":null,"abstract":"<p><p>The dorsal root ganglion plays a crucial role in sensory transduction and modulation. Nevertheless, the specific physiological functions of the diverse cell types within the dorsal root ganglion remain poorly understood. Here, three physiologic mouse dorsal root ganglion data (GSE155622) were obtained from the NCBI database, yielding data on a total of 14 902 cells. Based on the genetic profiles, we identified neurons, immune cells, fibroblasts, satellite glial cells, Schwann cells, vascular endothelial cells, and vascular smooth muscle cells. Our results found functional enrichment of each cell subtype utilizing QuSAGE, GO, and KEGG enrichment methodologies, determined the evolutionary trajectories of cell subtypes through pseudo-temporal analysis, and constructed a comprehensive cellular communication network. Furthermore, RNAscope in situ hybridization and ISH-IHC double staining were performed to verify the expression of marker genes and itch-related genes in DRG tissues of C57BL/6 mice with no treatment. In summary, our findings reveal cellular heterogeneity in mouse dorsal root ganglion, which offers novel insights into the physiology of mice.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":"e70180"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794752","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}
引用次数: 0
Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin. 磷酸肌肽和粘菌素依赖的酞菁突触聚类。
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-08-01 DOI: 10.1111/jnc.70169
Nele Burdina, Filip Liebsch, Arthur Macha, Joaquín Lucas Ortuño Gil, Pia Frommelt, Irina Rais, Fabian Basler, Simon Pöpsel, Guenter Schwarz
{"title":"Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin.","authors":"Nele Burdina, Filip Liebsch, Arthur Macha, Joaquín Lucas Ortuño Gil, Pia Frommelt, Irina Rais, Fabian Basler, Simon Pöpsel, Guenter Schwarz","doi":"10.1111/jnc.70169","DOIUrl":"10.1111/jnc.70169","url":null,"abstract":"<p><p>Gephyrin is the main scaffolding protein at inhibitory synapses, clustering glycine and GABA<sub>A</sub> receptors. At specific GABAergic synapses, the nucleotide exchange factor collybistin recruits gephyrin to the postsynaptic membrane via interaction with phosphoinositides. However, the molecular mechanisms underlying the formation, maintenance, and regulation of collybistin-dependent gephyrin clusters remain poorly understood. This study sheds light on the molecular mechanism of gephyrin cluster formation on the basis of gephyrin self-oligomerization induced by collybistin, leading to the formation of a high-molecular weight (> 5 MDa) gephyrin-collybistin complex, which is regulated in two ways: First, plasma-membrane phosphoinositides promote complex formation, demonstrating their critical role in membrane targeting and stabilization of gephyrin-collybistin clusters at postsynaptic sites. Second, gephyrin phosphorylation at Ser325 abolishes complex formation with collybistin, thus impairing collybistin-dependent gephyrin clustering at GABAergic synapses. Collectively, our data demonstrate a molecular mechanism for synaptic clustering of gephyrin, which involves collybistin- and phosphoinositide-dependent formation of high-molecular weight gephyrin oligomers.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":"e70169"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804316","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}
引用次数: 0
The Role of Extracellular Vesicles in Brain-Peripheral Communication Following Ischemic Stroke: Implications for Neural Repair and Regeneration 缺血性卒中后细胞外囊泡在脑外周通讯中的作用:对神经修复和再生的影响
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-31 DOI: 10.1111/jnc.70155
Victória Linden de Rezende, Khiany Mathias, Maiara de Aguiar da Costa, Cinara Ludvig Gonçalves, Tatiana Barichello, Fabricia Petronilho
{"title":"The Role of Extracellular Vesicles in Brain-Peripheral Communication Following Ischemic Stroke: Implications for Neural Repair and Regeneration","authors":"Victória Linden de Rezende,&nbsp;Khiany Mathias,&nbsp;Maiara de Aguiar da Costa,&nbsp;Cinara Ludvig Gonçalves,&nbsp;Tatiana Barichello,&nbsp;Fabricia Petronilho","doi":"10.1111/jnc.70155","DOIUrl":"https://doi.org/10.1111/jnc.70155","url":null,"abstract":"<p>Ischemic stroke (IS) triggers complex neuroinflammatory and regenerative responses that extend beyond the brain. Extracellular vesicles (EVs), released by both central nervous system (CNS) and peripheral cells, have emerged as key mediators of communication between the brain and peripheral organs following IS. EVs are capable of transporting bioactive molecules across theblood-brain barrier (BBB), modulating systemic immune responses, influencing neuroinflammation, and promoting tissue repair. Additionally, peripheral EVs derived from immune cells, adipose tissue, bone, and the gut microbiota can impact brain recovery processes. This narrative review explores the dynamic and bidirectional roles of EVs in brain-periphery communication after stroke, highlighting their potential as diagnostic biomarkers and therapeutic agents. Despite promising preclinical findings, further research is needed to standardize experimental protocols, clarify the mechanisms of EV action, and advance their translation into clinical applications.</p><p>\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 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751503","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}
引用次数: 0
Colony Stimulating Factor-1 (CSF-1) and Interleukin-34 (IL-34) Differentially Alter White Matter and Gray Matter Microglia and Oligodendrocyte Progenitor Cells 集落刺激因子-1 (CSF-1)和白细胞介素-34 (IL-34)改变白质和灰质小胶质细胞和少突胶质细胞祖细胞的差异
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-31 DOI: 10.1111/jnc.70186
Audrée S. Rumberger, Lauryn A. Vassel, Caroline C. Hess, Annabel S. Barnett, Brady J. Johnson, Sayed Hassan, Jonathan P. Godbout, Anzela Niraula
{"title":"Colony Stimulating Factor-1 (CSF-1) and Interleukin-34 (IL-34) Differentially Alter White Matter and Gray Matter Microglia and Oligodendrocyte Progenitor Cells","authors":"Audrée S. Rumberger,&nbsp;Lauryn A. Vassel,&nbsp;Caroline C. Hess,&nbsp;Annabel S. Barnett,&nbsp;Brady J. Johnson,&nbsp;Sayed Hassan,&nbsp;Jonathan P. Godbout,&nbsp;Anzela Niraula","doi":"10.1111/jnc.70186","DOIUrl":"https://doi.org/10.1111/jnc.70186","url":null,"abstract":"<div>\u0000 \u0000 <p>Colony stimulating factor-1 receptor (CSF-1R) signaling is necessary for microglia development and maintenance throughout life. The CSF-1R ligands, CSF-1 and interleukin-34 (IL-34), are indispensable for microglia survival in white matter and gray matter, respectively. While CSF-1 has been studied to a greater extent, the role of IL-34 in microglia function and in the brain overall is much less understood. Here, we examined the region-specific effects of intracerebroventricular (i.c.v.) CSF-1 and IL-34 administration on microglia and oligodendrocyte lineage cells in mice at two timepoints. At 3 days post-intervention, IL-34 increased microglial CD68 levels and the microglia population in the hippocampal CA1 region, whereas CSF-1 increased the microglia population in the corpus callosum. Furthermore, CSF-1, but not IL-34, reduced the oligodendrocyte progenitor cell population in the corpus callosum. These effects were no longer observed at 7 days, revealing the transient nature of the microglial response. Together, these findings demonstrate that in addition to relying on specific signals for survival, microglia respond differently to CSF-1R ligands in a brain microenvironment-dependent manner. These findings highlight the need to better understand microglia in the context of their location, which could provide key insights into the pathogenesis of neuroimmune disorders that predominantly affect gray matter or white matter areas.</p>\u0000 <p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740118","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}
引用次数: 0
Alzheimer's Disease: Treatment Challenges for the Future 阿尔茨海默病:未来的治疗挑战
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-31 DOI: 10.1111/jnc.70176
John Hardy
{"title":"Alzheimer's Disease: Treatment Challenges for the Future","authors":"John Hardy","doi":"10.1111/jnc.70176","DOIUrl":"https://doi.org/10.1111/jnc.70176","url":null,"abstract":"<p>The approvals of the first anti-amyloid antibodies for the treatment of Alzheimer's disease have changed both the clinical and research landscape for the disease. These antibodies, lecanemab and donanemab, mark a turning point for our understanding of the disease pathogenesis and for the treatment of this prevalent disorder. This review discusses what they imply for disease pathogenesis and what is needed to progress from the current imperfect therapies toward safe and better, disease halting therapies. The research over the next period will involve drug development, largely aimed at reducing the side effects of the anti-amyloid therapies, biomarker and genetic research to try and identify patients earlier in the disease process, and neuropathological research in individuals who have received treatment to try and understand the pathological substrates of the continuing clinical decline in the disease.</p><p>\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 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740534","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}
引用次数: 0
Differential Regulation of Proteins Related to the Blood–Brain Barrier in Stress-Resilient and Stress-Susceptible Mice 应激复原和应激易感小鼠血脑屏障相关蛋白的差异调控
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-30 DOI: 10.1111/jnc.70172
Joanna Solich, Agata Faron-Górecka, Magdalena Kolasa, Paulina Pabian, Agata Korlatowicz-Pasieka, Marta Dziedzicka-Wasylewska
{"title":"Differential Regulation of Proteins Related to the Blood–Brain Barrier in Stress-Resilient and Stress-Susceptible Mice","authors":"Joanna Solich,&nbsp;Agata Faron-Górecka,&nbsp;Magdalena Kolasa,&nbsp;Paulina Pabian,&nbsp;Agata Korlatowicz-Pasieka,&nbsp;Marta Dziedzicka-Wasylewska","doi":"10.1111/jnc.70172","DOIUrl":"https://doi.org/10.1111/jnc.70172","url":null,"abstract":"<div>\u0000 \u0000 <p>Stress is considered a primary contributor to mood disorders, such as depression. Therefore, preclinical research encompasses the biochemical and molecular aspects of stress. In the present study, we investigated the effects of restraint stress (RS) on three strains of mice with varying susceptibility to RS: transgenic mice lacking the gene encoding the noradrenergic transporter (NET-KO) and Swiss SWR/J, both displaying a stress-resilient phenotype, and C57Bl/6J (WT), which is stress-susceptible. <i>In silico</i> analysis of a group of microRNAs (miRNAs) differentiating these phenotypes indicated that their target mRNAs encode various proteins that are involved in maintaining the integrity of the blood–brain barrier (BBB). Further analyses using Custom TaqMan Gene Expression Array Cards revealed alterations in these mRNAs in four brain regions of mice subjected to RS. Protein levels were examined with immunohistofluorescence and indicated changes in the levels of two key proteins, claudin-5 (CLDN5) and caveolin-1 (CAV1), and their co-localization with the endothelial cell marker CD31 protein. Additionally, we used fluorescein sodium salt to examine BBB permeability in the mouse strains and found higher permeability in stress-susceptible animals. The most intriguing finding was the differential expression of <i>Cav1</i> mRNA and protein levels in the brain regions of stress-resilient mice compared to the stress-susceptible strain. This suggests that CAV1 may play an important role in the BBB of stress-resilient individuals under stress conditions.</p>\u0000 <p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725478","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}
引用次数: 0
Unveiling the Critical Moments: How Early-Life Seizures Shape Adult Epileptogenesis 揭示关键时刻:生命早期癫痫如何影响成人癫痫发生
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-30 DOI: 10.1111/jnc.70171
Wenjing Wang, Jiajia Ying, Jiannong Wu, Yi Wang, Lin Yang, Zhong Chen
{"title":"Unveiling the Critical Moments: How Early-Life Seizures Shape Adult Epileptogenesis","authors":"Wenjing Wang,&nbsp;Jiajia Ying,&nbsp;Jiannong Wu,&nbsp;Yi Wang,&nbsp;Lin Yang,&nbsp;Zhong Chen","doi":"10.1111/jnc.70171","DOIUrl":"https://doi.org/10.1111/jnc.70171","url":null,"abstract":"<p>Early-life seizure (ELS) represents a condition characterized by ictal events occurring during the early stages of childhood, with particularly high incidence in the neonatal period and infancy. ELS is triggered by a variety of causes, including simply a fever, perinatal asphyxia, brain damage, or genetic abnormalities. Emerging evidence indicates that ELS exerts profound and enduring effects on brain development, predisposing individuals to heightened risks of epilepsy persisting into adulthood. Several shared mechanisms underpin the increased adult epileptogenesis resulting from diverse ELS subtypes, including febrile seizures (FS), chemoconvulsants-induced seizures, and hypoxia-associated seizures. This review systematically examines the long-term consequences on adult epileptogenesis of ELS, focusing on maladaptive plasticity in neuronal networks, reactive gliosis, sustained neuroinflammatory responses, and progressive neuronal degeneration. Finally, we offer perspectives on intensive avenues for future research.</p><p>\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 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725476","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}
引用次数: 0
Neural Stem Cell-Derived Extracellular Vesicles for Advanced Neural Repair 神经干细胞衍生的细胞外囊泡用于高级神经修复
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-30 DOI: 10.1111/jnc.70170
Eduardo H. Moretti, Ally L. Y. Lin, Luca Peruzzotti-Jametti, Stefano Pluchino, Sabah Mozafari
{"title":"Neural Stem Cell-Derived Extracellular Vesicles for Advanced Neural Repair","authors":"Eduardo H. Moretti,&nbsp;Ally L. Y. Lin,&nbsp;Luca Peruzzotti-Jametti,&nbsp;Stefano Pluchino,&nbsp;Sabah Mozafari","doi":"10.1111/jnc.70170","DOIUrl":"https://doi.org/10.1111/jnc.70170","url":null,"abstract":"<p>The limited regenerative capacity of the central nervous system (CNS) severely hinders treatment of neurodegenerative and neuroinflammatory diseases. These conditions, frequently exacerbated by aging, share common hallmarks such as neuroinflammation, demyelination, and neuronal loss. While neural stem cells (NSCs) hold great therapeutic promise due to their paracrine effects, including extracellular vesicle (EV) release, direct transplantation presents significant challenges. This review focuses on NSC-derived EVs as a novel therapeutic strategy, as we explore their multimodal mechanisms in modulating neuroinflammation, promoting neurogenesis, and restoring cellular bioenergetics through the delivery of bioactive molecules and mitochondrial transfer. Recent advances in NSC-EV-based therapies for age-associated neurodegenerative diseases are highlighted, along with key challenges in EV production, preservation, and targeted delivery. Finally, we outline future directions for translating this promising approach into effective clinical treatments.</p><p>\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 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725479","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}
引用次数: 0
MGlu5 Dependent Mitochondrial Translocation of PKCδ: A Mechanism Raising Astrocytic Oxidative Metabolism in Response to Extracellular Glutamate MGlu5依赖的PKCδ线粒体易位:细胞外谷氨酸响应中星形细胞氧化代谢的机制
IF 4 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-30 DOI: 10.1111/jnc.70163
Kiavasch M. N. Farid, Rodrigo Lerchundi, Christine R. Rose, Amin Derouiche
{"title":"MGlu5 Dependent Mitochondrial Translocation of PKCδ: A Mechanism Raising Astrocytic Oxidative Metabolism in Response to Extracellular Glutamate","authors":"Kiavasch M. N. Farid,&nbsp;Rodrigo Lerchundi,&nbsp;Christine R. Rose,&nbsp;Amin Derouiche","doi":"10.1111/jnc.70163","DOIUrl":"https://doi.org/10.1111/jnc.70163","url":null,"abstract":"<p>Synaptic activity imposes high demands of local energy production on astrocytes. However, the (an)aerobic pathways and fuel for generation of energy equivalents in astrocytes are still debated. Also, mechanisms to ensure rapid metabolic adaptation to bouts of neuronal activity have not been sufficiently explored. Here, we show a mechanism in astrocytes linking extracellular glutamate to upregulation of oxidative phosphorylation. We stimulated primary astrocytes with glutamate, and applied fluorescent immunocytochemistry with anti-protein kinase Cδ (PKCδ), anti-pyruvate dehydrogenase (PDH) and anti-phospho-PDH antibodies, and object oriented image analysis. Glutamate induces mitochondrial translocation of PKCδ and subsequent activation of the mitochondrial enzyme PDH—the point-of-no-return in the utilization of carbohydrates. Using the specific mGlu5 antagonist 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), the metabotropic glutamate receptor 5 (mGlu5) was identified as the key receptor inducing mitochondrial PKCδ translocation and PDH activation. We demonstrate by luminometric ATP assay and subtype-specific inhibitors of PKC and mGlu5 that the distinct initial drop in intracellular ATP following glutamate application is counteracted by the mGlu5/PKCδ-dependent mitochondrial activation. mGlu5 inhibition decreases ATP production also in astrocytes in the acute brain slice. Collectively, these findings reveal that astrocytes possess a potential for oxidative phosphorylation that can be stimulated by extracellular glutamate and the mGlu5/PKCδ/PDH axis, suggesting targets for pathologies involving excess glutamate. This also focuses the issue of activity-induced glia-neuronal metabolic interaction on perisynaptic energetics and the glia-<i>synaptic</i> microenvironment. Up-regulation of astrocytic metabolism via the mGlu5/PKCδ/PDH axis may affect only those perisynaptic astrocyte processes (PAPs) close to the active synapse(s), leaving other astrocyte domains and the whole cell unchanged.\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 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740266","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}
引用次数: 0
Orexin/Hypocretin Modulates Neuroinflammatory Response to LPS in a Sex and Brain-Region Specific Manner in Young Rats 食欲素/下丘脑分泌素以性别和脑区特异性方式调节年轻大鼠对LPS的神经炎症反应
IF 4.2 3区 医学
Journal of Neurochemistry Pub Date : 2025-07-29 DOI: 10.1111/jnc.70175
M. A. Frick, J. L. Woodruff, Y. M. Caudillo, K. E. Pikel, J. V. Rehm, N. Maciejewska, C. A. Grillo, L. P. Reagan, J. R. Fadel
{"title":"Orexin/Hypocretin Modulates Neuroinflammatory Response to LPS in a Sex and Brain-Region Specific Manner in Young Rats","authors":"M. A. Frick,&nbsp;J. L. Woodruff,&nbsp;Y. M. Caudillo,&nbsp;K. E. Pikel,&nbsp;J. V. Rehm,&nbsp;N. Maciejewska,&nbsp;C. A. Grillo,&nbsp;L. P. Reagan,&nbsp;J. R. Fadel","doi":"10.1111/jnc.70175","DOIUrl":"https://doi.org/10.1111/jnc.70175","url":null,"abstract":"<p>Neuroinflammation has emerged as a contributing mechanism in age-related cognitive decline (ARCD), Parkinson's disease (PD), obesity, sleep disorders, and autoimmune disorders. Orexin/hypocretin, a neuropeptide expressed in the lateral hypothalamus (LH), has well-established roles in homeostatic processes, such as energy metabolism, food intake, sleep, and wakefulness. Our laboratory and others have shown that orexin expression decreases with age, and this age-related orexin decline is exacerbated in disease states. Additionally, it has recently been shown that orexin possesses anti-inflammatory and neuroprotective properties. Based on these observations, we hypothesize that orexin is modulating neuroinflammation in brain regions that are critical in the development of ARCD. To test this hypothesis, we used lentiviral gene transfer to downregulate orexin expression in male and female young rats to mimic age-related orexin deficiency and examined neuroinflammatory responses to peripheral administration of lipopolysaccharide (LPS). We found a significant reduction of basal forebrain (BF) microglial complexity and plasma BDNF in both males and females following orexin downregulation. Notably, orexin downregulation blocked the capacity of the neuroinflammatory system to respond to LPS. These results demonstrate that neuroinflammatory responses are dependent on orexin signaling, and this system becomes dysfunctional in aging in a sex-dependent manner.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716593","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}
引用次数: 0
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