Neurochemical Research最新文献

{"title":"Compatibility of Acorus tatarinowii Schott and Polygala tenuifolia Willd. alleviate Alzheimer’s disease through regulating Nos2-mediated calcium signaling pathway","authors":"Bingling Zhou,&nbsp;Xiao Wu,&nbsp;Junli Wang,&nbsp;Lijuan Li,&nbsp;Huifang Xu,&nbsp;Wei Shao","doi":"10.1007/s11064-026-04757-z","DOIUrl":"10.1007/s11064-026-04757-z","url":null,"abstract":"<div><p>Herb pair of Acorus tatarinowii Schott (ATS) and Polygala tenuifolia Willd. (PTW) is a classic drug pair in the treatment of Alzheimer’s disease (AD), However, the mechanism by which the drug pair acts on AD is currently unknown. To address this, we constructed a PC12 cellular AD model using amyloid-beta peptide (Aβ) (25–35), follow by treating with different concentrations of ATS and PTW alone or their combination (1:1). The cell viability and Aβ-40, Aβ-42 and AQP4 expression were detected. In addition, RNA-sequencing combined with network pharmacology was performed to investigate the action mechanism of ATS and PTW, and the results were validated using in vitro experiments. The results showed that at drug-acting concentrations less than 100 mg/L, both single-agent and combined treatments of ATS and PTW increased the protective effects on PC12 cell, and the herb pair was superior to single-agent. In addition, both single-agent and combined treatments of ATS and PTW (at concentration of 100 mg/L) decreased Aβ-40, Aβ-42 and AQP4 expression compared with AD model. Further RNA-sequencing combined with network pharmacology analysis suggested that the underline action mechanism might be associated with Nos2-mediated calcium signaling pathway regulated. In vitro validation experiments showed that <i>Nos2</i> overexpression increase the levels of Aβ-40, Aβ-42, AQP4, p-Tau, CaM, and p-CaMKII, which were reversed by the combination treatment of ATS and PTW. In conclusion, this work indicates that ATS and PTW combination might alleviate an Aβ-induced cellular model through regulating <i>Nos2</i> - mediated calcium signaling pathway.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830104","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":"Ginsenoside Rh2 Protects Against Glutamate-Induced Neurotoxicity in PC12 Cells via Activation of the VEGF-mediated PI3K/Akt/mTOR Signaling Pathway","authors":"Chun-Yue Zhang,&nbsp;Chang Liu,&nbsp;Liang-Jing Liu,&nbsp;Jian-Ming Yang,&nbsp;Li-Xia Shen,&nbsp;Zhi-Gang Wu","doi":"10.1007/s11064-026-04763-1","DOIUrl":"10.1007/s11064-026-04763-1","url":null,"abstract":"<div><p>Ginsenoside Rh2 (GRh2), a major active component of red ginseng, exhibits significant neuroprotective effects against glutamate-induced excitotoxicity in differentiated PC12 cells. This study found that GRh2 concentration-dependently reversed the loss of cell viability caused by glutamate. It effectively attenuated key pathological events, including intracellular calcium overload, reactive oxygen species accumulation, and mitochondrial membrane potential collapse. Furthermore, GRh2 enhanced synaptic plasticity, as evidenced by improved neurite morphology and increased levels of the synaptic markers neurogranin and neuromodulin. Mechanistic investigations revealed that GRh2 upregulated vascular endothelial growth factor (VEGF) expression and subsequently activated the PI3K/Akt/mTOR signaling pathway. This activation led to increased expression of synaptic proteins (PSD-95 and synaptophysin), an elevated Bcl-2/Bax ratio. Critically, the specific VEGF inhibitor SU11248 and PI3K inhibitor LY294002 abolished all the protective effects of GRh2, confirming the indispensable role of the VEGF/PI3K/Akt/mTOR axis. These results indicate that GRh2 alleviates glutamate-induced neurotoxicity by activating the VEGF-mediated PI3K/Akt/mTOR pathway, thereby improving mitochondrial function, inhibiting oxidative stress and apoptosis, and promoting synaptic integrity. This work provides novel molecular insights into the neuroprotective mechanism and potential of GRh2.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830087","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":"Glutathione as a Potential Neuroprotectant Against MDMA-Induced Oxidative Stress, Neuroinflammation, and Apoptosis in the Rat Brain","authors":"Oyedayo Phillips Akano,&nbsp;Goodness Olatinwo,&nbsp;Moses Agbomhere Hamed,&nbsp;David Tolulope Oluwole,&nbsp;Ayomide Jonathan Jegede,&nbsp;Ayodeji Folorunsho Ajayi","doi":"10.1007/s11064-026-04764-0","DOIUrl":"10.1007/s11064-026-04764-0","url":null,"abstract":"<div><p>3,4-Methylenedioxymethamphetamine (MDMA), widely misused for its euphoric and stimulant properties, induces overt neurotoxicity in rodents and non-human primates and is associated with profound neurochemical and structural brain alterations. Its deleterious effects are primarily mediated through oxidative stress, neuroinflammatory responses, and apoptotic pathways. Glutathione, a crucial endogenous antioxidant, has been proposed as a potential neuroprotective agent capable of mitigating MDMA-induced cerebral damage.Sixty adult male Wistar rats were randomly assigned to six experimental groups and administered oral treatments for 56 days: MDMA (5 mg/kg or 15 mg/kg), glutathione (15 mg/kg), or their combinations. After treatment, brain tissues were harvested and evaluated for oxidative stress biomarkers (8-OHdG, MDA, GPx, GSH, GST, SOD), pro-inflammatory cytokines (MPO, NF-κB, TNF-α), ion transport enzymes (Na⁺/K⁺ ATPase, Ca²⁺ ATPase), neurotransmitter levels (dopamine, serotonin, AChE), and the apoptotic marker caspase-3. Histological analysis of the hippocampus was conducted to assess structural integrity. MDMA administration led to significant elevations in MDA and 8-OHdG, reductions in antioxidant enzymes (GPx, GST, GSH, SOD), upregulation of inflammatory mediators (MPO, NF-κB, TNF-α), and disruption of ion homeostasis via altered Na⁺/K⁺ ATPase and Ca²⁺ ATPase activities. Neurotransmitter imbalances were observed, characterized by increased AChE and serotonin levels and decreased dopamine. Caspase-3 activity was markedly elevated, indicating enhanced apoptosis. Co-administration of glutathione at low MDMA doses ameliorated these effects, restoring antioxidant defenses, suppressing inflammation, and preserving hippocampal architecture. However, its protective efficacy was notably diminished at higher MDMA concentrations. Glutathione confers partial neuroprotection against MDMA-induced neurotoxicity, particularly under moderate exposure conditions. Its antioxidative capacity contributes to the restoration of redox equilibrium and cellular integrity. Nonetheless, under high-dose MDMA exposure, the therapeutic potential of glutathione is limited, suggesting the necessity for complementary interventions targeting excitotoxicity and mitochondrial dysfunction.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829326","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":"Sex-Specific Differences in Amino Acids and Neurotransmitters in Multiple Sclerosis Patients Compared to Non-Neuroinflammatory Controls: A Retrospective Case-Control Study","authors":"Philip Meier,&nbsp;Sandra Glasmacher,&nbsp;Anke Salmen,&nbsp;Andrew Chan,&nbsp;Jürg Gertsch","doi":"10.1007/s11064-026-04766-y","DOIUrl":"10.1007/s11064-026-04766-y","url":null,"abstract":"<div><p>Multiple sclerosis (MS) is an immune-mediated chronic neuroinflammatory and neurodegenerative disorder. Inflammation in MS disrupts the barriers between blood and central nervous system and affects transport and diffusion of metabolites between blood and cerebrospinal fluid (CSF). In this exploratory retrospective case–control study, we used targeted metabolomics to evaluate differences in serum and CSF amino acid and neurotransmitter levels between patients with MS (<i>n</i> = 73) and non-neuroinflammatory controls (<i>n</i> = 78). The influence of patient characteristics, including sex, age, disease duration, severity and treatment status, was also analzyed. Although no significant differences in serum and CSF metabolite levels were found between MS and control patients, a stratification by sex uncovered significantly reduced metabolites in male MS patients compared to male controls in CSF but not in serum. While in male MS patients CSF histidine levels were decreased, female MS patients showed increased levels. Further, sex-specific associations of amino acids and neurotransmitters with disease duration and disability were observed. MS patients exhibited enhanced positive correlations between CSF and serum analyte levels. In serum, only a few amino acids, along with serotonin and glutathione, were associated with MS disease duration. Overall, this study suggests that targeted metabolomics of selected analytes in matched CSF and serum samples is a valuable approach for assessing alterations in CSF–serum metabolite associations in MS, as well as sex-specific imbalances between excitatory and inhibitory neurotransmitters across disease duration. Our findings further highlight the importance of considering sex as a key biological factor in MS.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-026-04766-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829622","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":"Hippocampal Lipocalin-2 in T2DM Associated Neurodegeneration: A Therapeutic Perspective","authors":"Baivhabee Panigrahy,&nbsp;Arghya Mukherjee,&nbsp;Santosh Singh","doi":"10.1007/s11064-026-04765-z","DOIUrl":"10.1007/s11064-026-04765-z","url":null,"abstract":"<div><p>The hippocampus is a brain region critically involved in learning and memory and is particularly vulnerable to metabolic and inflammatory stresses. Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is associated with cognitive decline and structural alterations in the hippocampus, a condition commonly referred to as diabetic encephalopathy (DE). Lipocalin-2 (LCN-2), an acute-phase glycoprotein involved in iron homeostasis and innate immunity, has emerged as an important mediator of neuroinflammation and glial reactivity in the central nervous system. Although LCN-2 has been implicated in several neurodegenerative disorders, its region-specific role in hippocampal dysfunction during T2DM remains incompletely understood. Unlike prior reviews that address DE broadly, the present review synthesizes current experimental and clinical evidence linking hippocampal LCN-2 to neuroinflammation, synaptic dysfunction, and cognitive impairment in T2DM, with particular emphasis on astrocyte-microglia crosstalk. We further discuss the potential therapeutic strategy of selectively modulating LCN-2 signaling as an alternative to broad anti-inflammatory approaches, along with its potential advantages and limitations.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829620","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":"Interleukin-17A as a Potential Mediator in Inflammatory Mechanisms of Insomnia","authors":"Ellen M. S. Xerfan,&nbsp;Monica L. Andersen,&nbsp;Anamaria S. Facina,&nbsp;Sergio Tufik,&nbsp;Jane Tomimori","doi":"10.1007/s11064-026-04758-y","DOIUrl":"10.1007/s11064-026-04758-y","url":null,"abstract":"<div><p>The interaction between immune cytokines and sleep can be bidirectional, and the circadian rhythm balance has a crucial role to the immune and inflammatory regulation. Insomnia is a prevalent sleep disorder, in which occur modifications in immune expression, including the cytokines pattern. Some somnogenic cytokines, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) have been classically recognized for their direct association with sleep behavior and circadian alignment. More recent evidence has increasingly implicated the role of IL-17A in sleep disturbances and neuroinflammation. However, its specific relationship with insomnia disorder remains underexplored. This cytokine is considered as a relevant immune component in the pathways involved in inflammatory and autoimmune issues. Previous and rare studies on the behavior of IL-17A in insomnia related with comorbid disease suggested that increased IL-17A serum levels may be linked to poor sleep quality. We suggest that further experimental and clinical studies examining the role of IL-17A should shed more light in its relationship with insomnia; and on the immunological and neuroinflammatory associations with this sleep disorder.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829191","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":"Lamotrigine Improves Spatial Learning and Attenuates AD-Related Pathology in APP/PS1 Mice, with Possible Involvement of the cAMP/PKA/CREB Pathway","authors":"Xiaoyu Zheng,&nbsp;Ping Chen,&nbsp;Dongyue Li,&nbsp;Weijie Li,&nbsp;Jiancheng Liao,&nbsp;Maoying Zhang","doi":"10.1007/s11064-026-04767-x","DOIUrl":"10.1007/s11064-026-04767-x","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is characterized by impaired spatial learning functions, amyloid-β accumulation, tau hyperphosphorylation, and neuroinflammation. Antiepileptic drugs such as lamotrigine have shown promise in improving brain functions in AD, but the underlying mechanisms remain unclear. This study aimed to evaluate the therapeutic effects of lamotrigine in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and elucidate the underlying molecular mechanisms using integrated transcriptomic and metabolomic analyses. APP/PS1 mice were treated with lamotrigine from 3 months of age, and spatial learning performance was assessed using the Morris water maze test. Histological and molecular changes were evaluated through hematoxylin and eosin staining, Western blotting, ELISA, and immunohistochemistry. High-throughput RNA sequencing and untargeted metabolomics were performed to explore differentially expressed genes, metabolites, and enriched signaling pathways. Western blot validation and pharmacological inhibition were used to verify pathway involvement. Lamotrigine treatment significantly improved spatial learning performance, ameliorated neuronal degeneration, and decreased Aβ1 levels and tau phosphorylation in the brains of APP/PS1 mice. Inflammatory markers and glial activation were also markedly suppressed. Multi-omics analysis revealed alterations in key pathways related to synaptic plasticity, lipid metabolism, and autophagy. Notably, both omics data and protein validation highlighted the cAMP/PKA/CREB pathway as a potentially relevant pathway. Co-administration of the PKA inhibitor H89 abolished lamotrigine-induced upregulation of p-CREB and BDNF, supporting the involvement of this pathway. Lamotrigine improves spatial learning and attenuates AD-related pathology in APP/PS1 mice, possibly through modulation of the cAMP/PKA/CREB signaling pathway, highlighting its potential as a candidate for further investigation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829623","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":"FTDP-17T Mutations Promote Formation of Phosphorylated FTDP-17T TAU Oligomers That Cause Degeneration of Dopaminergic and Hippocampal Neurons via Activating ER Stress and Mitochondrial Pro-apoptotic Cascades","authors":"Hung-Li Wang,&nbsp;Yi-Hsin Weng,&nbsp;Ching-Chi Chiu,&nbsp;Wan-Shia Chen,&nbsp;Shu-Yu Liu,&nbsp;Tu-Hsueh Yeh","doi":"10.1007/s11064-026-04761-3","DOIUrl":"10.1007/s11064-026-04761-3","url":null,"abstract":"<div><p>Heterozygous missense mutations of TAU cause frontotemporal dementia with parkinsonism linked to chromosome 17 with tau pathology (FTDP-17T). FTDP-17T neurodegeneration of hippocampal and substantia nigra dopaminergic cells causes dementia and parkinsonism motor deficits. FTDP-17T cellular model of mutant TAU-expressing differentiated dopaminergic or hippocampal neurons was utilized to test hypothesis that FTDP-17T (R5H), (N279K), (K298E), (P301S), (K317M) and (G389R) TAUs located in different domains of TAU cause neurodegeneration with the same pathomechanism. (R5H), (N279K), (K298E), (P301S), (K317M) and (G389R) TAUs caused degeneration of dopaminergic or hippocampal neurons via mutation-induced gain-of-neurotoxicity. (R5H), (N279K), (K298E), (P301S), (K317M) and (G389R) mutations promoted Ser²⁰²/Ser³⁹⁶/Ser⁴⁰⁴ phosphorylations of TAU and formation of phospho-FTDP-17T TAU^{Ser202/Ser396/Ser404} oligomers in dopaminergic or hippocampal neurons. GSK-3β inhibitor AR-A014418 completely blocked (R5H), (N279K), (K298E), (P301S), (K317M) and (G389R) TAUs-induced neurotoxicity by preventing (R5H), (N279K), (K298E), (P301S), (K317M) and (G389R) mutations-augmented Ser²⁰²/Ser³⁹⁶/Ser⁴⁰⁴ phosphorylations and genesis of phospho-FTDP-17T TAU^{Ser202/Ser396/Ser404} oligomers. Phospho-(R5H), phospho-(N279K), phospho-(K298E), phospho-(P301S), phospho-(K317M) or phospho-(G389R) TAU^{Ser202/Ser396/Ser404} oligomers were found in ER of dopaminergic or hippocampal neurons and activated ER stress, UPR and ER stress apoptotic signaling. Overexpression of mitochondrial phospho-FTDP-17T TAU^{Ser202/Ser396/Ser404} oligomers caused mitochondrial malfunction via depolarizing mitochondrial membrane potential and oxidative damage by increasing ROS. Phospho-FTDP-17T TAU^{Ser202/Ser396/Ser404} oligomers-evoked upregulation of Noxa, Bim or Puma and mitochondrial defect and oxidative stress excited mitochondrial pro-apoptotic pathway. Our results suggest that shared pathomechanism underlying FTDP-17T (R5H), (N279K), (K298E), (P301S), (K317M) and (G389R) TAUs-induced neurotoxicity is mutation-augmented GSK-3β-mediated Ser²⁰²/Ser³⁹⁶/Ser⁴⁰⁴ phosphorylations and generation of phospho-FTDP-17T TAU^{Ser202/Ser396/Ser404} oligomers, which cause neurodegeneration by stimulating ER stress and mitochondrial pro-apoptotic cascades.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759318","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":"Electroacupuncture Stimulation of the Head Motor Area Alleviates Brain Cell Pyroptosis and Neurobehaviors in Stroke Rats Through the NF-κB/NLRP3 Signaling Axis","authors":"Zhen Hu,&nbsp;Zhijun Yong","doi":"10.1007/s11064-026-04733-7","DOIUrl":"10.1007/s11064-026-04733-7","url":null,"abstract":"<div>\u0000 \u0000 <p>Electroacupuncture (EA), a combination of acupuncture and electrical stimulation, is an efficient therapy for stroke. The paper intends to investigate the impact of EA stimulation of the head motor area on the neurological function of stroke rats and the underlying mechanism. An MCAO rat model was developed and intervened with EA, the NLRP3 activator Nigericin, and the NF-κB activator PMA. Motor function, coordination ability, neurological dysfunction, infarct volume, histopathological changes, and cortical nerve cell alterations were assessed using the Basso Beattie Bresnahan score, balance beam test, neurobehavioral score, and TTC, H&amp;E, and Nissl stainings. Neuroinflammation degree, inflammatory cytokine levels, and cortical expression of NF-κB, NLRP3, Cleaved Caspase-1, and GSDMD-N were assessed using immunohistochemistry, immunofluorescence, ELISA, and western blot. MCAO rats treated with EA showed improved motor function and neurobehaviors. EA inhibited NF-κB/NLRP3-mediated brain cell pyroptosis and neuroinflammation, demonstrated by decreased cortical NF-κB expression and phosphorylation, NLRP3, Cleaved Caspase-1/Pro-Caspase-1 and GSDMD-N/GSDMD expression, and GSDMD-N-positive cell count, reduction of activated microglia (Iba-1⁺ and Iba-1⁺CD68⁺) and astrocytes (GFAP⁺), decreased IL-1β and IL-18, IL-6, and tumor necrosis factor-α levels, and increased IL-10 and transforming growth factor-β levels. These findings suggest that EA may improve motor function and neurobehaviors in MCAO rats by inhibiting the NF-κB/NLRP3 pathway. Conversely, activation of the NF-κB/NLRP3 pathway attenuated the ameliorative effects of EA. EA stimulation of the head motor area mitigated brain cortical pyroptosis and neuroinflammation via NF-κB/NLRP3 pathway suppression, thereby ameliorating motor function and neurobehaviors in MCAO rats.</p>\u0000 </div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759304","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":"Ca2+ Signaling Enables Growth Hormone Secretion from Cultured Mice Pituitary Somatotrophs, Facilitating Outgrowth in Hypothalamic Neuron","authors":"Samuel Shin,&nbsp;Samshritha Bikki,&nbsp;Kimberly Byrnes,&nbsp;Bidhan C. Bandyopadhyay","doi":"10.1007/s11064-026-04755-1","DOIUrl":"10.1007/s11064-026-04755-1","url":null,"abstract":"<div><p>The hypothalamus regulates anterior pituitary (AP) hormone release via the hypophyseal portal system by secreting specific releasing and inhibiting peptide hormones. Growth hormone (GH) secretion from pituitary somatotrophs (PS) is regulated by a cholinergic mechanism that induces calcium (Ca²⁺) signaling, which in turn triggers vesicular exocytosis and GH release. Given that the transient receptor potential canonical channel 3 (TRPC3) regulates vesicle exocytosis in endocrine and neuroendocrine cells, we investigated its role in GH release from somatotrophs and whether GH release could support neuronal growth in the hypothalamus. Activation of TRPC3 by the diacylglycerol analog, 1-oleoyl-2-acetyl-sn-glycerol (OAG), resulted in a rapid increase in intracellular Ca²⁺ ([Ca²⁺]_i) in wild type (WT) PS, attenuated by the TRPC3 inhibitor Pyr10, or by the knockout of TRPC3. ELISA assay confirmed that OAG exposure triggered GH release in WT PS. Conditioned media from OAG-stimulated PS promoted significant neurite outgrowth in hypothalamic neuronal cultures, suggesting a role for released GH in this process. Exposure of PS to H₂O₂-induced oxidative damage enhanced store-operated Ca²⁺ entry (SOCE) compared to control cells. Electrophysiological characterization revealed that somatotrophs under increased reactive oxygen species (ROS) conditions exhibited elevated SOCE, whereas cells under more native conditions exhibited receptor-operated Ca²⁺ entry. Furthermore, media from oxidative-stressed PS cultures, followed by the OAG exposure, induced neurite outgrowth, suggesting TRPC3 activation may provide an alternative pathway after ROS-induced damage in GH release. These findings indicate that Ca²⁺ signaling activation may promote GH secretion from control and ROS-induced AP cells, potentially leading to neurite outgrowth in hypothalamic cells. This study may provide insights into restoring neuronal connectivity following brain injury.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div><p>The methodological diagram illustrates TRPC3-activation by OAG in control and ROS-activated (+H₂O₂) pituitary somatotroph cultures, inducing GH secretion into the supernatant. These supernatants were then applied to cultured hypothalamic neurons, resulting in neurite growth. The panel above depicts the overall concept of GH release supporting a local activation mechanism to ensure neuronal outgrowth.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737973","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}