Neurochemical Research最新文献

{"title":"Δ9-Tetrahydrocannabinol Modulates Hippocampal Neurogenesis in Female Wistar Rats: Interaction with Estradiol","authors":"Duarte R. Carvalhinho,&nbsp;Sandra I. Marques,&nbsp;Sandra Leal,&nbsp;Bruno M. Fonseca,&nbsp;José P. Andrade,&nbsp;Susana I. Sá","doi":"10.1007/s11064-026-04857-w","DOIUrl":"10.1007/s11064-026-04857-w","url":null,"abstract":"<div><p>The endocannabinoid system (ECS) plays a key role in regulating neurogenesis and inflammatory processes in the brain. The increasing prevalence of Cannabis use among women highlights the importance of understanding sex-specific effects of cannabinoids, particularly in the context of hormonal interactions. This study aimed to investigate the effects of delta-9-tetrahydrocannabinol (THC) and estradiol benzoate (EB) on adult hippocampal neurogenesis (AHN) and inflammation in ovariectomized female Wistar rats. Sixteen rats were allocated to four experimental groups receiving THC, EB, both treatments, and vehicle. Immunohistochemical analyses were conducted to evaluate markers of proliferation (Ki-67), neurogenesis (doublecortin and PSA-NCAM), cannabinoid receptor expression (CB1), and inflammation (COX-2 and TNF-α) in the hippocampal formation. The administration of THC significantly increased Ki-67 immunoreactivity, suggesting enhanced cell proliferation. A trend toward increased doublecortin expression was observed, particularly in EB-treated animals. THC also modulated CB1 receptor expression, with significant increases in the dentate gyrus and hilus following combined THC and EB treatment. Furthermore, THC reduced inflammatory markers, with region-dependent decreases in COX-2 and TNF-α expression. These findings indicate that THC influences markers associated with hippocampal cell proliferation, neurogenesis, cannabinoid signaling and inflammation in female rats, and that some of these effects depend on estradiol status. The interaction between cannabinoids and gonadal hormones may represent an important mechanism underlying sex-specific neurobiological responses and suggests potential targets for therapeutic intervention in neuropsychiatric disorders.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696986","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":"Comparative Analysis of LPS/IFN-γ and LPS/ATP-Induced Inflammatory Models in BV2 Microglia","authors":"Xinfeng Zhang,&nbsp;Zhuo Lian,&nbsp;Sijie Lei,&nbsp;Tanhui Yi,&nbsp;Shuyin Zhao,&nbsp;Mingxiang Liu,&nbsp;Yiling Gui,&nbsp;Chengyi Zhu,&nbsp;Qian Xie,&nbsp;Rong Ma","doi":"10.1007/s11064-026-04853-0","DOIUrl":"10.1007/s11064-026-04853-0","url":null,"abstract":"<div><p>The selection of appropriate in vitro inflammatory models is critical for mechanistic studies of neuroinflammation and the screening of anti-inflammatory therapeutics. Lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ) and LPS combined with adenosine triphosphate (ATP) are widely used to induce microglial inflammation; however, their distinct phenotypic characteristics and optimal applications have not been systematically compared. In this study, we combined transcriptomic profiling with functional assays to compare these two inflammatory paradigms in BV2 microglia. Our results showed that both models activated the chemokine–cytokine inflammatory network and induced the production of inflammatory mediators and chemokines, but exhibited distinct molecular and functional biases. LPS/IFN-γ stimulation preferentially upregulated genes such as <i>Lcn2</i>, <i>Ccl2</i>, <i>Upp1</i>, and <i>Pim2</i>, which are associated with innate immune activation, chemokine-mediated inflammatory responses, and cell survival signaling, and was accompanied by marked increases in NO and TNF-α production. In contrast, the LPS/ATP model preferentially upregulated genes associated with ECM/cell adhesion, inflammatory and cellular homeostatic regulation, oxidative stress, and calcium-dependent secretion, including <i>Thbs1</i>, <i>Thbd</i>, <i>Srxn1</i>, <i>Syt7</i>, and <i>Procr</i>. Functionally, this model exhibited more pronounced IL-1β maturation and release, relatively lower NO production, and greater mitochondrial dysfunction and cell injury. Pharmacological inhibition of NLRP3 with MCC950 significantly attenuated ATP-induced IL-1β maturation, supporting the involvement of the NLRP3 inflammasome in the LPS/ATP model. Overall, the LPS/IFN-γ model is more suitable for investigating the NO/iNOS–TNF-α axis, IFN-γ-mediated synergistic pro-inflammatory responses, and classical pro-inflammatory activation, as well as for screening anti-inflammatory agents. In contrast, the LPS/ATP model is more appropriate for studying IL-1β maturation and release, NLRP3 inflammasome activation, mitochondrial damage, and inflammation-related cell death, as well as for screening inflammasome inhibitors. Our findings provide an empirical framework for rational model selection in microglial inflammation research.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683070","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":"Carboxypeptidase E Alleviates Depressive-Like Behaviors in Mice by Regulating BDNF/Nrf2 Axis-Mediated Ferroptosis","authors":"Wenjie Li,&nbsp;Fanying Meng,&nbsp;Jizhen Li,&nbsp;Li Lv","doi":"10.1007/s11064-026-04823-6","DOIUrl":"10.1007/s11064-026-04823-6","url":null,"abstract":"<div><p>Carboxypeptidase E (CPE) may be a therapeutic target for depression. This study investigated the mechanistic insights into the possible regulatory role of CPE in ferroptosis in a mouse model of chronic unpredictable mild stress (CUMS)-induced depression. One week before CUMS exposure, mice received injections of adeno-associated virus-CPE. One week after CUMS induction, the Nrf2 inhibitor ML385 was administered. Behavioral tests were performed 3 weeks after CUMS induction. Ionized calcium-binding adapter molecule 1-positive cells and inflammatory cytokine levels in the CA1 region were assessed by immunofluorescence and ELISA. Hippocampal pathological and neuronal damage were evaluated using H&amp;E and Nissl staining. Additionally, brain-derived neurotrophic factor (BDNF)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, ferroptosis markers, oxidative stress indices, glutathione peroxidase 4 (GPX4), and Fe2+ levels were measured using western blot, RT-qPCR, and biochemical assays. CPE overexpression alleviated CUMS-induced depression-like behaviors and hippocampal damage in mice. CPE overexpression reduced microglial activation, neuronal degeneration, and pro-inflammatory factors. It also attenuated oxidative stress by decreasing malondialdehyde, reactive oxygen species, and lactate dehydrogenase while elevating superoxide dismutase and glutathione-S-transferase activities. Mechanistically, CPE activated the BDNF/Nrf2 axis, increased GPX4 activity, suppressed acyl-CoA synthetase long chain family member 4 expression, and reduced iron accumulation. All protective effects of CPE overexpression were reversed by ML385. CPE overexpression activates the BDNF/Nrf2 signaling axis to inhibit ferroptosis, thereby reducing neuroinflammation and depression-like behaviors in mice. This work further clarifies the pathogenesis of depression, enriches pathophysiological theories, and provides key experimental evidence for early intervention and target development.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676905","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":"Striatal Dopamine D2 Receptors Contribute to N-Ethylpentylone-Induced Arousal in Mice","authors":"Cheng-Teng Fan,&nbsp;Jing-Ya Wang,&nbsp;Hong Qian,&nbsp;Shang-Qi Tang,&nbsp;Zhi-Gang Zhong,&nbsp;Yu-Rong Zhang,&nbsp;Shui-Qing Zheng,&nbsp;Mei-Hong Qiu,&nbsp;Yu-Lan Rao,&nbsp;Zhi-Ru Xu","doi":"10.1007/s11064-026-04851-2","DOIUrl":"10.1007/s11064-026-04851-2","url":null,"abstract":"<div><p>Drug-induced sleep disruption exacerbates addiction, causes long-term cognitive and emotional deficits, and becomes a key relapse trigger. However, despite the potent stimulant and hallucinogenic effects of synthetic cathinones, their impact on sleep–wake behaviors remains unstudied, and the role of striatal dopamine D2 receptors in mediating psychostimulant-induced arousal has yet to be identified. This study aimed to elucidate the mechanisms underlying N-ethylpentylone (NEP, a second-generation synthetic cathinone) induced alterations in sleep-wake behavior, specifically investigating the relative contributions of dopamine receptors (DARs) and serotonin receptors. Using the in vitro PRESTO-Tango assay, we characterized the interactions between NEP and various DARs, revealing that NEP produced the strongest β-arrestin recruitment response at dopamine D2 receptor (D2R) among the dopamine receptor subtypes tested. In vivo electroencephalogram/electromyogram (EEG/EMG) recordings in wild-type (WT) mice demonstrated that NEP dose-dependently promoted wakefulness and reduced non-rapid eye movement (NREM) sleep. This was accompanied by decreased θ-band and increased α-band power spectral density during wakefulness. Pharmacological blockade of D2R with haloperidol significantly attenuated NEP-induced wake promotion and partially reversed the aberrant EEG oscillations. Crucially, conditional knockout of D2R specifically in striatum markedly diminished the wake-promoting effects of NEP. In contrast, pharmacological blockade of the serotonin 2 A receptor (5-HT2AR) with 1 mg/kg MDL100907 did not significantly alter NEP-induced sleep–wake changes. Furthermore, immunofluorescence staining analysis confirmed that D2R blockade effectively reversed NEP-induced c-Fos expression in the striatum. Together, these findings demonstrated striatal D2R played a critical role in NEP-induced arousal.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663279","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":"Nicotine in Neurodegenerative and Neuropsychiatric Disorders: Mechanisms and Clinical Evidence","authors":"Geir Bjørklund,&nbsp;Leonard Gurgas,&nbsp;Tony Hangan","doi":"10.1007/s11064-026-04845-0","DOIUrl":"10.1007/s11064-026-04845-0","url":null,"abstract":"<div><p>Nicotine, a psychoactive compound primarily known for its role in tobacco addiction, has attracted increasing interest for its neuromodulatory and neuroprotective properties. Acting predominantly through nicotinic acetylcholine receptors, nicotine influences multiple neurotransmitter systems, modulates neuroinflammation, and supports synaptic plasticity. These mechanisms may be therapeutically relevant in disorders characterized by neurodegeneration or disrupted neurocircuitry, including Parkinson’s disease, Alzheimer’s disease, schizophrenia, attention-deficit/hyperactivity disorder, depression, and post-traumatic stress disorder. This review critically examines the current state of preclinical and clinical evidence, with particular attention to receptor subtype activity, cognitive and emotional modulation, and human trial data. Although nicotine’s addictive potential and receptor desensitization remain concerns, advances in selective ligands offer new therapeutic avenues. By consolidating mechanistic insights and disease-specific data, this review highlights both the promise and challenges of developing nicotinic-based therapeutics for brain disorders.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663203","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":"Thioredoxin-1 in the SNpc Regulates Subventricular Zone Neural Proliferation and Olfactory Bulb Neural Differentiation in MPTP-Induced Olfactory Dysfunction","authors":"Xianwen Zhang,&nbsp;Yafang Li,&nbsp;Xiongjie He,&nbsp;Ai Yang,&nbsp;Yali Chen,&nbsp;Fang Yan,&nbsp;Liping Bai,&nbsp;Jie Bai","doi":"10.1007/s11064-026-04850-3","DOIUrl":"10.1007/s11064-026-04850-3","url":null,"abstract":"<div><p>Despite hyposmia being a dominant non-motor manifestation of Parkinson’s disease (PD), its underlying driving mechanisms are poorly defined. The redox protein Thioredoxin-1 (Trx-1) offers neuroprotection against various insults; however, its potential involvement in the neural proliferation in the subventricular zone (SVZ) and neural differentiation in the olfactory bulb (OB) related to MPTP-induced olfactory dysfunction have not been previously established. Our research demonstrates that when Trx-1 is downregulated in the substantia nigra pars compacta (SNpc), MPTP-triggered olfactory deficits are significantly intensified. A key anatomical discovery in our study is the existence of projections from the SNpc to the SVZ. We established that the MPTP-driven death of SNpc dopaminergic (DAergic) neurons correlates with decreased dopamine D1 receptor (D1R) levels in the SVZ, an effect that is magnified by the loss of Trx-1. Alongside D1R reductions, MPTP suppressed a cascade of SVZ signaling molecules (phosphorylated PKA, Wnt3a, β-catenin, Pax6, cyclin D1, and CDK4), with Trx-1 deficiency causing even steeper declines. Furthermore, Trx-1 knockdown hindered the generation of immature neurons and disrupted DAergic neuronal differentiation within the OB. Collectively, our findings suggest that reduced Trx-1 expression in the SNpc may contribute to PD-related olfactory deficits, potentially via inhibiting SVZ neural proliferation, decreasing immature and mature neuron populations, and disrupted differentiation of OB immature neurons. By accelerating MPTP-triggered degeneration of DAergic neurons in the SNpc, Trx-1 downregulation reduces the SVZ of DAergic input. This disruption impairs D1R-mediated the neural proliferation in the SVZ, as well as the maturation and differentiation of immature neurons in OB, ultimately driving the progression of olfactory dysfunction in a PD mouse model.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628445","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":"Integrated In Vivo and In Vitro Analysis of Alpha-Synuclein Aggregation and Neuroinflammatory Amplification in a Composite Parkinson’s Disease Model","authors":"Xianfeng He,&nbsp;Huan Qi,&nbsp;Zhenwang Ma,&nbsp;Miao Lv,&nbsp;Songyan Gao,&nbsp;Cheng Mei,&nbsp;Jifang Yin","doi":"10.1007/s11064-026-04840-5","DOIUrl":"10.1007/s11064-026-04840-5","url":null,"abstract":"<div><p>This study aimed to investigate how α-synuclein (α-syn) is associated with microglial activation and inflammatory amplification in Parkinson’s disease (PD), particularly under pro-inflammatory conditions. In vitro, BV2 microglial cells were stimulated with α-syn preformed fibrils (PFFs) and lipopolysaccharide (LPS). In vivo, a composite PD mouse model was established using 6-OHDA, LPS, and SNCA-overexpressing adeno-associated virus (AAV). Inflammatory changes were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Midbrain transcriptomic profiles from model mice were analyzed using Affymetrix microarrays. Bioinformatic analyses included differential expression analysis with the limma package, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Transcriptomic analysis showed coordinated upregulation and strong positive correlations (<i>R</i> &gt; 0.73) among Snca, Tnfa, and Il1b in PD model mice. Enrichment analyses indicated prominent involvement of inflammation- and immune-related processes, including the JAK–STAT signaling pathway. In vitro, α-syn PFFs induced inflammatory responses in BV2 cells, and these responses were further enhanced by LPS co-stimulation. In vivo, the composite model showed increased α-syn aggregation, enhanced microglial activation, and elevated pro-inflammatory cytokine release under combined pathological conditions. Together, these findings indicate an amplified inflammatory response under combined pathological insults. Our findings suggest that α-syn aggregation is associated with enhanced microglial activation and inflammatory cytokine responses, and may exacerbate neuroinflammatory processes under inflammatory conditions in PD models.</p><h3>Graphical Abstract</h3><p>α-Syn exacerbates microglial pro-inflammatory skewing and promotes neuroinflammation in PD.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148615006","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":"Glycerol-3-Phosphate Attenuates Hypoxic-Ischemic Brain Injury via Modulation of Microglia-Mediated Neuroinflammation","authors":"Dani Qin,&nbsp;Yong Lei,&nbsp;Meini Le,&nbsp;Mengke Cheng,&nbsp;Yingmin Zhao,&nbsp;Lingyun Xia,&nbsp;Xinyuan Li,&nbsp;Xiaohua Dong","doi":"10.1007/s11064-026-04848-x","DOIUrl":"10.1007/s11064-026-04848-x","url":null,"abstract":"<div><p>Hypoxic-ischemic encephalopathy (HIE) is a severe perinatal brain injury that often leads to neurological impairments in survivors. Currently, effective therapeutic strategies for HIE remain limited and require further exploration. Emerging evidence indicates that microglia-mediated neuroinflammation plays a pivotal role in the pathophysiology of HIE. Nevertheless, clinically effective anti-inflammatory agents specifically targeting HIE are still lacking. Glycerol-3-phosphate (G3P) is a biologically significant metabolite involved in various cellular metabolic pathways. In this study, we investigated the neuroprotective effects of G3P against hypoxic-ischemic (HI)-induced brain injury by modulating microglial activation. In LPS-treated microglia, G3P suppressed the release of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, reduced reactive oxygen species (ROS) levels, restored mitochondrial membrane potential (MMP), and promoted a shift toward an anti-inflammatory microglial phenotype. In addition, G3P treatment in zebrafish showed no toxicity and significantly mitigated HI-induced oxidative stress, while suppressing both the recruitment and pro-inflammatory activation of mpeg1⁺ macrophages and lyzc⁺ neutrophils. Moreover, administration of G3P dramatically reduced infarct volume and alleviated neuronal loss in rats with hypoxic-ischemic brain damage (HIBD). Y-maze and Morris water maze tests demonstrated that G3P treatment significantly enhanced spatial learning and memory in HIBD rats. Furthermore, G3P markedly reduced the hyperactivation of microglia and astrocytes in both cortical and hippocampal regions. Mechanistically, Immunofluorescence and Western blot analyses revealed that G3P exerted anti-inflammatory effects by inhibiting cyclic GMP-AMP synthase -stimulator of interferon genes (cGAS-STING) signalling pathway and its downstream TBK1/the nuclear factor kappa B (NF-κB) signaling pathway. These findings highlight G3P as a promising therapeutic candidate for HIE.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590309","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":"Octreotide Attenuates Anxiety-Like Behaviors and Cognitive Deficits in a Rat Model of Post-traumatic Stress Disorder","authors":"Sina Motamedy,&nbsp;Gholam Hossein Meftahi","doi":"10.1007/s11064-026-04847-y","DOIUrl":"10.1007/s11064-026-04847-y","url":null,"abstract":"<div><p>Post-traumatic stress disorder (PTSD) is a long-lasting mental health condition characterized by persistent intrusive recollections, avoidance behaviors, mood and cognitive alterations, heightened arousal, and significant cognitive deficits, often accompanied by hypothalamic-pituitary-adrenal (HPA) axis dysregulation and neuroinflammation. This study evaluated the therapeutic potential of octreotide (OCT), a synthetic somatostatin analog, in a rat model of PTSD induced by foot-shock contextual fear conditioning. Male Wistar rats (<i>n</i> = 40) were randomly assigned to four groups (<i>n</i> = 10/group): Saline/No Stress (control), OCT/No Stress (drug alone), Saline/PTSD (model + saline), and OCT/PTSD (model + OCT). OCT was administered intraperitoneally at 50 µg/kg daily for 21 days post-induction. Behavioral outcomes were assessed using the Open Field Test (anxiety-like exploration and locomotor activity), Elevated Zero Maze (anxiety-like avoidance), and Morris Water Maze (spatial learning and memory). Plasma corticosterone concentrations were recorded on Days 0, 1, 7, 14, and 21. Hippocampal TNF-α, superoxide dismutase (SOD) activity, and malondialdehyde levels were quantified post-behavioral testing via ELISA. The Saline/PTSD group displayed significantly elevated plasma corticosterone (<i>P</i> &lt; 0.0001 from Day 1 onward), increased hippocampal TNF-α (<i>P</i> &lt; 0.0001), decreased SOD activity (<i>P</i> &lt; 0.0001), elevated MDA (<i>P</i> &lt; 0.0001), reduced locomotor activity and central exploration in the Open Field Test (<i>P</i> &lt; 0.0001 to <i>P</i> &lt; 0.01), and impaired spatial memory retention in the Morris Water Maze probe trial (<i>P</i> &lt; 0.0001). The Elevated Zero Maze did not reveal any significant differences. OCT treatment in the OCT/PTSD group significantly attenuated these alterations compared to the Saline/PTSD group, normalizing corticosterone from Day 7 onward, reducing TNF-α and MDA (<i>P</i> &lt; 0.0001), restoring SOD activity (<i>P</i> &lt; 0.01), and improving Open Field exploration and Morris Water Maze probe performance (<i>P</i> &lt; 0.01). These findings demonstrate that OCT is associated with neuroprotective, anti-inflammatory, and antioxidant effects in a PTSD model, attenuating HPA hyperactivity, neuroinflammation, oxidative stress, and behavioral/cognitive deficits (though direct SSTR-mediated mechanisms remain to be experimentally confirmed). Given its established safety profile and clinical approval for other indications, OCT represents a promising candidate for repurposing in PTSD treatment.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589521","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":"ApoTransferrin Induces Accumulation of Lipid Droplets in Oligodendroglial Cell","authors":"Estefanía Chamorro-Aguirre,&nbsp;Nicolás O. Favale,&nbsp;Lucila G. Pescio,&nbsp;María Julia Pérez,&nbsp;Jorge Correale,&nbsp;Juana Pasquini","doi":"10.1007/s11064-026-04825-4","DOIUrl":"10.1007/s11064-026-04825-4","url":null,"abstract":"<div><p>Transferrin is the principal iron-carrier protein and is primarily synthesized in the liver, oligodendrocytes (OLG), and choroid plexus. We previously demonstrated that apotransferrin (aTf) treatment induces OLG maturation in vitro and in vivo. Given that approximately 80% of myelin consists of lipids, predominantly cholesterol, tight regulation of lipid metabolism is essential during myelin formation. Lipid droplets (LDs) are dynamic intracellular organelles that store fatty acids as neutral lipids, including triglycerides and cholesterol esters. Recent studies have demonstrated the presence and regulated turnover of LDs in glial cells, suggesting roles in both physiological and pathological processes. During OLG maturation, the demand for lipid synthesis increases markedly to sustain membrane expansion and myelin production. Because this high lipid demand, we hypothesized that aTf-induced OLG maturation is associated with metabolic reprogramming involving lipid droplet dynamics, which may serve as a source of fatty acids for membrane biogenesis and energy production. In this context, LDs may represent a critical metabolic hub through which OLGs regulate lipid homeostasis and adapt to increased bioenergetic demands. However, the mechanisms governing LD biogenesis and turnover in oligodendroglial cells during development and under different metabolic conditions remain poorly understood. Importantly, LDs are now recognized as active participants in cellular metabolism, stress responses, and membrane biogenesis rather than passive lipid storage compartments. The aim of this study is to characterize LD dynamics, as well as specific lipid and protein profiles, in the Oli-Neu cell line and in oligodendroglial cells during the maturation process in the presence of aTf. We specifically investigate whether the aTf-induced increase in LD abundance reflects enhanced membrane biosynthetic requirements, with augmented energy production supported by β-oxidation of fatty acids released from triglycerides stored within LDs.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590147","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}