Neurochemical Research最新文献

{"title":"Consumption of Fructose by Cultured Primary Rat Astrocytes","authors":"Mariana Mesa-Leal,&nbsp;Ralf Dringen","doi":"10.1007/s11064-026-04873-w","DOIUrl":"10.1007/s11064-026-04873-w","url":null,"abstract":"<div><p>Fructose has recently gained substantial interest in the context of diseases that are connected with sucrose-rich diets. Several studies have shown that astrocytes are able to metabolize fructose to some extent but less efficiently than glucose. To study whether and how fructose can fuel astrocytic energy metabolism, we used cultured primary astrocytes as model. These cells consumed fructose in a time- and concentration-dependent manner that followed apparent Michaelis-Menten type kinetics with a K_M value of 2.8 ± 0.9 mM and a V_Max value of 325 ± 32 nmol/(mg × h). Although the specific consumption of glucose and the production of lactate from glucose were around 4 times higher than the respective values for fructose, the loss of astrocytic cellular ATP during starvation was prevented by both fructose and glucose with similar concentration dependencies. However, severe differences were observed for fructose- and glucose-fed astrocytes, if the mitochondrial oxidative phosphorylation was impaired. For fructose-treated astrocytes the application of inhibitors of mitochondrial ATP regeneration almost doubled the low basal glycolytic lactate production, but this was insufficient to prevent a rapid and severe loss in cellular ATP content and subsequent cell toxicity. In contrast, for glucose-treated cells a strong upregulation of glycolysis was connected with a slow ATP loss and a delayed onset of toxicity. Although hexokinase in astrocytic cell lysates was found to have a high K_M value for fructose (4.4 ± 1.1 mM), hardly any free fructose was found in astrocytic lysates even after exposure to 10 mM fructose, suggesting that not the phosphorylation but rather the uptake of fructose limits astrocytic fructose consumption. The data presented demonstrate that millimolar concentrations of fructose are required to make this hexose a suitable extracellular substrate for astrocytic metabolism and that fructose metabolism provides energy mainly by mitochondrial respiration.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-026-04873-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148837989","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":"Prednisone Exposure During Pregnancy Increases Susceptibility to Epilepsy in Adult Offspring Mice","authors":"Xue-Lei Cheng,&nbsp;Meng-Liu Zeng,&nbsp;Ting-Ting Wang,&nbsp;Shuai Zhang,&nbsp;Ming-Cui Luo,&nbsp;Xin-Li Zhou,&nbsp;Li-Yi Wei,&nbsp;Hui Wang,&nbsp;Dan Xu,&nbsp;Bi-Wen Peng","doi":"10.1007/s11064-026-04869-6","DOIUrl":"10.1007/s11064-026-04869-6","url":null,"abstract":"<div><p>Prenatal glucocorticoid exposure is associated with multiple long-term health risks in offspring. Prednisone is the most commonly used oral glucocorticoid. Although prior studies have shown that prenatal prednisone exposure (PPE) induces renal abnormalities in offspring rats and genital developmental abnormalities in offspring mice, its effects on brain development remain poorly understood. Our results showed that PPE impairs the proliferation and differentiation of neural progenitor cell, reduces neurogenesis, induces synaptic dysfunction, and affects microglial proliferation in offspring mice. These impairments were observed in female offspring during gestational days 0 to 9 (GD0-9) and GD0-18, whereas in male offspring, they were observed during GD0-18. We further identified that transient receptor potential vanilloid 1 (TRPV1) is upregulated in PPE offspring mice, and the epileptic phenotype was significantly attenuated in TRPV1^−/− mice. Mechanistically, this attenuation was mediated by glucocorticoid receptor activation, which subsequently triggered intracellular cyclic adenosine monophosphate (cAMP) signaling. Collectively, our study identifies a specific time window of neurotoxicity associated with PPE and provides evidence supporting the developmental origin of epilepsy in this context.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p>PPE impairs the proliferation of neural precursor cells, the development of neurons, and enhances microglial proliferation via the GR/cAMP-TRPV1 signaling pathway in offspring mice, thereby increasing the epilepsy susceptibility of offspring mice</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148837981","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":"The Potential of Cannabidiol for the Treatment of Psychosis: Endocannabinoid Regulation of Serotonergic Neurotransmission via Serotonin 5-HT1A/2A Receptors","authors":"Kazutoshi Yonemura,&nbsp;Nobue Kitanaka,&nbsp;Kazuo Tomita,&nbsp;F. Scott Hall,&nbsp;Moe Matsuo,&nbsp;Kento Igarashi,&nbsp;Tomoaki Sato,&nbsp;George R. Uhl,&nbsp;Junichi Kitanaka","doi":"10.1007/s11064-026-04860-1","DOIUrl":"10.1007/s11064-026-04860-1","url":null,"abstract":"<div><p>Cannabis, widely used for both medical and non-medical purposes, primarily contains Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD). Δ⁹-THC is the main driver of cannabis abuse and of psychological and physical dependence, whereas CBD has limited abuse potential and is even being investigated as a treatment for cannabis use disorder and other conditions. This review aims to clarify how the molecular and receptor-level mechanisms of CBD, compared with Δ⁹-THC, shape its distinct therapeutic profile and low liability for addiction, thereby informing the safer clinical application of CBD-containing interventions to schizophrenia. CBD exerts sedative and therapeutic effects, including in treatment-resistant epilepsy, and acts in part via CB1 and CB2 receptors that also mediate Δ⁹-THC actions. While Δ⁹-THC activates these receptors as an agonist, triggering Gi-coupled signaling cascades such as MAPK pathways and suppressing presynaptic monoamine release, CBD functions as a non-competitive negative allosteric CB1 modulator and non-competitive antagonist of Δ⁹-THC. These distinct intracellular signaling mechanisms are considered to underlie the markedly different pharmacological profiles and abuse liabilities of Δ⁹-THC and CBD. CBD also engages multiple CNS targets beyond CB1 and CB2, including GPR55, TRPV1 and ENT1, which are implicated in anticonvulsant, anti-inflammatory, analgesic and neuroprotective actions. Although GPR55 pharmacology remains controversial and Δ⁹-THC shows inconsistent activity at this receptor, converging evidence indicates that CBD can antagonize CB1/CB2 and modulate atypical cannabinoid-sensitive proteins. Excessive activation of certain serotonin receptors, including 5-HT_1A/2A, are thought to underlie some symptoms of psychosis. These diverse molecular actions are thought to underlie CBD’s broad therapeutic potential across seizures and other CNS disorders, providing a mechanistic rationale for exploring CBD as a treatment option for psychosis in schizophrenia and stimulant-induced psychotic states.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148837982","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":"Retraction Note: Inhibition of c-Jun N-terminal Kinase Ameliorates Early Brain Injury After Subarachnoid Hemorrhage Through Inhibition of a Nur77 Dependent Apoptosis Pathway","authors":"Yuxiang Dai,&nbsp;Wen Zhang,&nbsp;Xiaoming Zhou,&nbsp;Jixin Shi","doi":"10.1007/s11064-026-04877-6","DOIUrl":"10.1007/s11064-026-04877-6","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838061","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":"Formononetin Attenuates Seizure Severity and Cognitive Deficits in PTZ-Kindled Rats with Associated Changes in Oxidative Stress and P2 X 7/IL-1β/Glutamate Signalling Markers","authors":"Harsh Yadav,&nbsp;Baban Thawkar,&nbsp;Nisarg Sawant","doi":"10.1007/s11064-026-04849-w","DOIUrl":"10.1007/s11064-026-04849-w","url":null,"abstract":"<div><p>Epilepsy is a chronic neurological disorder characterised not only by recurrent seizures but also by cognitive decline, neuroinflammatory responses, and oxidative stress, implicating the ATP-gated P2 X 7 receptor and downstream inflammasome signalling in epileptogenesis. Utilising the pentylenetetrazol (PTZ)-induced kindling model in rats, this research aimed to evaluate the neuroprotective and seizure-attenuating potential of the natural isoflavone Formononetin (FMNT), with emphasis on cognitive outcomes. Chronic epilepsy was induced in Groups II to V by repeated intraperitoneal administration of PTZ (40 mg/kg), while FMNT (20 and 40 mg/kg, p.o.) and sodium valproate (300 mg/kg, p.o.) were concurrently administered to the respective treatment groups. Group I received saline and served as vehicle control. Seizure parameters were assessed using the modified Racine scale. Cognition was evaluated using the Morris Water Maze (MWM) and Novel Object Recognition Test (NORT). Oxidative stress markers, neuroinflammatory mediators, and glutamate levels were quantified biochemically. Histopathological evaluation was conducted using Nissl staining, and molecular docking explored interactions between FMNT and neuroinflammatory targets. FMNT treatment produced a significant reduction in seizure severity and frequency, prolonged seizure latency, and improvements in spatial and recognition memory deficits. Additionally, FMNT increased antioxidant defences, reduced lipid peroxidation, and markedly reduced IL-1β, P2 X 7, and glutamate levels. Histological analysis confirmed preservation of neuronal architecture, while docking studies demonstrated favourable binding of FMNT with P2 X 7, NLRP3, TLR4, and caspase-1. These findings suggest that FMNT attenuates PTZ-kindling-associated seizure severity and cognitive deficits, potentially through antioxidant effects and suppression of P2 X 7/IL-1β/glutamate-associated inflammatory signalling. Further target-specific mechanistic studies are warranted.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838125","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":"FoxO3a-Smad4 Co-localization and Autophagy Alterations are Associated with Cognitive Impairment in Alcohol-Dependent Rats Fed a High-Fat Diet","authors":"Shuping He,&nbsp;Yuhang Ren,&nbsp;Qingmei Jiang,&nbsp;Yutong Dong,&nbsp;Fangyi Li,&nbsp;Jikai Ren,&nbsp;Qian Song,&nbsp;Jiahui Zhao,&nbsp;Changhao Yin,&nbsp;Weina Zhao","doi":"10.1007/s11064-026-04856-x","DOIUrl":"10.1007/s11064-026-04856-x","url":null,"abstract":"<div><p>To investigate the effects of alcohol dependence (with high-fat) on the morphology and structure of rat hippocampal cells as well as learning and memory abilities, and to explore the role played by FoxO3a-Smad4-regulated autophagy. The hippocampal neurons and synaptic ultrastructure were observed by using eosin-s hematoxylin staining and transmission electron microscopy, the expression levels of hippocampal FoxO3a, Smad4 and autophagy proteins were detected by Western blotting, and the co-localisation of FoxO3a and Smad4 was observed by laser confocal. Alcohol dependence was associated with the development of cognitive impairment, resulting in pathological changes in hippocampal neurons and altered synaptic plasticity in cognition-related brain regions, while alcohol + high-fat increased the risk of cognitive impairment, with the increase of ingested alcohol concentration and the increase of high-fat dietary intake, the rats’ learning and memory abilities were significantly reduced. The present findings suggest that alcohol dependence combined with a high-fat diet is associated with cognitive impairment, hippocampal neuronal and synaptic damage, and alterations in FoxO3a-Smad4 expression and autophagy markers in rats. These changes potentially involving the TGF-β1/FoxO3a-Smad signalling axis and associated alterations in autophagy markers. Further causal studies are warranted to determine the precise functional contribution of this axis.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-026-04856-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823597","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":"Cellular Prion Protein as a Novel Regulator of Vascular Plexus Stability During Retinal Angiogenesis","authors":"Bárbara Gomes da Rosa,&nbsp;Felipe Leser,&nbsp;Marco Aurélio Alves,&nbsp;Eliel de Souza Leite,&nbsp;Celina Garcia,&nbsp;Luiz Henrique Medeiros Geraldo,&nbsp;Rackele Ferreira do Amaral,&nbsp;Catarina Freitas,&nbsp;Flavia Regina Souza Lima","doi":"10.1007/s11064-026-04867-8","DOIUrl":"10.1007/s11064-026-04867-8","url":null,"abstract":"<div><p>Angiogenesis is essential not only during embryogenesis but also in adult physiology and disease, relying on vascular endothelial growth factor (VEGF) gradients to guide tip cell sprouting. Cellular prion protein (PrP^C), expressed in several neurovascular unit (NVU) cell types, regulates neuronal and astrocytic differentiation through laminin binding, yet its role in angiogenesis remains understudied. Here, we investigated its function in retinal vascular development. In PrP^C knockout mice, the superficial retinal plexus exhibited increased tip cell density and branching, accompanied by microglial morphofunctional alterations and reduced <i>Vegf-c</i> expression, features consistent with impaired vascular stability. Conditioned media from PrP^C knockout microglia was sufficient to increase endothelial instability in vitro, indicating that altered microglial signalling can modulate vascular phenotype. Moreover, Laminin 411 / 511 isoforms and Collagen IV showed decreased expression in the retinal vascular basement membrane, supporting altered basement membrane composition. At later developmental stages, absence of PrP^C led to increased vertical sprouting into deeper retinal layers, resulting in transient hypervascularization of the deep plexus and defective laminin deposition across all vascular layers. These changes were accompanied by altered ZO-1 distribution and disrupted retinal layer organization, as indicated by reduced inter-plexus distance. Collectively, our findings identify PrP^C as regulator of sprouting angiogenesis and vascular stabilization in the developing retina. The data support a model in which PrP^C modulates neurovascular interactions, through both microglia-dependent and endothelial-intrinsic mechanisms, although the relative contribution of these components remains to be determined.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-026-04867-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823586","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":"Metabolomics and Proteomics Analyses Reveal the Protective Effect of Crocetin Against Depressive-Like Behaviors Mice","authors":"Susu Lin,&nbsp;Ziwei Chen,&nbsp;Qinghe Zhou,&nbsp;Mingxin Dong,&nbsp;Wenyu Sun","doi":"10.1007/s11064-026-04871-y","DOIUrl":"10.1007/s11064-026-04871-y","url":null,"abstract":"<div><p>Depression is a common neuropsychiatric disorder, and our previous study revealed that crocetin has antidepressant effects, while the antidepressant mechanism of crocetin is still unknown. This study aimed to probe the antidepressant mechanism of crocetin in chronic unpredictable mild stress (CUMS) induced depressive-like behaviors mice. The hippocampus was collected for metabolomic analyses using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The ileum was collected for proteomics analyses.The results revealed that crocetin treatment could significantly improve CUMS-induced depression. Metabolic showed that crocetin-treated suggestively altered the metabolite levels in the hippocampus of depressive-like mice. In total, 92 nominal differential abundant metabolites including 37 nominally upregulated and 55 nominally downregulated metabolites, were observed between CUMS and crocetin-treated groups. These differential metabolites were suggestively enriched in the pathway of glycerophospholipid metabolism and oxidative phosphorylation. Crocetin also significantly altered protein synthesized in the ileum of depressive-like behaviors mice. In total, 419 proteins were differentially regulated, including 231 nominally upregulated and 188 nominally downregulated proteins. These differential proteins were significantly enriched in the pathway of retinol metabolism and steroid hormone biosynthesis, and suggestively enriched in the pathway of inflammation-mediated transient receptor potential (TRP) channel, arachidonic acid metabolism, linoleic acid metabolism, and serotonergic synapse. Based on omics analysis, we have formulated a hypothesis for further verification: crocetin significantly affect the lipid metabolism due to its anti-inflammatory and antioxidant activities, especially glycerophospholipid metabolism in the body, thereby exerting an antidepressant effect. These effects may be closely related to the regulatory role of crocetin in the inflammatory state of the ileum. This study demonstrates that multi-omics analysis can provide new insights into the mechanism of drug antidepressant effects.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817159","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":"Glutamatergic Projection from the Ventrolateral Periaqueductal Gray to the Parafascicular Nucleus of the Thalamus Contributes to the Modulation of Neuropathic Pain in Mice","authors":"Dong-Ning Li,&nbsp;Yao-Hua Liu,&nbsp;Jia Li,&nbsp;Hui-Min Tian,&nbsp;Li-Ming Liu,&nbsp;Zi-Ang Li,&nbsp;Zhong-Yi Liu,&nbsp;Sha-Sha Tao,&nbsp;Jin Cheng,&nbsp;Tian-Yu Zhao,&nbsp;Yu-Jing Chen,&nbsp;Jia-Qi Zhu,&nbsp;Fen-Sheng Huang,&nbsp;Liang Li,&nbsp;Fei Li,&nbsp;Yun-Qing Li","doi":"10.1007/s11064-026-04870-z","DOIUrl":"10.1007/s11064-026-04870-z","url":null,"abstract":"<div><p>Chronic pain is frequently accompanied by increased pain sensitivity and affective disturbances. The ventrolateral periaqueductal gray (vlPAG) and the parafascicular nucleus of the thalamus (PF) are key nodes in pain modulation. However, the functional role of the vlPAG-PF neural pathway remains poorly understood. In this study, we employed an integrative approach combining neuroanatomical tracing and chemogenetic techniques to investigate the role of the vlPAG^vGluT2-PF neural pathway in pain modulation. Our results demonstrate that vGluT2-positive neurons in the vlPAG project to the PF. Chemogenetic inhibition of the vlPAG^vGluT2-PF pathway increased mechanical sensitivity in naïve mice, whereas activation of this pathway alleviated mechanical hypersensitivity in mice subjected to spared nerve injury (SNI). These results demonstrate that the vlPAG^vGluT2-PF pathway is involved in the modulation of neuropathic pain and provide experimental evidence for further investigation of this pathway.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817134","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":"Acute Ethanol Exposure Inhibits GABA Uptake in Embryonic Chicken Retina","authors":"A. C. O. Damascena,&nbsp;A. K. Abramov,&nbsp;L. Pinheiro,&nbsp;M. Dos Santos Pereira,&nbsp;P. Trindade,&nbsp;J. Stipursky,&nbsp;R. A. De Melo Reis,&nbsp;R. C. C. Kubrusly","doi":"10.1007/s11064-026-04868-7","DOIUrl":"10.1007/s11064-026-04868-7","url":null,"abstract":"<div><p>GABA is the major inhibitory amino acid in the central nervous system (CNS), and its homeostasis is crucial for inhibitory/excitatory balance. Its reuptake is mediated by GABA transporters, including type 1 (GAT-1), a high-affinity GABA plasma membrane transporter. Ethanol (EtOH) consumption enhances GABA inhibitory effects; however, the impact of acute EtOH exposure on GABAergic function during development remains to be understood. Therefore, we aimed to evaluate whether acute EtOH exposure modulates GABA transport in chicken retina, a well-established model for investigating neurochemical studies. GABA transporter is functional from the onset of synaptogenesis (embryonic day—E11) to E16 in chicken retina. A dose–response curve in E11 suggested that exposure to 0.1% EtOH reduced GABA uptake. This effect was not related to cell death, as cytotoxicity assays performed through lactate dehydrogenase (LDH) release showed no significant changes in E11. Additionally, inhibition of PKA and PKC pathways reversed the EtOH 0.1%-effect, suggesting the involvement of these kinases in regulating GABA transport. In contrast, Ifenprodil treatment did not alter the inhibitory effect of EtOH on GABA uptake, suggesting that GluN2B-containing NMDA receptors are not major contributors to this response. Our findings demonstrate that GABA uptake through GAT-1 during synaptogenesis may play a role in the synaptic circuitry of avian retina. Acute exposure to 0.1% EtOH did not significantly alter GABA uptake at E16 as was indicated in E11, suggesting an age-dependent effect of EtOH on retinal development, independent of cell death. These results support the hypothesis that acute EtOH exposure modulates GABA transport during retinal development, with the involvement of PKA and PKC pathways in this response.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-026-04868-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783419","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}