Brain Research最新文献

{"title":"Altered gut microbiome profiles in epileptic children are associated with spectrum of anti-seizure medication responsiveness.","authors":"Rattakarn Yuwattana, Kanokphong Suparan, Sasiwan Kerdphoo, Busarin Arunsak, Chinnuwat Sanguansermsri, Kamornwan Katanyuwong, Nipon Chattipakorn, Natrujee Wiwattanadittakul, Siriporn C Chattipakorn","doi":"10.1016/j.brainres.2024.149367","DOIUrl":"10.1016/j.brainres.2024.149367","url":null,"abstract":"<p><p>Gut microbiota plays a role in epilepsy. However, current knowledge of how gut dysbiosis is associated with a response to anti-seizure medications (ASMs) in epileptic children is still limited. We aimed to characterize the gut microbiota profiles in epileptic children based on response to ASMs. Eighty-six children aged 3-18 years old with a regular oral diet were enrolled onto the study and divided into three groups in accordance with ILAE definitions: 26 healthy controls, 31 drug-sensitive epilepsy (DSE) patients, and 29 drug-resistant epilepsy (DRE) patients. Based on ASM responsiveness, defined as a reduction in seizure frequency of at least 75 % over one year, DRE individuals were subclassified into 13 drug responsive (DRE-DR) and 16 drug non-responsive (DRE-DNR) patients. Feces were collected at the time of enrollment for gut microbiota analysis using 16S rRNA sequencing. Epileptic patients exhibited distinctive gut dysbiotic profiles. Differential abundance investigation revealed that CAG-56 was significantly increased in epileptic patients compared to controls. Saccharimonadales and Peptoclostridium significantly increased in the DSE group, compared to the DRE group. Vibrionaceae, especially Grimontia, Rhodobacteraceae, and Enterobacter were significantly abundant in the DRE-DNR group, followed by abundance in the DRE-DR and DSE groups. Outcomes from PICRUSt2 analysis predicted that epileptic patients, especially those in the DRE group, had increased metabolic pathways responsible for vanillin and taurine degradation, compared to controls. These findings suggest that gut dysbiosis could play roles in epileptogenesis and ASM resistance. Notably, the identified gut microbes could serve as predictive biomarkers for the DRE condition.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149367"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A non-purine inhibitor of xanthine oxidoreductase mitigates adenosine triphosphate degradation under hypoxic conditions in mouse brain.","authors":"Nana Sato, Teruo Kusano, Koji Nagata, Ken Okamoto","doi":"10.1016/j.brainres.2025.149444","DOIUrl":"10.1016/j.brainres.2025.149444","url":null,"abstract":"<p><p>The brain is an organ that consumes a substantial amount of oxygen, and a reduction in oxygen concentration can rapidly lead to significant and irreversible brain injury. The progression of brain injury during hypoxia involves the depletion of intracellular adenosine triphosphate (ATP) due to decreased oxidative phosphorylation in the inner mitochondrial membrane. Allopurinol is a purine analog inhibitor of xanthine oxidoreductase that protects against hypoxic/ischemic brain injury; however, its underlying mechanism of action remains unclear. In addition, febuxostat is a non-purine xanthine oxidoreductase inhibitor with a different inhibitory mechanism from allopurinol. The impact of febuxostat on brain injury has not been well investigated. Therefore, this study aimed to examine brain ATP and its catabolite levels in the presence or absence of allopurinol and febuxostat under hypoxic conditions by inactivating brain metabolism using focal microwave irradiation. The hypoxic treatment caused a decrease in the adenylate energy charge and ATP levels and an increase in its catabolic products in mouse brains. The febuxostat group showed higher energy charge and ATP levels and lower ATP catabolites than the control group. Notably, despite the comparable suppression of uric acid production in both inhibitor groups, allopurinol treatment was less effective than febuxostat. These results suggest that febuxostat effectively prevents hypoxia-induced ATP degradation in the brain and that its effect is more potent than allopurinol. This study will contribute to developing therapies for improving hypoxia-induced brain dysfunction.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149444"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of hyperglycemia on neuronal network function in an in vitro model of the ischemic penumbra.","authors":"C J B A Kersten, T H Vrielink, H M den Hertog, J Hofmeijer, J le Feber","doi":"10.1016/j.brainres.2024.149370","DOIUrl":"10.1016/j.brainres.2024.149370","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperglycemia is common in acute ischemic stroke, and associated with unfavorable outcome. However, the optimal glucose level is not known and cellular effects of hyperglycemia under hypoxia are largely unclear. We assessed how the extracellular glucose concentration affects cultured neuronal networks under experimental in vitro conditions, to provide a starting point for assessment of mechanisms at the neuronal network and cellular levels.</p><p><strong>Methods: </strong>We used in vitro cultured rat neuronal networks on micro-electrode arrays (MEAs) and glass coverslips. Twenty-four hours of controlled hypoxia was induced. We measured neuronal network activity during baseline (normoxia, 6 h), 24 h of hypoxia, and 6 h after reoxygenation, defined as the summed number of action potentials in 1 h bins. Apoptosis was determined intermittently with caspase 3/7 staining and microscopy. We compared groups of networks under glucose concentrations of 5.0 mmol/L, 7.0 mmol/L, 9.0 mmol/L, and 12.0 mmol/L.</p><p><strong>Results: </strong>Overall, during hypoxia, a gradual decrease in neuronal network activity and increase in apoptosis was found. There were faster decrease in activity (p < 0.01) and more apoptosis after 24 h of hypoxia under glucose levels of 12 mmol/L in a single-well MEA set-up (p < 0.05), and more apoptosis in glass coverslips with glucose levels of 12.0 mmol/L in comparison with 5 mmol/L (p = 0.03). These differences were not observed in multi-well MEAs, in which effects of hypoxia were much smaller than in single-well MEAs.</p><p><strong>Conclusion: </strong>Hyperglycemia was associated with a more rapid decrease of neuronal network activity during and more apoptosis after 24 h of hypoxia in cultured neuronal networks. Loss of neuronal activity and apoptosis probably play a role in poorer outcomes of stroke patients under hyperglycemia. Our model provides a starting point for further assessment of pathomechanisms.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149370"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of electroacupuncture on microglia phenotype and epigenetic modulation of C/EBPβ in SAMP8 mice.","authors":"Li Wang, Weixian Li, Wenhui Wu, Qing Liu, Min You, Xinyuan Liu, Cheng Ye, Jiangmin Chen, Qian Tan, Guangya Liu, Yanjun Du","doi":"10.1016/j.brainres.2024.149339","DOIUrl":"10.1016/j.brainres.2024.149339","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD), an age-progressive neurodegenerative disease, is featured by a relentless deterioration of cognitive abilities. In parallel with the hypotheses of Aβ and tau, microglia-mediated neuroinflammation is a core pathological hallmark of AD. Promoting the transition of microglia from M1 to M2 phenotype and inhibition of neuroinflammatory response provide new insights into the treatment of AD. And substantial studies have confirmed that overexpression of C/EBPβ accelerates the progression of AD pathology. Acupuncture is renowned for its unique advantages including safety and effectiveness, which has gained wide application in geriatric diseases, and thoroughly exploring the mechanism for its treatment of AD will provide scientific basis for its clinical application.</p><p><strong>Methods: </strong>In this study, SAMP8 mice were employed and EA therapy was performed as the main intervention. The combination of behavioural experiments (including water maze and novel objective recognition), Immunofluorescence, Western blot, and Chip-qPCR assay were performed to compare between different groups.</p><p><strong>Results: </strong>EA therapy facilitates the polarization of microglia from M1 to M2 phenotype, reduces pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) and promotes the expression of anti-inflammatory factors (IL-4 and IL-10), as well as attenuates neuroinflammation. Simultaneously, EA also inhibits the enrichment of H3K9ac at C/EBPβ promoter region and expression of C/EBPβ. Thus, it was evident that EA had a favorable effect on ameliorating cognitive decline in SAMP8 mice.</p><p><strong>Conclusion: </strong>EA therapy may ameliorate cognitive deficits in AD via facilitating microglia shift from M1 to M2 phenotype and epigenetically regulating C/EBPβ. And further studies are required to better understand how the mechanism between microglia and epigenetic modulation of C/EBPβ are effective in reversing AD.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149339"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPNMB attenuates neuroinflammation and improves ischemic stroke via modulation of PI3K/Akt and p38 MAPK signaling pathways.","authors":"Yukun Ping, Jiyu Li, Linlin Xie, Jie Zhao, Xuyu Chen, Danni Chen, Yamin Wang, Chao Jiang, Xiaobo Li","doi":"10.1016/j.brainres.2024.149381","DOIUrl":"10.1016/j.brainres.2024.149381","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a leading cause of disability and mortality worldwide, with limited effective treatments. Neuroinflammation plays a crucial role in the progression of ischemic brain injury. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has emerged as a potential regulator of inflammation, but its role and underlying mechanisms in ischemic stroke remain largely unknown.</p><p><strong>Methods: </strong>We investigated the expression profile, functional significance, and molecular pathways of GPNMB in ischemic stroke using a mouse model of middle cerebral artery occlusion (MCAO), transcriptome sequencing, and human serum samples. The effects of GPNMB knockdown on stroke outcomes, neuroinflammation, and neuronal damage were assessed in vivo. Bioinformatic analyses and experimental validation were performed to identify the downstream signaling pathways of GPNMB.</p><p><strong>Results: </strong>GPNMB was highly upregulated in the ischemic brain, with its expression peaking at 3-7 days post-MCAO. Serum GPNMB levels were elevated in ischemic stroke patients and correlated with stroke severity. GPNMB knockdown exacerbated stroke outcomes, neuroinflammation, and neuronal damage. Mechanistically, GPNMB positively modulated the PI3K/Akt/GSK3β pathway while negatively regulating p38 MAPK, JNK, and ERK activation. GPNMB knockdown enhanced the expression of NF-κB, a master transcriptional regulator of inflammation.</p><p><strong>Conclusion: </strong>GPNMB is highly upregulated in the ischemic brain and confers neuroprotection against ischemic injury by modulating neuroinflammation via the PI3K/Akt and p38 MAPK signaling pathways.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"149381"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-N-Butylphthalide alleviate Aβ-induced cellular senescence through the CDK2-pRB1-Caspase3 axis.","authors":"Yuanruhua Tian, Wenke Li, Yongbo Zhang","doi":"10.1016/j.brainres.2024.149435","DOIUrl":"10.1016/j.brainres.2024.149435","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) and leading to cellular senescence and cognitive deficits. Cellular senescence contributes significantly to the pathogenesis of AD through the senescence-associated secretory phenotype (SASP), exacerbating Aβ deposition. This study investigates the protective effects of 3-N-Butylphthalide (NBP), a compound derived from Apium graveolens Linn (Chinese celery), on Aβ-induced cellular senescence in U87 cells. Using RNA-sequencing and biochemical assays, we demonstrate that NBP ameliorate Aβ oligomer-induced cellular senescence and apoptosis, and regulated the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and components of the cyclin-dependent kinase 2 (CDK2)- phosphorylated retinoblastoma 1 (pRB1)-Caspase3 pathway. Moreover, NBP was shown to suppress the expression of SASP-related genes. These findings suggest that NBP rescues U87 cells from Aβ oligomer-induced senescence and apoptosis through modulating the CDK2-pRB1-Caspase3 axis and SASP expression. Our results underscore the potential of NBP as a senostatic agent for AD which have not been reported in previous studies, offering insights into its mechanisms of action and paving the way for future studies on its efficacy in vivo and in clinical settings. Thus, we contribute to growing evidence supporting the use of senolytic and senostatic agents in the treatment of AD.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149435"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The value of hippocampal sub-region imaging features for the diagnosis and severity grading of ASD in children.","authors":"Xiaofen Sun, Peng Zhang, Shitong Cheng, Xiaocheng Wang, Jingbo Deng, Yuefu Zhan, Jianqiang Chen","doi":"10.1016/j.brainres.2024.149369","DOIUrl":"10.1016/j.brainres.2024.149369","url":null,"abstract":"<p><strong>Background: </strong>Hippocampal structural changes in Autism Spectrum Disorder (ASD) are inconsistent. This study investigates hippocampal subregion changes in ASD patients to reveal intrinsic hippocampal anomalies.</p><p><strong>Methods: </strong>A retrospective study from Hainan Children's Hospital database (2020-2023) included ASD patients and matched controls. We classified ASD participants based on severity, dividing all subjects into four groups: normal, mild, moderate, and severe. High-resolution T1-weighted MRI images were analyzed for hippocampal subregion segmentation and volume calculations using Freesurfer. Texture features were extracted via the Gray-Level Co-occurrence Matrix. The Receiver Operating Characteristic curve was used to evaluate seven random forest predictive models constructed from volume, subregion, and texture features, as well as their combinations following feature selection.</p><p><strong>Results: </strong>The study included 114 ASD patients (98 boys, 2-8 years; 16 girls, 2-6 years; 17 mild, 57 moderate, 40 severe) and 111 healthy controls (HCs). No significant differences in volumes were found between ASD patients and HCs (adjusted P-value >0.05). The seven random forest models showed that single volume and texture features performed poorly for ASD classification; however, integrating various feature types improved AUC values. Further selection of texture, subregion, and volume features enhanced AUC performance across normal and varying severity categories, demonstrating the potential value of specific subregions and integrated features in ASD diagnosis.</p><p><strong>Conclusion: </strong>Random forest models revealed that hippocampal volume, texture features, and subregion characteristics are crucial for diagnosing and assessing the severity of ASD. Integrating selected texture and subregion features optimized diagnostic efficacy, while combining texture, subregion, and volume features further improved severity grading effectiveness.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149369"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural remodeling of the brain cortex and functional recovery following hypoglossal-facial neurorrhaphy in patients with facial paralysis.","authors":"Binbin Wang, Miao Ling, Chao Guo, Shengqiao Sun, Xingnan Zhang, Chenhao Hu, Hanjie Liu, Dezhi Li, Michael Schumacher, Binbin Sui, Song Liu","doi":"10.1016/j.brainres.2024.149437","DOIUrl":"10.1016/j.brainres.2024.149437","url":null,"abstract":"<p><strong>Objective: </strong>Peripheral nerve injury results in functional alterations of the corresponding active brain areas, which are closely related to functional recovery. Whether such functional plasticity induces relative anatomical structural changes remains to be investigated.</p><p><strong>Methods: </strong>In this study, we investigated the changes in brain cortical thickness in patients with facial paralysis following neurorrhaphy treatment at different follow-up times. Using magnetic resonance imaging (MRI) and the CAT12 toolbox, voxel-based whole-brain morphometric (VBM) analysis and region of interest (ROI) of cortical thickness estimation were performed in 11 patients with left facial paralysis before and after hypoglossal-facial nerve neurorrhaphy, and the results were compared to those of 20 healthy controls. All subjects were right-handed and had a left dominant hemisphere. Based on the ROIs, correlation analysis among the cortical structural changes, the House-Brackmann (H-B) grading scale and the compound muscle action potential (cMAP) amplitudes of the facial paralyzed/reinnervated muscles in the patients was conducted.</p><p><strong>Results: </strong>The results show dynamic changes in the thickness in the contralateral right cortex at corresponding functional areas in patients. The thickness of the ROIs was negatively correlated with the duration of facial paralysis from onset to neurorrhaphy but was positively correlated with the improvement in H-B grades and cMAP wave amplitudes recorded in the paralyzed/reinnervated facial muscles of patients. Interestingly, a significant increase in cortical thickness was observed in the ipsilateral left cortex of patients before surgery. However, the increased thickness of the left cortex was then gradually decreased and returned to the reference level of healthy controls following neurorrhaphy and reinnervation of paralyzed facial muscles.</p><p><strong>Conclusion: </strong>We concluded that dynamic changes in both sides of the brain cortex could reflect the state and effect of functional recovery in patients from the onset of facial paralysis before treatment to reinnervation and the return of lost function following neurorrhaphy, suggesting potential observation and treatment targets to predict prognosis and further promote functional recovery.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149437"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of Naringin on cognitive function, oxidative stress, cholinergic activity, CREB/BDNF signaling and hippocampal cell damage in offspring rats with utero-placental insufficiency-induced intrauterine growth restriction.","authors":"Samireh Nemati, Mohammad Amin Edalatmanesh, Mohsen Forouzanfar","doi":"10.1016/j.brainres.2025.149448","DOIUrl":"10.1016/j.brainres.2025.149448","url":null,"abstract":"<p><p>Intrauterine growth restriction (IUGR) induced by utero-placental insufficiency (UPI) results in delayed neural development and impaired brain growth. This study investigates the effects of Naringin (Nar) on memory, learning, cholinergic activity, oxidative stress markers, hippocampal CREB/BDNF signal pathway and cell damage in offspring of rats exposed to UPI. Twenty pregnant Wistar rats were randomly assigned to four groups: control, sham surgery, UPI + NS (UPI + normal saline as a vehicle), and UPI + Nar (UPI + Nar at 100 mg/kg/day). UPI was induced by permanently occluding the uterine anterior vessels on embryonic day (ED) 18. Naringin or saline was administered orally from ED15 to ED21. Behavioral assessments of offspring, including working memory, avoidance learning, and anxiety-like behavior, were conducted on a postnatal day (PND) 21. Subsequently, hippocampal acetylcholinesterase (AChE) activity, catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), hippocampal transcript level of cyclic AMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) and apoptotic neuron density in the hippocampus were evaluated. Naringin-treated rats demonstrated significant improvements in working and avoidance memory, increases in CAT, SOD, and TAC, CREB, BDNF and reductions in AChE activity, MDA levels, apoptotic neuron density, and anxiety-like behaviors compared to the UPI + NS group (p < 0.05). Naringin mitigates hippocampal cell damage, cognitive impairments, and anxiety by enhancing antioxidant defenses, modulating cholinergic activity and CREB/BDNF signaling in the brains of UPI-exposed offspring.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"149448"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of delta opioid receptor inhibition of parallel fibers-purkinje cell synaptic transmission in the mouse cerebellar cortex.","authors":"Lu Zhang, Dan Wang, Shuang Shi, Shuang Wu, Zhi Li, Jun Nan, Yan Lan","doi":"10.1016/j.brainres.2024.149374","DOIUrl":"10.1016/j.brainres.2024.149374","url":null,"abstract":"<p><p>Delta opioid receptors (DORs) are widely expressed throughout the central nervous system, including the cerebellum, where they play a regulatory role in neurogenesis. In the cerebellar cortex, Purkinje cells (PCs), the sole output neurons, receive glutamatergic synaptic input from parallel fibers (PFs)-the axonal extensions of granule cells-forming PF-PC synapses. However, the precise distribution of DORs within these synapses and their impact on synaptic transmission remain unclear. In this study, we utilized whole-cell patch-clamp recordings and neuropharmacological approaches to explore the effects of DORs activation on PF-PC synaptic transmission in the mouse cerebellar cortex and to elucidate the underlying mechanisms. We found that the selective DORs agonist DPDPE significantly reduced the amplitude and area under the curve (AUC) of PF-PC evoked excitatory postsynaptic currents (eEPSCs), accompanied by an increase in the paired-pulse ratio (PPR). This inhibitory effect was blocked by the DORs antagonist Naltrindole. Additionally, DPDPE decreased the frequency of PF-PC miniature excitatory postsynaptic currents (mEPSCs) without affecting their amplitude, indicating a presynaptic site of action. When the protein kinase A (PKA) inhibitor PKI was added to the internal solution of the recording electrode, it did not alter the DPDPE-induced suppression of PF-PC mEPSC frequency. However, this suppression was reversed by KT5720, a cell-permeable PKA-specific inhibitor. These findings suggest that DPDPE inhibits PF-PC synaptic transmission through the preferential activation of presynaptic DORs, with this process being dependent on the cyclic adenosine monophosphate (cAMP)-PKA signaling pathway.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149374"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}