Neuroreport最新文献_第4页

Impaired synaptic transmission and long-term potentiation in severe combined immunodeficient (SCID) mice. 严重联合免疫缺陷（SCID）小鼠突触传递和长期增强功能受损。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-04-02 Epub Date: 2025-03-26 DOI: 10.1097/WNR.0000000000002149

Leonardo Lupacchini, Cristiana Mollinari, Virginia Tancredi, Enrico Garaci, Daniela Merlo

{"title":"Impaired synaptic transmission and long-term potentiation in severe combined immunodeficient (SCID) mice.","authors":"Leonardo Lupacchini, Cristiana Mollinari, Virginia Tancredi, Enrico Garaci, Daniela Merlo","doi":"10.1097/WNR.0000000000002149","DOIUrl":"10.1097/WNR.0000000000002149","url":null,"abstract":"DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is one of the key enzymes involved in DNA double-strand break (DSB) repair. However, recent studies using DNA-PKcs knockout mice revealed that DNA-PKcs plays an important role in neuronal plasticity. The aim of this study was to examine the role of DNA-PKcs on synaptic plasticity in severe combined immunodeficiency disease (SCID) mice that carry a mutation resulting in a DNA-PKcs protein devoid of kinase activity but still expressed in cells, although with a small COOH-terminal truncation. To this aim, we carried out electrophysiological and molecular analysis on hippocampal slices from wild-type (WT) and SCID mice. Electrophysiological analysis showed an impairment in the basal synaptic transmission in SCID mice compared with WT, whereas paired-pulse facilitation, caused by presynaptic mechanisms, was not different in the two groups of animals. By contrast, tetanic stimulation induced long-term potentiation (LTP) with values that were approximately 43% lower in slices from SCID mice compared with WT. The same slices used for electrophysiology were analyzed to study the phosphorylation state of cAMP response element-binding protein (CREB) and extracellular signal-regulated kinases and to evaluate mRNA expression levels of CREB-target genes at different times after LTP induction. In conclusion, molecular analysis did not show significant differences between SCID and WT brain slices, thus confirming the evidence that DNA-PKcs kinase activity directly regulates neuronal functions and plays a novel role beyond DSB repair. Moreover, these results indicate that studies using SCID mice involving analysis of synaptic function need to be interpreted with caution.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"36 6","pages":"290-296"},"PeriodicalIF":1.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia-preconditioned human dental pulp stem cells transplantation alleviates hypoxic-ischemic brain damage via STAT3/NLRP3/Caspase-1 axis in neonatal rats. 缺氧预处理人牙髓干细胞移植通过STAT3/NLRP3/Caspase-1轴减轻新生大鼠缺氧缺血性脑损伤。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-19 Epub Date: 2025-02-26 DOI: 10.1097/WNR.0000000000002144

Xiangyan Fang, Shujun Gao, Yan Li, Kang Xu, Qixiao Huo, Peilun Xiao, Xiaoli Wang, Fantao Wang

{"title":"Hypoxia-preconditioned human dental pulp stem cells transplantation alleviates hypoxic-ischemic brain damage via STAT3/NLRP3/Caspase-1 axis in neonatal rats.","authors":"Xiangyan Fang, Shujun Gao, Yan Li, Kang Xu, Qixiao Huo, Peilun Xiao, Xiaoli Wang, Fantao Wang","doi":"10.1097/WNR.0000000000002144","DOIUrl":"10.1097/WNR.0000000000002144","url":null,"abstract":"This study was conducted to examine the effects and mechanisms of hypoxia-preconditioned human dental pulp stem cells (H-hDPSCs) transplantation on microglial pyroptosis in neonatal rats with hypoxic-ischemic brain damage (HIBD). The hDPSCs were extracted using the tissue block method and identified by immunofluorescence staining. The HIBD model was constructed using the classical Rice-Vannucci method. 24 h after HIBD, normoxic preconditioning hDPSCs (N-hDPSCs) and H-hDPSCs were transplanted into the lateral ventricle. The brain damage was examined by hematoxylin & eosin and Nissl stainings 72 h after transplantation. The expression of signal transducer and activator of transcription 3 (STAT3)/NOD-like receptor family pyrin domain-containing 3 (NLRP3)/Caspase-1 axis-related proteins was analyzed by immunofluorescence staining and western blots. Tissue levels of interleukin-1 beta (IL-1β) were derived from ELISA. After modeling, the neural cells in the HIBD group were disordered and sparsely scattered, with a deficiency of nitrosamines. The data revealed that the phosphorylated STAT3, NLRP3, Cleaved-Caspase 1, N-terminal fragment of gasdermin D (GSDMD-N), and IL-1β protein expression were significantly lower in the H-hDPSCs and N-hDPSCs groups compared to the HIBD group. The protein expression in the H-hDPSCs group was considerably lower than in the N-hDPSCs group. H-hDPSCs may protect microglia from pyroptosis by regulating the STAT3/NLRP3/Caspase-1/GSDMD axis to alleviate inflammatory damage, and attenuate HIBD in newborn rats at the same time. Moreover, the therapeutic effect of H-hDPSCs transplantation was superior to that of N-hDPSCs transplantation.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"247-256"},"PeriodicalIF":1.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458782","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}

引用次数: 0

Asexual versus sexual women: a test-retest study on differences in brain activity. 无性女性与有性女性：一项关于大脑活动差异的复测研究。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-19 Epub Date: 2025-02-26 DOI: 10.1097/WNR.0000000000002147

Hannes Nessling, Laura Mathis, Guilherme Wood, Karl Koschutnig, Jan Willem Koten

{"title":"Asexual versus sexual women: a test-retest study on differences in brain activity.","authors":"Hannes Nessling, Laura Mathis, Guilherme Wood, Karl Koschutnig, Jan Willem Koten","doi":"10.1097/WNR.0000000000002147","DOIUrl":"10.1097/WNR.0000000000002147","url":null,"abstract":"Asexuality has a prevalence of approximately 1% in the population and should not be confused with hypoactive sexual desire disorder as defined in the DSM-5. Asexuality is characterized by minimal to no sexual attraction to others. The neural correlates of asexuality remain largely unknown, and the test-retest reliability of sexually induced brain activity is still elusive. In this functional MRI study, we used the Asexual Identification Scale to identify 14 asexual women (mean score ~ 46) and 21 sexual women (mean score ~ 14). We modeled brain activity in response to sexual stimuli using the canonical hemodynamic response function and performed voxel-wise test-retest reliability analysis on contrast weight maps. Additionally, we applied pattern recognition methods to distinguish asexual from sexual women. The voxel-wise test-retest reliability of brain activity in response to sexual stimuli was remarkably robust for sexuality relevant brain areas [mean ICC(2,1) = 0.66]. The conjunction analysis comparing sexual stimuli to baseline showed that group brain activity was reproducible at a Bonferroni-corrected P value of 1.78e -6 . The direct contrast between asexual and sexual women yielded no significant differences at the single-voxel level. A support vector machine, however, identified 71% ( P < 0.03) of asexual and sexual women correctly when test and retest runs were combined. In conclusion, although our sample size is small, our findings suggest that differences between asexual and sexual women may have their neural roots in subtle variations in brain activity across extensive brain regions, which might be identified using classification methods.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"272-278"},"PeriodicalIF":1.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458774","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}

引用次数: 0

Electroacupuncture regulates FTO/Nrf2/NLRP3 axis-mediated pyroptosis in cerebral ischemia-reperfusion injury. 电针调节脑缺血再灌注损伤中FTO/Nrf2/NLRP3轴介导的焦亡。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-19 Epub Date: 2025-02-26 DOI: 10.1097/WNR.0000000000002146

Chenglong Li, Haisheng Ji, Wei Mao, Lida Zhang, Tingting Tong, Junli Wang, Liyuan Cai, Hai Wang, Tingting Sun, Hu Yi, Shijun Li, Ying Tu, Junyu Zhang, Haitao Wang, Haiyang Wu, Wei Han, Ying Wang

{"title":"Electroacupuncture regulates FTO/Nrf2/NLRP3 axis-mediated pyroptosis in cerebral ischemia-reperfusion injury.","authors":"Chenglong Li, Haisheng Ji, Wei Mao, Lida Zhang, Tingting Tong, Junli Wang, Liyuan Cai, Hai Wang, Tingting Sun, Hu Yi, Shijun Li, Ying Tu, Junyu Zhang, Haitao Wang, Haiyang Wu, Wei Han, Ying Wang","doi":"10.1097/WNR.0000000000002146","DOIUrl":"10.1097/WNR.0000000000002146","url":null,"abstract":"Electroacupuncture (EA) demonstrates neuroprotective in cerebral ischemia-reperfusion (I/R) injury. N6-methyladenosine (m6A) is found to contribute to the pathogenesis of neurological conditions recently. The objective of this study is to investigate the effects of EA on m6A and related mechanism in cerebral I/R injury. After the middle cerebral artery occlusion/reperfusion (MCAO/R) operation was used to establish rat models with cerebral I/R injury, EA was applied to Baihui (GV20) and Dazhui (GV14) once daily for 7 consecutive days. Subsequently, the modified Neurological Severity Score, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin and eosin staining were performed to assess the neurological damage. To investigate the potential target, the total RNA m6A level and relevant regulators (METTL3, METTL14, WTAP, FTO, and ALKBH5) were examined. In the next step, FTO, Nrf2, NLRP3, IL-18, IL-1β, and TUNEL-positive rates were detected, while the shRNA-FTO was administered to suppress FTO expression. EA improved neurobehavioral disorders, infarct volume, and pathological damage induced by cerebral I/R injury. Mechanically, EA reduced the total RNA m6A level by selectively regulating FTO, but not METTL3, METTL14, WTAP, and ALKBH5. Furthermore, EA could enhance Nrf2 and suppress NLRP3, IL-18, IL-1β, and TUNEL-positive rates, which was reversed by the shRNA-FTO injection. Our findings indicate that EA may alleviate FTO/Nrf2/NLRP3 axis-mediated pyroptosis in cerebral I/R injury, providing a more unified understanding of the neuroprotective effects of EA. Specifically, EA intervention appears to promote the expression of FTO, leading to a reduction of m6A level, which activates Nrf2 and subsequently suppresses NLRP3-mediated pyroptosis.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"257-266"},"PeriodicalIF":1.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458779","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}

引用次数: 0

State-dependent neural signatures of autistic traits: evidence from fNIRS-based fractional amplitude of low-frequency fluctuation analysis during natural social interaction. 自闭症特征的状态依赖神经特征：来自自然社会互动中基于fnir的低频波动分数幅值分析的证据。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-19 Epub Date: 2025-02-26 DOI: 10.1097/WNR.0000000000002145

Shuyuan Feng, Yuqing Yuan, Mingliang Wang, Jianing Zhang, Lin Ding, Peng Zhang, Xuejun Bai

{"title":"State-dependent neural signatures of autistic traits: evidence from fNIRS-based fractional amplitude of low-frequency fluctuation analysis during natural social interaction.","authors":"Shuyuan Feng, Yuqing Yuan, Mingliang Wang, Jianing Zhang, Lin Ding, Peng Zhang, Xuejun Bai","doi":"10.1097/WNR.0000000000002145","DOIUrl":"10.1097/WNR.0000000000002145","url":null,"abstract":"Autistic traits exist on a continuum within the general population, yet how these traits influence regional neural activity during real-world social interactions remains unclear. Using functional near-infrared spectroscopy (fNIRS), we investigated how autistic traits relate to the fractional amplitude of low-frequency fluctuations (fALFF) during both resting-state and real-time conversations in 62 high autistic trait and 58 low autistic trait neurotypical adults. While resting-state differences were minimal, significant group differences emerged during conversation. Specifically, individuals with high autistic traits showed lower ΔfALFF in the right superior temporal gyrus, with the largest differences observed during emotionally positive topics. Interestingly, although fALFF strongly correlated with functional connectivity across both states, only ΔfALFF demonstrated sensitivity to autistic traits. These findings reveal state-dependent neural differences linked to autistic traits, emphasizing the importance of studying brain activity during naturalistic social interactions. Our results provide new insights into how autistic traits modulate neural processing during dynamic social contexts and suggest fALFF change as a sensitive marker for studying social processing differences.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"267-271"},"PeriodicalIF":1.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458787","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}

引用次数: 0

Lipid droplets deposition in perihematoma tissue is associated with neurological dysfunction after intracerebral hemorrhage. 脑出血后血肿周围组织脂滴沉积与神经功能障碍有关。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-19 Epub Date: 2025-02-26 DOI: 10.1097/WNR.0000000000002136

Zhangze Wu, Quan Zhao, Ziqi Hu, Dongsheng Jiao

{"title":"Lipid droplets deposition in perihematoma tissue is associated with neurological dysfunction after intracerebral hemorrhage.","authors":"Zhangze Wu, Quan Zhao, Ziqi Hu, Dongsheng Jiao","doi":"10.1097/WNR.0000000000002136","DOIUrl":"10.1097/WNR.0000000000002136","url":null,"abstract":"Secondary brain injury following intracerebral hemorrhage (ICH) significantly reduces patients' quality of life due to impaired neurological function. Lipid droplets are implicated in secondary brain injury in various central nervous system diseases. Thus, the role and mechanisms of lipid droplets in secondary brain injury post-ICH require further investigation. We analyzed the changes of genes related to lipid metabolism in brain tissue of ICH mice. Lipid droplets around the hematoma were detected by BODIPY staining. Mice received intraperitoneal injections of Triacsin C (10 mg/kg, once daily) after ICH. Subsequently, neuronal damage was evaluated using TUNEL and Nissl staining, and ethological tests assessed sensorimotor function. After ICH, notable changes occurred in lipid metabolism pathways and genes (Plin2, Ucp2, Apoe), and a large number of lipid droplets accumulated around the hematoma. Triacsin C significantly reduced lipid droplets deposition, decreased neuronal damage, and improved sensory and motor functions. Peripheral administration to prevent lipid droplets formation can greatly reduce nerve damage and enhance nerve function. Our findings indicate that targeting lipid droplets could be a promising treatment for ICH.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"239-246"},"PeriodicalIF":1.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458784","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}

引用次数: 0

Gamma-aminobutyric acid and glutamate/glutamine associations with tinnitus and hearing loss. γ -氨基丁酸和谷氨酸/谷氨酰胺与耳鸣和听力损失的关系。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-05 Epub Date: 2025-02-12 DOI: 10.1097/WNR.0000000000002137

Rafay Ali Khan, Zepeng Wang, Ruiyang Zhao, Gibbeum Kim, Fan Lam, Fatima Tazeena Husain

{"title":"Gamma-aminobutyric acid and glutamate/glutamine associations with tinnitus and hearing loss.","authors":"Rafay Ali Khan, Zepeng Wang, Ruiyang Zhao, Gibbeum Kim, Fan Lam, Fatima Tazeena Husain","doi":"10.1097/WNR.0000000000002137","DOIUrl":"10.1097/WNR.0000000000002137","url":null,"abstract":"The present study aimed to evaluate the association between concentrations of the metabolites gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx), which have predominantly inhibitory and excitatory effects on neural function, respectively, in adults with tinnitus and hearing loss, those with only hearing loss, and controls with neither condition. Metabolite concentrations in all three participant groups were assessed via magnetic resonance spectroscopic imaging in auditory and fronto-parietal regions. The concentration of a third metabolite, creatine (Cre) was also acquired. Ratios of GABA/Cre, Glx/Cre, and Glx/GABA were compared across six manually delineated regions of interest (ROIs). Neither GABA/Cre nor Glx/Cre showed significant group differences in any of the six ROIs. For the Glx/GABA ratio, group-level differences were seen only in the right auditory cortex, where the control group had a significantly larger ratio than the group with tinnitus and hearing loss. While results largely did not replicate previous human work in this area, we cannot exclude the possibility of a neurochemical mechanism underlying any causal relationship between hearing loss and tinnitus, particularly given the finding of altered balance in excitatory/inhibitory metabolites in the right auditory cortex. In the context of previous work, the right auditory cortex is highlighted as a particular region of interest for further investigation. Methodological differences in human studies and inconsistent findings in animal studies have thus far impeded the field's ability to gain direct insight into the relationship between tinnitus and hearing loss, and so we make some suggestions to help design future studies.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"196-201"},"PeriodicalIF":1.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458781","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}

引用次数: 0

Electroacupuncture preconditioning alleviates cortical neuronal injury in cerebral ischemia-reperfusion by rebalancing HES1 and NF-κB expression. 电针预处理通过重新平衡HES1和NF-κB的表达，减轻脑缺血再灌注时皮层神经元的损伤。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-05 Epub Date: 2025-02-12 DOI: 10.1097/WNR.0000000000002142

Yegui Zhang, Jisheng Wang, Shi Huang, Min Liu, Yingdi Zhao, Zhiliang Xu, Xiuling Zhu

{"title":"Electroacupuncture preconditioning alleviates cortical neuronal injury in cerebral ischemia-reperfusion by rebalancing HES1 and NF-κB expression.","authors":"Yegui Zhang, Jisheng Wang, Shi Huang, Min Liu, Yingdi Zhao, Zhiliang Xu, Xiuling Zhu","doi":"10.1097/WNR.0000000000002142","DOIUrl":"10.1097/WNR.0000000000002142","url":null,"abstract":"The roles of Hairy Enhancer of Split 1 (HES1) and nuclear factor kappa B (NF-κB) in neuronal injury following cerebral ischemia have been well established. However, the relationship between electroacupuncture preconditioning-induced neuroprotection and these signaling pathways remains unclear. This study aimed to investigate the effects of electroacupuncture pretreatment on the expression of HES1 and NF-κB in the cortex of rats subjected to cerebral ischemia/reperfusion and to explore the underlying mechanisms. A total of 36 male Sprague-Dawley rats were randomized into three groups: sham, model, and electroacupuncture pretreatment ( n = 12 per group). Cerebral ischemia/reperfusion was induced using the middle cerebral artery occlusion (MCAO) method. Rats in the electroacupuncture group received daily electroacupuncture stimulation at 'Baihui' and 'Dazhui' acupoints 1 week prior to MCAO. Neurological function scores, 2,3,5-triphenyltetrazolium chloride staining for cerebral infarction, Nissl staining for neuronal cell survival, and immunohistochemical detection of HES1 and NF-κB expression in the cerebral cortex were assessed. Compared to the sham group, the model group exhibited significant neurological deficits, extensive cerebral infarction, decreased neuronal survival, and increased expression of HES1 and NF-κB ( P < 0.01). In contrast, electroacupuncture pretreatment significantly improved neurological function scores ( P < 0.01), reduced cerebral infarction ( P < 0.01), increased neuronal survival ( P < 0.05), and decreased the expression of HES1 and NF-κB ( P < 0.01). These findings suggest that electroacupuncture preconditioning may mitigate brain injury in cerebral ischemia/reperfusion rats by downregulating the expression of HES1 and NF-κB, thereby reducing inflammatory damage and enhancing cerebral ischemia tolerance.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"230-237"},"PeriodicalIF":1.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458778","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}

引用次数: 0

Enhanced cerebellar climbing fiber-Purkinje cell synaptic transmission via corticotropin-releasing factor receptor 2 during the chronic phase of spinal cord injury mice. 脊髓损伤小鼠慢性期通过促肾上腺皮质激素释放因子受体2增强小脑攀爬纤维-浦肯野细胞突触传递。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-05 Epub Date: 2025-02-12 DOI: 10.1097/WNR.0000000000002141

Wen-Cai Weng, Ying-Han Xu, De-Lai Qiu, Chun-Ping Chu

{"title":"Enhanced cerebellar climbing fiber-Purkinje cell synaptic transmission via corticotropin-releasing factor receptor 2 during the chronic phase of spinal cord injury mice.","authors":"Wen-Cai Weng, Ying-Han Xu, De-Lai Qiu, Chun-Ping Chu","doi":"10.1097/WNR.0000000000002141","DOIUrl":"10.1097/WNR.0000000000002141","url":null,"abstract":"Spinal cord injury (SCI) causes interruption of external information input from the spinal cord to the cerebellum. We here investigated the effect of SCI on mouse cerebellar climbing fiber-Purkinje cell (CF-PC) synaptic transmission. The SCI was caused at T10 using 6-week-old ICR mice. Mice recovered 4 weeks after surgery, the spontaneous complex spike (CS) activity of PC was recorded using cell-attached recording and whole-cell recording method in urethane-anesthetized mice cerebellar Crus II. The CF-PC excitatory postsynaptic currents (EPSCs) were evoked by paired electrical stimulation of CF in cerebellar slices to evaluate the changes of CF-PC synaptic transmission and paired-pulse ratio (PPR). The results showed that the number of spikelets, duration of spontaneous CS, and pause of simple spike firing were significantly increased in SCI than that in sham group. Application of a nonselective corticotropin-releasing factor receptor (CRF-R) antagonist significantly decreased spontaneous CS activity in SCI group but not in sham group. The enhanced CS activity in SCI mice was significantly decreased by a selective CRF-R2 antagonist but not a specific CRF-R1 antagonist. The amplitude of CF-PC EPSC1 was large accompanied by a lower PPR in SCI group than that in sham group. Blockade of CRF-R2 antagonist significantly decreased the amplitude of EPSC1 and increased PPR in SCI group. SCI induces enhancement of the spontaneous CS activity and CF-PC synaptic transmission via CRF-R2 in mouse cerebellar cortex, which suggests that remodeling of CF-PC synaptic transmission occurred in cerebellar cortex after SCI.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"223-229"},"PeriodicalIF":1.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458780","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}

引用次数: 0

CB1 receptor coupling to extracellular regulated kinase via multiple Gαi/o isoforms. CB1受体通过多种Gαi/o亚型偶联到细胞外调节激酶。

IF 1.6 4区医学

Neuroreport Pub Date : 2025-03-05 Epub Date: 2025-02-12 DOI: 10.1097/WNR.0000000000002138

Boyd R Rorabaugh, Daniel J Morgan

{"title":"CB1 receptor coupling to extracellular regulated kinase via multiple Gαi/o isoforms.","authors":"Boyd R Rorabaugh, Daniel J Morgan","doi":"10.1097/WNR.0000000000002138","DOIUrl":"10.1097/WNR.0000000000002138","url":null,"abstract":"Cannabinoid type 1 receptors (CB 1 Rs) play important roles in regulating neurotransmitter release, synaptic plasticity, cell differentiation, and survival. CB 1 R is coupled via pertussis toxin (PTX)-sensitive Gαi/o proteins to the activation of extracellular regulated kinase (ERK) signaling. However, there are multiple Gαi/o isoforms, and it is unknown which of these isoforms is responsible for CB 1 R-induced phosphorylation of ERK. The purpose of this study was to determine which Gαi/o isoform(s) couple CB 1 R to ERK phosphorylation. HEK293 cells stably expressing the mouse CB 1 R (CB 1 R-HEK cells) were transfected with either pcDNA3.1 or pcDNA3.1 encoding PTX-insensitive mutants of Gαo, Gαi1, Gαi2, or Gαi3. PTX was used to inactivate endogenous Gαi/o isoforms before cells were treated with vehicle, delta-9-tetrahydrocannabinol (∆ 9 -THC), or CP55940 and ERK phosphorylation was measured by western blotting. CP55940 induced robust phosphorylation of ERK in cells transfected with vector alone. This effect was completely abolished by PTX treatment. CP55940-induced ERK phosphorylation was rescued by expression of PTX-insensitive forms of Gαo, Gαi1, Gαi2, or Gαi3, indicating that the CB1 receptor can couple to ERK phosphorylation through each of these Gαi/o isoforms. Consistent with its actions as a partial agonist, ∆ 9 -THC induced nominal (two to four-fold) increases in ERK phosphorylation that did not reach statistical significance except in cells transfected with PTX-insensitive Gαi3. These data demonstrate that CB 1 R can couple to ERK phosphorylation through Gαo, Gαi1, Gαi2, or Gαi3 when stimulated with CP55940 (full agonist). However, ∆ 9 -THC (partial agonist)-induced ERK activation might require high levels of Gαi3 expression.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"191-195"},"PeriodicalIF":1.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0