Neuroscience Letters最新文献_第6页

Short-term immobilization impairs pointing direction programming and early motor control processes 短期固定化损害指向编程和早期运动控制过程。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-11 DOI: 10.1016/j.neulet.2025.138446

C.R. Scotto, F.R. Danion, Y. Blandin, L. Toussaint

Short-term limb immobilization is a valuable method for studying the contribution of proprioception since it temporarily reduces sensory and motor inputs. While several studies have shown that immobilization impairs cognitive and sensorimotor processes, none have yet demonstrated how it could specifically impact the programming of movement direction. Here, participants (N = 32) made uncorrected pointing movements toward five visual targets located in different directions − but requiring constant amplitude − without benefiting from any visual feedback on the hand. Pointing was performed on two consecutive days by Control and Immobilized participants, the latter of whom had worn a splint on the right arm during this 24 h period. Results showed that immobilization increased the duration of movement planning (i.e., longer reaction time) necessary to specify hand-path direction. A greater counterclockwise directional bias was observed at peak acceleration in the Immobilized group and persisted until the uncorrected movement offset. These results suggest that immobilization impacts direction programming as well as early motor control processes. We argue that proprioception deprivation impairs the perception of limb position, leading to both slower and less accurate motor command selection. Overall, we interpret that the lack of proprioceptive feedback and efference copies may influence the accuracy of movement planning after 24 h of immobilization, possibly reflecting changes in processes related to internal model mechanisms.

短期肢体固定是研究本体感觉贡献的一种有价值的方法，因为它暂时减少了感觉和运动输入。虽然有几项研究表明，不动会损害认知和感觉运动过程，但还没有研究表明它是如何具体影响运动方向的编程的。在这里，参与者（N = 32）对位于不同方向的五个视觉目标进行了未经纠正的指向运动-但需要恒定的振幅-没有从任何手部视觉反馈中受益。连续两天由对照组和固定组的参与者进行指指，后者在这24小时内在右臂上佩戴夹板。结果表明，固定化增加了指定手路方向所需的运动规划时间（即更长的反应时间）。在固定组中，在峰值加速度时观察到更大的逆时针方向偏差，并持续到未纠正的运动偏移。这些结果表明，固定化影响方向规划和早期运动控制过程。我们认为，本体感觉剥夺损害了肢体位置的感知，导致运动指令选择更慢和更不准确。总的来说，我们认为缺乏本体感觉反馈和影响拷贝可能会影响24 h固定后运动规划的准确性，这可能反映了与内部模型机制相关的过程的变化。

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引用次数: 0

Expression of serotonin transporter (SERT) and receptors 5-HTR1A and 5-HTR2A in an animal model of hypothermia 低温动物模型中血清素转运体（SERT）和受体5-HTR1A和5-HTR2A的表达

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-11 DOI: 10.1016/j.neulet.2025.138448

Andrei Negoiţă , Bogdan Amuzescu , Dan Florin Mihăilescu , Daniel Dumitru Banciu , Adela Banciu

The role of anterior hypothalamus and preoptic area in thermoregulation has been studied since the late 19^th century (Charles Richet 1884, Aronsohn&Sachs 1885), and thermosensitive neurons have been recorded in these areas. Numerous animal studies with injection of serotonergic agonists or antagonists proved activation of thermoregulatory responses, and complex serotonergic circuits with origin in dorsal raphe nucleus (DRN) and projection in hypothalamus and preoptic area (POA), nucleus accumbens (Acc), and central amygdala were identified. We assessed the expression of serotonin transporter SERT, 5-HT1A and 5-HT2A receptors at mRNA and protein level in several brain regions: brainstem raphe, hypothalamus, Acc and POA, amygdala, piriform cortex (Pir) in adult male CD1 mice kept 4 h/day at 4 °C or normal temperature (control) for 1–2 months. For qRT-PCR total RNA was extracted from fresh samples with a GenElute™ kit (Sigma), followed by RT and qPCR with hydrolysis probes (Applied Biosystems). For immunofluorescence 200 µm slices were cut from fixed brains and stained with primary antibodies ASR-021, ASR-033, AMT-004 (Alomone Labs) and secondary antibody N2404-Ab635P-L (NanoTag), co-stained with phalloidin-AlexaFluor488 and DAPI. We obtained statistically significant (two-tailed t test) increases in mRNA expression in hypothermia vs. control for SERT and 5-HT2A in the brainstem raphe and hypothalamus. Fluorescence intensities (averaged over small relevant regions and normalized to DAPI fluorescence) were higher in hypothermia for the two receptors in DRN and Acc, and similar to control levels in Pir and amygdala, proving activation of central serotonergic thermoregulatory circuits.

下丘脑前部和视前区在体温调节中的作用早在19世纪末就已被研究（Charles Richet 1884, Aronsohn&Sachs 1885），并在这些区域发现了热敏神经元。注射5 -羟色胺能激动剂或拮抗剂的大量动物研究证实了热调节反应的激活，并确定了复杂的5 -羟色胺能回路，该回路起源于中叶背核（DRN），投射于下丘脑和视前区（POA）、伏隔核（Acc）和中央杏仁核。我们在4 °C或正常温度（对照）下保持4 h/d，持续1-2 个月的成年雄性CD1小鼠中，评估了5-羟色胺转运体SERT、5-HT1A和5-HT2A受体在脑干中叶、下丘脑、Acc和POA、杏仁核、梨状皮质（Pir）等几个脑区mRNA和蛋白水平的表达。对于qRT-PCR，使用GenElute™试剂盒（Sigma）从新鲜样品中提取总RNA，然后使用水解探针（Applied Biosystems）进行RT和qPCR。免疫荧光切片取自固定脑，取200 µm切片，用一抗ASR-021、ASR-033、AMT-004 （Alomone Labs）和二抗N2404-Ab635P-L （NanoTag）染色，用phalloidin-AlexaFluor488和DAPI共染色。我们获得了具有统计学意义（双尾t检验）的结果，与对照组相比，低温下脑干中缝和下丘脑中SERT和5-HT2A的mRNA表达增加。在低温下，DRN和Acc中的两种受体的荧光强度（在小相关区域平均并归一化为DAPI荧光）更高，并且与Pir和杏仁核中的对照水平相似，证明了中枢血清素能热调节回路的激活。

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引用次数: 0

Immunohistochemically-detected differential localization of CXCL14 in mouse cerebellum suggesting the presence of neuronal and glial forms of CXCL14 免疫组织化学检测小鼠小脑中CXCL14的差异定位提示CXCL14存在神经元和胶质形式。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-07 DOI: 10.1016/j.neulet.2025.138442

Hirohumi Suzuki , Toshiharu Yamamoto , Aya Hasegawa , Toru Tamaki , Jun-ya Komagata , Takayoshi Yamaga , Tetsu Akasaka , Ryu-ichiro Hata

In this study we compared staining profiles in mouse cerebellum, using two anti-CXCL14 antibodies, which we designated α and β. The α anti-CXCL14 antibody labeled Purkinje neurons; this was confirmed by double-immunofluorescence staining with calbindin D-28k, a marker for Purkinje neurons. The β anti-CXCL14 antibody marked Bergmann glia; this was confirmed by combinational staining with glial fibrillary acidic protein, a marker for Bergmann glia. Both staining profiles were abolished by preabsorption of each antibody with recombinant human CXCL14. Western blot analyses using these two antibodies indicated that they both recognized recombinant human and mouse CXCL14s, which migrated at approximately a 12 kDa position. Furthermore, the α anti-CXCL14 antibody labeled major bands at approximately 15 kDa and 21 kDa, and a minor band at approximately 19 kDa from a Triton-X fraction of mouse cerebellum. However, there were no immunostaining bands from a Tris-HCl fraction. In contrast, the β anti-CXCL14 antibody labeled a band of approximately 18 kDa from a Tris-HCl fraction of cerebellum, but no immunoreactive bands were detected from a Triton-X fraction. These results suggest that mouse cerebellum has at least two forms of CXCL14; presumably a neuronal form and a glial form.

在这项研究中，我们比较了小鼠小脑的染色谱，使用两种抗cxcl14抗体，我们命名为α和β。α抗cxcl14抗体标记浦肯野神经元；这是用calbindin D-28 k（浦肯野神经元的标记物）双免疫荧光染色证实的。β抗cxcl14抗体标记伯格曼胶质细胞；胶质原纤维酸性蛋白（Bergmann胶质的标记物）联合染色证实了这一点。通过重组人CXCL14预吸收每个抗体来消除两种染色谱。使用这两种抗体进行Western blot分析表明，它们都能识别重组的人和小鼠CXCL14s，其迁移位置约为12 kDa。此外，α抗cxcl14抗体标记了小鼠小脑Triton-X部分约15 kDa和21 kDa的主要条带，以及约19 kDa的次要条带。然而，Tris-HCl部分没有免疫染色带。相比之下，β抗cxcl14抗体标记了来自小脑Tris-HCl片段的约18 kDa的条带，但未检测到来自Triton-X片段的免疫反应条带。这些结果表明，小鼠小脑至少有两种形式的CXCL14；大概是神经元形式和胶质形式。

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引用次数: 0

Sensory afferents in the mammary papilla are eliminated during the lactation 乳突中的感觉传入在哺乳期被消除。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-04 DOI: 10.1016/j.neulet.2025.138441

Kei Nakayama , Kotoko Suzuki , Yukiko Marunaka , Mari Kondo , Yuji Yokouchi , Naoki Takeda , Kenichi Yamamura , Hiroshi Hasegawa

Importance of breastfeeding is well recognized, since it supports the survival of mammalian infants. The mammary papilla, a specialized skin region for breastfeeding, acts as a vital interface between mother and infant: perceiving the suckling to trigger the milk ejection reflex in mother and transporting milk from mother to infants. Despite its crucial roles in breastfeeding, the histological and cellular changes in the mammary papilla during lactation remain poorly understood. In this study, we focused on the sensory afferent projection mediating somatosensory perception. Our observation revealed that the mammary papilla is innervated by non-peptidergic C-fibers, which engage in the mechanical nociception. Moreover, we found that these sensory afferents are eliminated in the mammary papilla of lactating females. These results propose the lactation-associated elimination of sensory afferents in the mammary papilla as a novel mechanism adaptive for the breastfeeding.

母乳喂养的重要性是公认的，因为它支持哺乳动物婴儿的生存。乳突是母乳喂养的一个特殊皮肤区域，它是母亲和婴儿之间的重要接口：感知哺乳，触发母亲的乳汁反射，并将乳汁从母亲输送给婴儿。尽管它在母乳喂养中起着至关重要的作用，但哺乳期间乳腺乳头的组织学和细胞变化仍然知之甚少。在本研究中，我们重点研究了感觉传入投射介导的体感觉知觉。我们的观察表明，乳腺乳头受非肽能性c -纤维支配，参与机械性伤害感觉。此外，我们发现这些感觉传入在哺乳期雌性的乳腺乳头中被消除。这些结果表明，哺乳相关的乳腺乳头感觉传入的消除是一种适应母乳喂养的新机制。

引用次数: 0

Involvement of CXCR2 in chronic postsurgical pain occurrence through ERK/p38 activation CXCR2通过ERK/p38激活参与慢性术后疼痛的发生。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-03 DOI: 10.1016/j.neulet.2025.138440

TianYu Ge , Xi Chen , Chang Liu , SaiSai Huang

Chronic postsurgical pain (CPSP) is a global concern associated with significant health and economic issues for patients. We investigated the effects of C-X-C motif chemokine receptor 2 (CXCR2) related signal transduction mechanisms on CPSP in a rat skin muscle incision and retraction (SMIR) model. Following model establishment, glial cells in the spinal dorsal horn were activated, and the expression of inflammatory factors (tumor necrosis factor (TNF)-α and interleukin (IL)-1β increased. The SMIR group demonstrated elevated expression of CXCR2, phosphorylated ERK (p-ERK), and phosphorylated p38 (p-p38) in the spinal dorsal horn. After intrathecal injection of the CXCR2 antagonist SB225002, the rats’ pain threshold increased, accompanied by reduced expression of inflammatory factors and reversal of glial cell activation. Additionally, primary microglial cells induced by lipopolysaccharide were used as an in vitro model. Transfection with si-CXCR2 led to decreased expression of p-ERK and p-p38 in microglial cells, along with lower TNF-α and IL-1β levels in the cell supernatant. These results indicate that CXCR2 activates spinal glial cells via the ERK/p38 pathway, promoting neuroinflammation, and CPSP, whereas CXCR2 inhibition counteracts these effects and alleviates CPSP.

慢性术后疼痛（CPSP）是一个全球性的问题，与患者的重大健康和经济问题有关。我们研究了C-X-C基序趋化因子受体2 （CXCR2）相关信号转导机制对大鼠皮肤肌肉切开和收缩（SMIR）模型CPSP的影响。模型建立后，脊髓背角神经胶质细胞被激活，炎症因子(肿瘤坏死因子（TNF)-α和白细胞介素(IL)-1β）表达升高。SMIR组显示脊髓背角中CXCR2、磷酸化ERK （p-ERK）和磷酸化p38 （p-p38）的表达升高。鞘内注射CXCR2拮抗剂SB225002后，大鼠疼痛阈值升高，炎症因子表达降低，胶质细胞活化逆转。此外，还采用脂多糖诱导的原代小胶质细胞作为体外模型。转染si-CXCR2可降低小胶质细胞中p-ERK和p-p38的表达，同时降低细胞上清中TNF-α和IL-1β的水平。这些结果表明，CXCR2通过ERK/p38通路激活脊髓胶质细胞，促进神经炎症和CPSP，而CXCR2抑制抵消这些作用并减轻CPSP。

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引用次数: 0

Laughing your… brain off. New insights on the adaptive meaning of humour 社论：笑掉你的脑袋。幽默的适应性意义的新见解。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-01 DOI: 10.1016/j.neulet.2025.138411

Maria Elide Vanutelli , Mirella Manfredi

引用次数: 0

Stress-type specific changes of VIP signaling in limbic regions of the rat brain 应激型大鼠脑边缘区VIP信号的特异性变化。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-31 DOI: 10.1016/j.neulet.2025.138430

Federico Ferro , Veronica Fontebasso , Magali Basille-Dugay , David Vaudry , Karl Ebner

Vasoactive intestinal peptide (VIP) is a highly abundant neuropeptide in the central nervous system, implicated in the regulation of numerous behavioral and physiological functions, including the central stress response. Notably, VIP and its cognate receptors, VPAC1 and VPAC2, are widely expressed in brain areas implicated in stress and anxiety regulation such as the amygdala. However, the exact role of VIP in stress function is not fully understood. The present study therefore examined how acute or chronic stress affect VIP and VPAC receptor gene expression in specific limbic brain regions of Sprague-Dawley rats using quantitative real-time PCR. Acute stress via forced swim exposure significantly increased VIP expression in the central amygdala (CeA) by 200 %, and in the medial amygdala (MeA) by 350 %. It also elevated VPAC1 receptor expression in the hypothalamic paraventricular nucleus (PVN), basolateral amygdala (BLA), and CeA, and VPAC2 receptor expression in the bed nucleus of the stria terminalis (BNST) and BLA. Chronic unpredictable stress induced both overlapping and distinct patterns, including upregulation of the VPAC1 receptor expression in the PVN by 120 % and the VPAC2 receptor in the CeA by 280 %, accompanied by slight downregulation of VIP in the CeA. These findings highlight a stress-duration-dependent and region-specific regulation of the VIP/VPAC receptor system and its potential role in modulating stress-related neural circuits.

血管活性肠肽（Vasoactive intestinal peptide， VIP）是一种在中枢神经系统中含量丰富的神经肽，参与调节多种行为和生理功能，包括中枢应激反应。值得注意的是，VIP及其同源受体VPAC1和VPAC2在涉及压力和焦虑调节的大脑区域（如杏仁核）广泛表达。然而，VIP在应激功能中的确切作用尚不完全清楚。因此，本研究利用实时荧光定量PCR检测了急性或慢性应激对Sprague-Dawley大鼠特定边缘脑区VIP和VPAC受体基因表达的影响。通过强迫游泳暴露引起的急性应激显著增加中央杏仁核（CeA）中VIP的表达200 %，内侧杏仁核（MeA）中VIP的表达350 %。上调下丘脑室旁核（PVN）、基底外侧杏仁核（BLA）和CeA中VPAC1受体的表达，上调终纹床核（BNST）和BLA中VPAC2受体的表达。慢性不可预测的应激诱导了重叠和不同的模式，包括PVN中VPAC1受体表达上调120 %，CeA中VPAC2受体表达上调280 %，并伴有CeA中VIP的轻微下调。这些发现强调了应激持续时间依赖性和区域特异性的VIP/VPAC受体系统的调节及其在调节应激相关神经回路中的潜在作用。

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引用次数: 0

Neuro-protection of swertisin against impairment induced by Aβ25-35 by acting on COX-2 to up-regulate 2-AG and suppressing neuroinflammation 獐牙菜素通过作用于COX-2上调2-AG和抑制神经炎症对Aβ25-35损伤的神经保护作用

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-28 DOI: 10.1016/j.neulet.2025.138429

Jiang Wu , Lijin Zhou , Chao Lang

Ziziphi Spinosae Semen (Suan Zao Ren) is a traditional Chinese medicine with the functions of nourishing the heart and liver, calming the mind, and stopping sweating. Swertisin, one of the main active ingredients in Ziziphi Spinosae Semen, has a wide range of pharmacological effects such as anti-inflammation, anti-oxidation, and enhancement of learning and memory. Based on the Aβ cascade and the neuroinflammatory theory, combined with the anti-inflammatory neuroprotective effect of endocannabinoid 2-AG, this work integrated modern biochemical technology methods such as liquid chromatography-mass spectrometry, Western blot, and electrophysiological technique to explore the neuroprotective effects and potential mechanism of swertisin on the Alzheimer’s disease (AD) model induced by Aβ_25-35. The results showed that swertisin relieved impairment of learning and memory caused by Aβ_25-35 on hippocampus slice by decreasing COX-2 expression and inhibiting COX-2 activity to up-regulate the endogenous 2-AG, and suppressing neuroinflammation and neuronal apoptosis via CB1R-dependent NF-κB pathway. It was further discovered that swertisin protected the primary hippocampal neurons, reduced over-expression of COX-2, and relieved the neuroinflammatory against Aβ_25-35 through the CB1R-dependent NF-κB signaling pathway. Finally, it was confirmed that swertisin alleviated BV-2 cell apoptosis induced by Aβ_25-35. These results help us understand the mechanism of swertisin against AD and promote the development of related drugs and healthy products.

酸枣仁（酸枣仁）是一种传统的中药，具有滋补心肝、安神、止汗的作用。獐牙菜素是酸枣中的主要活性成分之一，具有抗炎、抗氧化、增强学习记忆等广泛的药理作用。本研究基于Aβ级联反应和神经炎症理论，结合内源性大麻素2-AG的抗炎神经保护作用，结合液相色谱-质谱、Western blot、电生理技术等现代生化技术手段，探讨獐角菜素对Aβ25-35诱导的阿尔茨海默病（AD）模型的神经保护作用及其潜在机制。结果表明，獐尾鱼素可通过降低COX-2表达和抑制COX-2活性上调内源性2-AG，通过cb1r依赖的NF-κB通路抑制神经炎症和神经元凋亡，缓解a - β25-35在海马片上引起的学习记忆障碍。进一步发现獐牙菜素通过cb1r依赖的NF-κB信号通路，保护海马原代神经元，降低COX-2的过表达，减轻a - β25-35的神经炎症。最后证实獐牙菜素可减轻a - β25-35诱导的BV-2细胞凋亡。这些结果有助于我们了解獐牙菜素抗AD的作用机制，促进相关药物和保健品的开发。

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引用次数: 0

Acute exposure to vaporized cannabidiol remodels coding and noncoding transcriptomes in the mouse striatum 急性暴露于汽化大麻二酚重塑编码和非编码转录组在小鼠纹状体。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-26 DOI: 10.1016/j.neulet.2025.138428

Mi Ran Choi , Chaeeun Park , Jihun Kim , Jeong-Hyeon Heo , Seok Hwan Chang , Han-Na Kim , Yeung Bae Jin , Sang-Rae Lee

Cannabidiol (CBD) is increasingly consumed via vaping, but its acute molecular impact on the striatum, a critical hub for motor control and reward processing that is highly sensitive to cannabinoid modulation, remains poorly understood. This study investigated differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the striatum after acute exposure to vaporized CBD. Male ICR mice (n = 5 per group) were exposed to vaporized CBD oil (50 mg) and striatal tissues were collected 24 h later. Differentially expressed mRNAs and lncRNAs were identified using total RNA sequencing and mRNA–lncRNA co-expression networks were constructed. Selected transcripts were validated using qRT-PCR and discriminative capacity was assessed by ROC analysis. CBD exposure altered the expression of 931 mRNAs and 229 lncRNAs. GO and KEGG analyses revealed bidirectional regulation of pathways involved in neural development and synaptic transmission, including both up- and downregulated genes in categories such as glutamatergic synapse. Ion transport genes (Trpm2, Tmem63a, Tmem175, Glrb) were robustly upregulated, while genes involved in excitatory synaptic structure (Dlgap2, Shisa9, Tac1) and dopaminergic-associated pathways (Drd3, Oxt) were downregulated. mRNA–lncRNA network analysis highlighted regulatory hubs including NONMMUT114016.1 and NONMMUT057055.2, and ROC analysis identified strong biomarker candidates such as Tmem175, Ptprd, NONMMUT042895.2, and NONMMUT151847.1. These findings indicate that acute CBD vaping induces widespread transcriptomic remodeling in the striatum, enhancing ion transport and inhibitory signaling while suppressing excitatory and dopaminergic pathways. This study provides the first comprehensive striatal transcriptome profiling of coding and noncoding RNAs in response to vaporized CBD.

大麻二酚（CBD）越来越多地通过电子烟消耗，但其对纹状体的急性分子影响仍然知之甚少，纹状体是运动控制和奖励处理的关键枢纽，对大麻素调节高度敏感。本研究研究了急性暴露于汽化CBD后纹状体中长链非编码rna （lncRNAs）和mrna的差异表达。雄性ICR小鼠（n = 每组5只）暴露于蒸发的CBD油（50 mg）， 24 h后收集纹状体组织。利用总RNA测序技术鉴定差异表达mrna和lncrna，构建mRNA-lncRNA共表达网络。选取的转录本采用qRT-PCR验证，并采用ROC分析评估其鉴别能力。CBD暴露改变了931个mrna和229个lncrna的表达。GO和KEGG分析揭示了参与神经发育和突触传递的双向调控通路，包括谷氨酸突触等类别的上调和下调基因。离子转运基因（Trpm2、Tmem63a、Tmem175、Glrb）显著上调，而参与兴奋性突触结构的基因（dgap2、Shisa9、Tac1）和多巴胺能相关通路（Drd3、Oxt）下调。mRNA-lncRNA网络分析突出了调控枢纽，包括NONMMUT114016.1和NONMMUT057055.2， ROC分析确定了强有力的生物标志物候选，如Tmem175、Ptprd、NONMMUT042895.2和NONMMUT151847.1。这些发现表明，急性CBD雾化诱导纹状体广泛的转录组重塑，增强离子运输和抑制信号传导，同时抑制兴奋和多巴胺能通路。这项研究提供了第一个全面的纹状体转录组分析编码和非编码rna对汽化CBD的反应。

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引用次数: 0

Site-Specific Regulation of Tau phosphorylation by MAPK pathways during HFS-Induced synaptic plasticity in the Rat hippocampus hfs诱导大鼠海马突触可塑性过程中MAPK通路对Tau磷酸化的位点特异性调控。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-21 DOI: 10.1016/j.neulet.2025.138426

Cem Süer, Burak Tan, Nurcan Dursun, Bilal Koşar, Ercan Babur

This study examined the role of MAPKs in Tau phosphorylation and synaptic plasticity at perforant pathway–dentate gyrus (PP–DG) synapses following high-frequency stimulation (HFS). In vivo experiments were conducted on adult male Wistar rats under urethane anesthesia. Field potentials (fEPSP and PS) were recorded in the DG granule cell layer in response to PP stimulation. Western blotting assessed total and phosphorylated levels of Tau, ERK1/2, JNK, and P38 MAPK in HFS-induced hippocampus. MAPK inhibition disrupted early somatic potentiation when applied during induction, and JNK inhibition alone impaired late potentiation. Reduced somatic activity correlated with decreased MAPK phosphorylation and Tau phosphorylation at Ser422. Findings suggest that ERK1/2, JNK, and P38 are essential for Tau phosphorylation at Ser422 in HFS-induced hippocampal synapses.

本研究探讨了MAPKs在高频刺激（HFS）后穿孔通路-齿状回（PP-DG）突触Tau磷酸化和突触可塑性中的作用。以成年雄性Wistar大鼠为实验对象，在氨基甲酸乙酯麻醉下进行体内实验。在PP刺激下记录DG颗粒细胞层的场电位（fEPSP和PS）。Western blotting检测hfs诱导海马中Tau、ERK1/2、JNK和P38 MAPK的总水平和磷酸化水平。当在诱导过程中应用MAPK抑制时，会破坏早期体细胞增强，而JNK单独抑制会破坏晚期增强。体细胞活性降低与MAPK磷酸化和Tau蛋白Ser422磷酸化降低相关。研究结果表明，ERK1/2、JNK和P38对于hfs诱导的海马突触Ser422位点的Tau磷酸化至关重要。

引用次数: 0