Neuroscience Letters最新文献_第6页

Artemisinin attenuates quinolinic acid-induced neurotoxicity by suppressing neuroinflammatory and apoptotic gene expression in rats 青蒿素通过抑制大鼠神经炎症和凋亡基因表达来减轻喹啉酸诱导的神经毒性。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-13 DOI: 10.1016/j.neulet.2025.138449

Richmond Arthur , Uma Shanker , Manjinder Singh , Thakur Gurjeet Singh , Puneet Kumar

Neurotoxicity, characterised by the structural and functional disruption of the nervous system, remains a major contributor to the pathophysiology of neurodegenerative disorders. It is mostly caused by oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation, which results in gradual neuronal damage and death. Despite breakthroughs in understanding its underlying principles, effective therapeutic strategies to alleviate neurotoxic harm are still limited. Beyond its antimalarial action, artemisinin, a sesquiterpene lactone obtained from Artemisia annua, has recently attracted attention for its strong anti-inflammatory, antioxidant, and neuroprotective qualities. QA was bilaterally injected directly into the rat striatum to simulate neurotoxic conditions, followed by a 21-day artemisinin treatment. On days 0, 14, and 21, motor coordination was evaluated through behavioural assessments, including narrow beam walking, the open field test, and rotarod performance. Striatal homogenates were tested for oxidative stress parameters. qRT-PCR was used for molecular investigations. Hematoxylin and eosin staining was used to investigate histopathological changes in the striatum. Results indicated that artemisinin mitigated neurotoxicity in the experimental rats. It reduced oxidative stress and inflammatory and apoptotic markers in striatal homogenates. In conclusion, artemisinin efficiently reduced neurotoxic damage, indicating its promise as a potential neuroprotective alternative for neurodegenerative diseases.

神经毒性，以神经系统的结构和功能破坏为特征，仍然是神经退行性疾病病理生理学的主要贡献者。它主要由氧化应激、兴奋性毒性、线粒体功能障碍和神经炎症引起，导致逐渐的神经元损伤和死亡。尽管在理解其基本原理方面取得了突破，但有效的治疗策略仍然有限。青蒿素是一种从黄花蒿中提取的倍半萜内酯，除了具有抗疟疾作用外，最近还因其强大的抗炎、抗氧化和神经保护特性而引起了人们的注意。双侧直接将QA注射到大鼠纹状体中模拟神经毒性，随后给予21天的青蒿素治疗。在第0、14和21天，通过行为评估评估运动协调性，包括窄梁行走、开阔场地测试和旋转棒表现。检测纹状体匀浆的氧化应激参数。采用qRT-PCR进行分子分析。采用苏木精和伊红染色观察纹状体组织病理变化。结果表明，青蒿素可减轻实验大鼠的神经毒性。它可以降低纹状体匀浆中的氧化应激和炎症及凋亡标志物。总之，青蒿素有效地减少了神经毒性损伤，表明其有望成为神经退行性疾病的潜在神经保护替代品。

{"title":"Artemisinin attenuates quinolinic acid-induced neurotoxicity by suppressing neuroinflammatory and apoptotic gene expression in rats","authors":"Richmond Arthur , Uma Shanker , Manjinder Singh , Thakur Gurjeet Singh , Puneet Kumar","doi":"10.1016/j.neulet.2025.138449","DOIUrl":"10.1016/j.neulet.2025.138449","url":null,"abstract":"<div><div>Neurotoxicity, characterised by the structural and functional disruption of the nervous system, remains a major contributor to the pathophysiology of neurodegenerative disorders. It is mostly caused by oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation, which results in gradual neuronal damage and death. Despite breakthroughs in understanding its underlying principles, effective therapeutic strategies to alleviate neurotoxic harm are still limited. Beyond its antimalarial action, artemisinin, a sesquiterpene lactone obtained from <em>Artemisia annua</em>, has recently attracted attention for its strong anti-inflammatory, antioxidant, and neuroprotective qualities. QA was bilaterally injected directly into the rat striatum to simulate neurotoxic conditions, followed by a 21-day artemisinin treatment. On days 0, 14, and 21, motor coordination was evaluated through behavioural assessments, including narrow beam walking, the open field test, and rotarod performance. Striatal homogenates were tested for oxidative stress parameters. qRT-PCR was used for molecular investigations. Hematoxylin and eosin staining was used to investigate histopathological changes in the striatum. Results indicated that artemisinin mitigated neurotoxicity in the experimental rats. It reduced oxidative stress and inflammatory and apoptotic markers in striatal homogenates. In conclusion, artemisinin efficiently reduced neurotoxic damage, indicating its promise as a potential neuroprotective alternative for neurodegenerative diseases.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138449"},"PeriodicalIF":2.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530794","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

Reducing surgical complexity in SAH models: A modified approach for reliable early and long-term brain injury replication 降低SAH模型的手术复杂性：一种可靠的早期和长期脑损伤复制的改进方法。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-13 DOI: 10.1016/j.neulet.2025.138445

Xincan Zhao , Shuai Zhang , Shengming Jiang , Ziang Yan , Jianming Liao , Qi Tian , Chengli Liu , Wenrui Han , Guijun Wang , Lei Wang , Mingchang Li

Among subarachnoid hemorrhage (SAH) models, the endovascular perforation method is widely used but limited by complex procedures and low efficiency. In this study, we developed a modified SAH model in male C57BL/6 mice by permanently ligating the unilateral common carotid artery (CCA) while maintaining external carotid artery (ECA) patency. Using laser speckle imaging, neurological scoring, brain water content analysis, TUNEL-NeuN co-staining, and behavioral tests, we compared this modified model to the classical approach. The modified model replicated key early and long-term brain injury features—cerebral edema, neuronal apoptosis, hemodynamic changes and cognition impairment—while significantly reducing surgical time and mortality rate. Total cerebral perfusion 24 h post-SAH was higher, with no differences in edema, apoptosis, or neurological scores versus the classic ECA model. This modified SAH model offers a practical, efficient tool for translational SAH research without compromising pathophysiological accuracy.

在蛛网膜下腔出血（SAH）模型中，血管内穿孔法被广泛应用，但由于操作复杂和效率低而受到限制。在本研究中，我们通过永久结扎单侧颈总动脉（CCA），同时保持颈外动脉（ECA）通畅，建立了一种改良的雄性C57BL/6小鼠SAH模型。通过激光散斑成像、神经系统评分、脑含水量分析、TUNEL-NeuN共染色和行为测试，我们将这种改进的模型与经典方法进行了比较。改进后的模型复制了早期和长期脑损伤的关键特征——脑水肿、神经元凋亡、血流动力学改变和认知障碍，同时显著缩短了手术时间和死亡率。与经典ECA模型相比，sah后24 h的总脑灌注更高，水肿、细胞凋亡或神经学评分无差异。这种改进的SAH模型为翻译SAH研究提供了一种实用、有效的工具，而不影响病理生理学的准确性。

{"title":"Reducing surgical complexity in SAH models: A modified approach for reliable early and long-term brain injury replication","authors":"Xincan Zhao , Shuai Zhang , Shengming Jiang , Ziang Yan , Jianming Liao , Qi Tian , Chengli Liu , Wenrui Han , Guijun Wang , Lei Wang , Mingchang Li","doi":"10.1016/j.neulet.2025.138445","DOIUrl":"10.1016/j.neulet.2025.138445","url":null,"abstract":"<div><div>Among subarachnoid hemorrhage (SAH) models, the endovascular perforation method is widely used but limited by complex procedures and low efficiency. In this study, we developed a modified SAH model in male C57BL/6 mice by permanently ligating the unilateral common carotid artery (CCA) while maintaining external carotid artery (ECA) patency. Using laser speckle imaging, neurological scoring, brain water content analysis, TUNEL-NeuN co-staining, and behavioral tests, we compared this modified model to the classical approach. The modified model replicated key early and long-term brain injury features—cerebral edema, neuronal apoptosis, hemodynamic changes and cognition impairment—while significantly reducing surgical time and mortality rate. Total cerebral perfusion 24 h post-SAH was higher, with no differences in edema, apoptosis, or neurological scores versus the classic ECA model. This modified SAH model offers a practical, efficient tool for translational SAH research without compromising pathophysiological accuracy.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138445"},"PeriodicalIF":2.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530855","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

Intermittent mild skin cooling stimulation inhibits pineal melatonin secretion in urethane-anesthetized rats 间歇性轻度皮肤降温刺激抑制聚氨酯麻醉大鼠松果体褪黑素分泌。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-12 DOI: 10.1016/j.neulet.2025.138444

Nobuhiro Watanabe, Masamichi Moriya, Harumi Hotta

Skin thermal stimulation can induce reflexive autonomic nerve responses and thereby influence endocrine functions. Melatonin, secreted from the pineal gland primarily under sympathetic control, exerts various physiological functions including sleep–wake rhythm regulation. Although photostimulation is a well-known regulator of melatonin secretion, the effect of skin thermal stimulation remains unclear. In this study, we investigated whether intermittent mild cooling stimulation of the skin alters melatonin secretion from the pineal gland in urethane-anesthetized rats. Animals were artificially ventilated, and their rectal temperatures were maintained using a heating pad and a lamp. Using in vivo microdialysis, pineal perfusate was collected every 20 min for 100 min during the animal’s light phase and the melatonin concentrations were measured via ELISA. Intermittent cooling stimulation was applied to the skin of the trunk using a Peltier-based contact thermode by alternating the temperature between 30 °C and 15 °C (15 °C/s) for 20 min. Without cooling stimulation, the melatonin concentration in the pineal perfusate remained stable for 100 min. Cooling stimulation did not affect the melatonin concentration during application but reduced it for 40 min after the stimulation was discontinued. This suppression was abolished in rats with bilateral cervical sympathetic nerve transection. Our findings suggest that intermittent mild skin cooling stimulation reflexively suppresses pineal melatonin secretion through cervical sympathetic nerves.

皮肤热刺激可引起反射性自主神经反应，从而影响内分泌功能。褪黑素主要由松果体在交感神经控制下分泌，具有调节睡眠-觉醒节律等多种生理功能。虽然众所周知，光刺激是褪黑激素分泌的调节因子，但皮肤热刺激的作用尚不清楚。在这项研究中，我们研究了间歇性温和的皮肤冷却刺激是否会改变聚氨酯麻醉大鼠松果体的褪黑激素分泌。动物人工通风，用加热垫和灯保持直肠温度。采用体内微透析，在动物光照期每20 min收集100 min松果体灌注液，并通过ELISA测定褪黑激素浓度。使用基于peltier的接触式热模对躯干皮肤进行间歇性冷却刺激，温度在30 °C和15 °C（15 °C/s）之间交替20 分钟。在没有冷却刺激的情况下，松果体灌注液中的褪黑激素浓度在100 min内保持稳定。冷却刺激在应用过程中不影响褪黑激素浓度，但在刺激停止后40 分钟内降低褪黑激素浓度。这种抑制在双侧颈交感神经横断的大鼠中被消除。我们的研究结果表明，间歇性轻度皮肤冷却刺激反射性地抑制松果体褪黑素通过颈交感神经分泌。

{"title":"Intermittent mild skin cooling stimulation inhibits pineal melatonin secretion in urethane-anesthetized rats","authors":"Nobuhiro Watanabe, Masamichi Moriya, Harumi Hotta","doi":"10.1016/j.neulet.2025.138444","DOIUrl":"10.1016/j.neulet.2025.138444","url":null,"abstract":"<div><div>Skin thermal stimulation can induce reflexive autonomic nerve responses and thereby influence endocrine functions. Melatonin, secreted from the pineal gland primarily under sympathetic control, exerts various physiological functions including sleep–wake rhythm regulation. Although photostimulation is a well-known regulator of melatonin secretion, the effect of skin thermal stimulation remains unclear. In this study, we investigated whether intermittent mild cooling stimulation of the skin alters melatonin secretion from the pineal gland in urethane-anesthetized rats. Animals were artificially ventilated, and their rectal temperatures were maintained using a heating pad and a lamp. Using <em>in vivo</em> microdialysis, pineal perfusate was collected every 20 min for 100 min during the animal’s light phase and the melatonin concentrations were measured via ELISA. Intermittent cooling stimulation was applied to the skin of the trunk using a Peltier-based contact thermode by alternating the temperature between 30 °C and 15 °C (15 °C/s) for 20 min. Without cooling stimulation, the melatonin concentration in the pineal perfusate remained stable for 100 min. Cooling stimulation did not affect the melatonin concentration during application but reduced it for 40 min after the stimulation was discontinued. This suppression was abolished in rats with bilateral cervical sympathetic nerve transection. Our findings suggest that intermittent mild skin cooling stimulation reflexively suppresses pineal melatonin secretion through cervical sympathetic nerves.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138444"},"PeriodicalIF":2.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524064","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

Limited effects of the REV-ERB agonist SR9009 after mouse spinal cord contusion: Reduced acute pathology with unaffected functional recovery and chronic white matter loss REV-ERB激动剂SR9009在小鼠脊髓挫伤后的有限作用：减少急性病理，未受影响的功能恢复和慢性白质损失。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-12 DOI: 10.1016/j.neulet.2025.138443

Lukasz P. Slomnicki , Emily Hodges , Christine Armstrong , Johnny Morehouse , Darlene Burke , Sujata Saraswat Ohri , Thomas P. Burris , Michal Hetman

The ligand-regulated transcription factors REV-ERBα/NR1D1 and REV-ERBβ/NR1D2 are promising neuroprotective targets. Systemic administration of the REV-ERB agonist SR9009 has been shown to reduce neuroinflammation, limit tissue loss, and enhance functional recovery in several models of acute CNS injury. To evaluate its potential in spinal cord injury (SCI), a moderate contusion was induced at the T9 level in mice. SR9009 was administered intraperitoneally at 100 mg/kg per day (two 50 mg/kg doses at ZT1 and ZT12) for the first 7 days post-injury, when tissue damage is most pronounced in this model. At 3 days post-SCI, SR9009-treated mice exhibited reduced hematoma and decreased expression of transcripts associated with blood–spinal cord barrier disruption, inflammation, and cellular stress responses. However, hindlimb functional recovery remained unchanged throughout 6 weeks of follow-up, and no significant differences in white matter sparing were observed at study completion. These findings indicate that although SR9009 reduces acute activation of some secondary injury cascades, it does not promote long-term tissue preservation or functional recovery after contusive SCI in mice.

配体调控的转录因子rev - erba /NR1D1和rev - erbb β/NR1D2是有前景的神经保护靶点。在几种急性中枢神经系统损伤模型中，系统给药REV-ERB激动剂SR9009已被证明可以减少神经炎症，限制组织损失，并增强功能恢复。为了评估其在脊髓损伤（SCI）中的潜力，我们在T9水平诱导小鼠中度挫伤。SR9009以每天100 mg/kg的剂量（ZT1和ZT12两个50 mg/kg的剂量）在损伤后的前7 天腹腔注射，此时该模型中组织损伤最为明显。在脊髓损伤后3 天，sr9009治疗的小鼠表现出血肿减少，与血脊髓屏障破坏、炎症和细胞应激反应相关的转录物表达减少。然而，在6 周的随访中，后肢功能恢复保持不变，并且在研究结束时没有观察到白质保留的显著差异。这些发现表明，尽管SR9009降低了一些继发性损伤级联反应的急性激活，但它并不能促进小鼠挫伤性脊髓损伤后的长期组织保存或功能恢复。

{"title":"Limited effects of the REV-ERB agonist SR9009 after mouse spinal cord contusion: Reduced acute pathology with unaffected functional recovery and chronic white matter loss","authors":"Lukasz P. Slomnicki , Emily Hodges , Christine Armstrong , Johnny Morehouse , Darlene Burke , Sujata Saraswat Ohri , Thomas P. Burris , Michal Hetman","doi":"10.1016/j.neulet.2025.138443","DOIUrl":"10.1016/j.neulet.2025.138443","url":null,"abstract":"<div><div>The ligand-regulated transcription factors REV-ERBα/NR1D1 and REV-ERBβ/NR1D2 are promising neuroprotective targets. Systemic administration of the REV-ERB agonist SR9009 has been shown to reduce neuroinflammation, limit tissue loss, and enhance functional recovery in several models of acute CNS injury. To evaluate its potential in spinal cord injury (SCI), a moderate contusion was induced at the T9 level in mice. SR9009 was administered intraperitoneally at 100 mg/kg per day (two 50 mg/kg doses at ZT1 and ZT12) for the first 7 days post-injury, when tissue damage is most pronounced in this model. At 3 days post-SCI, SR9009-treated mice exhibited reduced hematoma and decreased expression of transcripts associated with blood–spinal cord barrier disruption, inflammation, and cellular stress responses. However, hindlimb functional recovery remained unchanged throughout 6 weeks of follow-up, and no significant differences in white matter sparing were observed at study completion. These findings indicate that although SR9009 reduces acute activation of some secondary injury cascades, it does not promote long-term tissue preservation or functional recovery after contusive SCI in mice.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138443"},"PeriodicalIF":2.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513441","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

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。

{"title":"Short-term immobilization impairs pointing direction programming and early motor control processes","authors":"C.R. Scotto, F.R. Danion, Y. Blandin, L. Toussaint","doi":"10.1016/j.neulet.2025.138446","DOIUrl":"10.1016/j.neulet.2025.138446","url":null,"abstract":"<div><div>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 <em>direction</em>. 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 <em>Control</em> and <em>Immobilized</em> 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 <em>Immobilized</em> group and persisted until the uncorrected movement offset. These results suggest that immobilization impacts <em>direction</em> 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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138446"},"PeriodicalIF":2.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513406","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

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。

{"title":"Expression of serotonin transporter (SERT) and receptors 5-HTR1A and 5-HTR2A in an animal model of hypothermia","authors":"Andrei Negoiţă , Bogdan Amuzescu , Dan Florin Mihăilescu , Daniel Dumitru Banciu , Adela Banciu","doi":"10.1016/j.neulet.2025.138448","DOIUrl":"10.1016/j.neulet.2025.138448","url":null,"abstract":"<div><div>The role of anterior hypothalamus and preoptic area in thermoregulation has been studied since the late 19<sup>th</sup> 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 <em>t</em> 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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138448"},"PeriodicalIF":2.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513367","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

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。

{"title":"Immunohistochemically-detected differential localization of CXCL14 in mouse cerebellum suggesting the presence of neuronal and glial forms of CXCL14","authors":"Hirohumi Suzuki , Toshiharu Yamamoto , Aya Hasegawa , Toru Tamaki , Jun-ya Komagata , Takayoshi Yamaga , Tetsu Akasaka , Ryu-ichiro Hata","doi":"10.1016/j.neulet.2025.138442","DOIUrl":"10.1016/j.neulet.2025.138442","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138442"},"PeriodicalIF":2.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482640","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

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。

{"title":"Involvement of CXCR2 in chronic postsurgical pain occurrence through ERK/p38 activation","authors":"TianYu Ge , Xi Chen , Chang Liu , SaiSai Huang","doi":"10.1016/j.neulet.2025.138440","DOIUrl":"10.1016/j.neulet.2025.138440","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"870 ","pages":"Article 138440"},"PeriodicalIF":2.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452462","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

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