Neuroscience Letters最新文献_第8页

The dysregulation of high glucose-induced iPSC-neural stem cells differentiation by caspase-1. caspase-1对高糖诱导的ipsc -神经干细胞分化的失调。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-14 Epub Date: 2025-08-08 DOI: 10.1016/j.neulet.2025.138347

Hsien-Hui Chung

Maternal diabetes (MD) increases the risk for neurodevelopmental disorders and leads to neural tube defects (NTDs) which are severe anomalies of the nervous system. In order to elucidate the etiology and pathological mechanisms causing NTDs in MD and try to search for new therapeutic strategies as well, the exposure of induced pluripotency stem cell (iPSC)-neural stem cells (NSCs) to high glucose (HG) may be associated with fetal progressive deterioration of neuronal functions in utero ultimately leading to MD-related NTDs. In the present study, although HG (25 mM) had no effect on the viability of undifferentiated iPSC-NSCs compared with the positive control mannitol (25 mM), HG attenuated iPSC-NSCs cell proliferation and induced the presence of decreased βIII-tubulin and neurite network length during 7-day neuronal differentiation, resulting in the inability of nerve-to-nerve connections to communicate effectively. Compared with mannitol, HG actually reduced gene and protein expressions of iPSC-NSCs differentiation marker βIII-tubulin on day 7. Moreover, HG increased protein expressions of caspase-1 during 7-day neuronal differentiation compared with mannitol, indicating the critical role of caspase-1 in HG-mediated neuronal inflammation. Thus, the present study indicated that HG-induced impairment in iPSC-NSCs differentiation was mediated by decreased βIII-tubulin, shorter neurite network length and increased caspase-1 expressions, which provided a direction for the clarification of MD-induced NTDs.

产妇糖尿病（MD）增加了神经发育障碍的风险，并导致神经管缺陷（NTDs），这是神经系统的严重异常。为了阐明MD中NTDs的病因和病理机制，并试图寻找新的治疗策略，诱导多能干细胞(iPSC)-神经干细胞（NSCs）暴露于高糖（HG）可能与胎儿在子宫内神经元功能的进行性恶化有关，最终导致MD相关的NTDs。在本研究中，虽然HG（25 mM）与阳性对照甘露醇（25 mM）相比，对未分化iPSC-NSCs的活力没有影响，但在7天的神经元分化过程中，HG减弱了iPSC-NSCs细胞的增殖，诱导β iii -微管蛋白和神经突网络长度的减少，导致神经间连接无法有效沟通。与甘露醇相比，HG在第7天实际上降低了iPSC-NSCs分化标志物β iii -微管蛋白的基因和蛋白表达。此外，与甘露醇相比，HG在7天的神经元分化过程中增加了caspase-1的蛋白表达，这表明caspase-1在HG介导的神经元炎症中起着关键作用。因此，本研究表明，hg诱导的iPSC-NSCs分化障碍是通过β iii -微管蛋白减少、神经突网络长度缩短和caspase-1表达增加介导的，这为阐明md诱导的NTDs提供了方向。

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引用次数: 0

Ferulic acid possesses anxiolytic activity: evidence for the involvement of serotonergic and noradrenergic systems 阿魏酸具有抗焦虑活性：证据涉及血清素能和去甲肾上腺素能系统。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-12 DOI: 10.1016/j.neulet.2025.138416

Ozlem Pınar Cetiner , Hazal Eken , Feyza Alyu Altınok , Rana Arslan , Nurcan Bektas

The current study aims to evaluate any potential anxiolytic effects and the action mechanisms of ferulic acid, a phenolic phytochemical compound, in mice. The anxiolytic activity of ferulic acid at the doses of 0.1, 1, 10, and 100 mg/kg, p.o in female BALB/c mice was assessed by open field, hole-board and elevated plus maze tests. The possible roles of noradrenergic, serotonergic, and GABAergic modulation in the anxiolytic action of 100 mg/kg ferulic acid were also investigated by pretreatment with 5 mg/kg (i.p.) yohimbine, 1 mg/kg (i.p.) WAY-100635, and 3 mg/kg (i.p.) flumazenil, respectively, in the hole-board and open field tests. Similar to the positive standard diazepam (1 mg/kg, i.p); without altering the locomotor activity, 100 mg/kg ferulic acid significantly altered all the parameters related to anxiolytic activity, whereas 0.1 and 10 mg/kg doses were found to be effective in only some parameters in elevated plus-maze and open field tests, suggesting a U-shaped dose–response pattern. The anxiolytic effect of 100 mg/kg ferulic acid was significantly antagonized by the pretreatment with 5-HT_1A receptor antagonist WAY-100635 and especially by α-2 adrenoceptor antagonist yohimbine while the anxiolytic action was not blocked by GABA_A/BZ receptor antagonist flumazenil pretreatment. The findings imply that ferulic acid’s anxiolytic effect is mediated by the activation of α-2 adrenoceptors and 5-HT_1A receptors. In conclusion, it is possible to say that ferulic acid can be a safe potential agent which that be used alone or in combination with current effective treatments for anxiety.

本研究旨在评价阿魏酸（一种酚类植物化合物）对小鼠的潜在抗焦虑作用及其作用机制。采用开场、孔板、升高加迷宫试验，评价0.1、1、10、100 mg/kg, p.o剂量阿魏酸对BALB/c雌性小鼠的抗焦虑活性。用5 mg/kg （i.p.）育亨宾和1 mg/kg （i.p.）预处理阿魏酸，探讨去甲肾上腺素能、血清素能和gaba能调节在100 mg/kg阿魏酸抗焦虑作用中的可能作用。WAY-100635和3 mg/kg （i.p.）氟马西尼，分别在孔板试验和露天试验中。与阳性标准地西泮相似（1 mg/kg, i.p）；在不改变运动活性的情况下，100 mg/kg阿威酸显著改变了与焦虑活性相关的所有参数，而0.1和10 mg/kg阿威酸仅对部分参数有效，提示u型剂量-反应模式。100 mg/kg阿魏酸的抗焦虑作用可被5-HT1A受体拮抗剂WAY-100635和α-2肾上腺素受体拮抗剂育亨宾显著拮抗，而GABAA/BZ受体拮抗剂氟马西尼不阻断其抗焦虑作用。提示阿魏酸的抗焦虑作用是通过激活α-2肾上腺素受体和5-HT1A受体介导的。总之，可以说阿魏酸是一种安全的潜在药物，可以单独使用，也可以与目前有效的治疗焦虑症的药物联合使用。

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引用次数: 0

The role of BDNF/PI3K/AKT/Nrf2 signaling in nicotine’s protective effects against MPTP-induced Parkinson’s disease BDNF/PI3K/AKT/Nrf2信号在尼古丁对mptp诱导的帕金森病的保护作用中的作用

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-10 DOI: 10.1016/j.neulet.2025.138412

Nikoloz Zhgenti , Ekaterine Bakuradze , Otar Bibilashvili , Nana Koshoridze

Parkinson’s disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra, where oxidative stress and apoptosis play central roles. Epidemiological evidence suggests that nicotine may exert neuroprotective effects, but the molecular mechanisms remain incompletely understood. This study investigated whether nicotine mitigates MPTP-induced neurotoxicity in mice through modulation of the BDNF/PI3K/AKT/Nrf2 signaling pathway.

Male BALB/c mice were divided into control, nicotine, MPTP, and MPTP + nicotine groups. Histological analysis revealed that nicotine significantly reduced MPTP-induced neuronal pyknosis and preserved tyrosine hydroxylase-positive dopaminergic neurons. Biochemical assays showed that nicotine attenuated MPTP-induced increases in malondialdehyde, lactate dehydrogenase, and lactate/pyruvate ratio, while restoring complex I activity and antioxidant enzyme activities (SOD, CAT, GPx, GR). Western blotting demonstrated that nicotine reversed MPTP-induced suppression of phosphorylated PI3K, AKT, and Nrf2, and shifted apoptotic signaling toward survival by increasing Bcl-2 and reducing Bax and Bad.

Importantly, nicotine restored BDNF levels in the substantia nigra, and ex vivo experiments confirmed that nicotine upregulated BDNF via α7 nicotinic acetylcholine receptor activation. These findings suggest that nicotine confers neuroprotection by enhancing BDNF-mediated activation of the PI3K/AKT/Nrf2 axis, leading to improved antioxidant defenses and anti-apoptotic signaling.

In conclusion, nicotine mitigates MPTP-induced dopaminergic neurodegeneration via BDNF/PI3K/AKT/Nrf2 signaling. While nicotine’s addictive properties limit its therapeutic use, selective targeting of nicotinic pathways may represent a promising strategy for disease-modifying interventions in PD.

帕金森病（PD）的特征是黑质中多巴胺能神经元的进行性丧失，氧化应激和细胞凋亡在其中起核心作用。流行病学证据表明，尼古丁可能具有神经保护作用，但其分子机制仍不完全清楚。本研究探讨尼古丁是否通过调节BDNF/PI3K/AKT/Nrf2信号通路减轻MPTP诱导的小鼠神经毒性。将雄性BALB/c小鼠分为对照组、尼古丁组、MPTP组和MPTP + 尼古丁组。组织学分析显示，尼古丁可显著减少mptp诱导的神经元固缩，保存酪氨酸羟化酶阳性多巴胺能神经元。生化实验表明，尼古丁能减弱mptp诱导的丙二醛、乳酸脱氢酶和乳酸/丙酮酸比值的升高，同时恢复复合体I活性和抗氧化酶（SOD、CAT、GPx、GR）活性。Western blotting表明，尼古丁逆转了mptp诱导的磷酸化PI3K、AKT和Nrf2的抑制，并通过增加Bcl-2和降低Bax和Bad将凋亡信号转向存活。重要的是，尼古丁恢复了黑质中BDNF的水平，离体实验证实尼古丁通过α7烟碱乙酰胆碱受体激活上调BDNF。这些发现表明，尼古丁通过增强bdnf介导的PI3K/AKT/Nrf2轴的激活，从而增强抗氧化防御和抗凋亡信号传导，从而赋予神经保护作用。综上所述，尼古丁通过BDNF/PI3K/AKT/Nrf2信号通路减轻mptp诱导的多巴胺能神经变性。虽然尼古丁的成瘾性限制了其治疗用途，但选择性靶向尼古丁通路可能是PD疾病改善干预的一种有希望的策略。

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引用次数: 0

Differential expression of TRPV1 and TRPM8 in the mouse trigeminal ganglion and spinal dorsal root ganglion TRPV1和TRPM8在小鼠三叉神经节和脊髓背根神经节中的差异表达。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-10 DOI: 10.1016/j.neulet.2025.138413

Caifeng Shao , Jichao Wei , Hong-Yi Jia , Yu-Han Zhou , Mingwei Zhao , Kun Yang , Ming-Ming Zhang

Transient receptor potential (TRP) ion channels, including the thermoreceptor TRP vanilloid 1 (TRPV1) and innocuous warm detector TRP melastatin 8 (TRPM8), are widely expressed on the primary sensory neurons of the trigeminal ganglion (TG) and the dorsal root ganglion (DRG). By performing real-time quantitative PCR and immunostaining, we compared TRPV1 and TRPM8 gene expression and immunostaining in mouse DRG and TG neurons. Both TRPV1 and TRPM8 are widely expressed in the TG and DRG, but in different patterns: TRPV1 has relatively more abundant expression and immunostaining in the DRG, whereas TRPM8 has higher levels in the TG. Double-staining for TRPV1 and TRPM8 revealed very little coexpression in either the TG or the DRG. These results suggest that TRPV1 and TRPM8 are differentially expressed in TG and DRG, and this significant variation may underlie the different temperature sensory properties of the skin and oral cavity.

瞬时受体电位（TRP）离子通道在三叉神经节（TG）和背根神经节（DRG）的初级感觉神经元上广泛表达，包括热感受器TRP vanilloid 1 （TRPV1）和无害的热感受器TRP melastatin 8 （TRPM8）。通过实时定量PCR和免疫染色，我们比较了TRPV1和TRPM8基因在小鼠DRG和TG神经元中的表达和免疫染色。TRPV1和TRPM8均在TG和DRG中广泛表达，但表达模式不同：TRPV1在DRG中表达和免疫染色相对更丰富，而TRPM8在TG中表达水平更高。TRPV1和TRPM8的双染色在TG和DRG中均很少共表达。这些结果表明，TRPV1和TRPM8在TG和DRG中的表达存在差异，这种显著的差异可能是皮肤和口腔不同温度感觉特性的基础。

引用次数: 0

Insulin-regulated aminopeptidase inhibitor C9 restores cellular activity in methadone-damaged primary cell cultures 胰岛素调节的氨基肽酶抑制剂C9在美沙酮损伤的原代细胞培养中恢复细胞活性。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-10 DOI: 10.1016/j.neulet.2025.138415

Frida Stam , Sara Bjurling , Erik Nylander , Esther Olaniran Håkansson , Johan Gising , Mats Larhed , Luke R. Odell , Alfhild Grönbladh , Mathias Hallberg

Insulin-regulated aminopeptidase (IRAP) is emerging as a pharmaceutical target for treatment of neurotoxic- and neurodegenerative symptoms commonly seen in cognitive impairments. Ligands of IRAP, such as Angiotensin IV and similar analogues, bind to the active site of IRAP and causes an inhibition of its enzymatic activity, which is suggested to improve cognitive functions. Opioids are widely used in the clinic to treat for example pain and opioid use disorder, however opioid use have been associated with cognitive impairments, impaired neuronal development, and neuronal damage. To evaluate the potential of the macrocyclic IRAP inhibitor compound 9 (C9), the present study examined the restorative effects of C9 after opioid-induced cell toxicity. The toxic impact of the commonly used opioids methadone and buprenorphine was determined in rat primary hippocampal and cortical cells, along with the effects on various viability markers after subsequent treatment with C9. The metabolism of tetrazolium bromide salt (MTT) was measured to assess mitochondrial activity, and the level of membrane damage was assessed by measuring lactate dehydrogenase (LDH) in the cell media. Fluorescent calcein dye was used to evaluate intracellular esterase activity. In conclusion, this study demonstrate that methadone and buprenorphine induce toxic effects in primary hippocampal and cortical cell cultures and that IRAP inhibitor C9 has a restorative effect on intracellular esterase activity in methadone-damaged cells.

胰岛素调节氨基肽酶（IRAP）正在成为治疗认知障碍中常见的神经毒性和神经退行性症状的药物靶点。IRAP的配体，如血管紧张素IV和类似的类似物，结合到IRAP的活性位点并抑制其酶活性，这被认为可以改善认知功能。阿片类药物在临床上被广泛用于治疗疼痛和阿片类药物使用障碍，然而阿片类药物的使用与认知障碍、神经元发育受损和神经元损伤有关。为了评估大环IRAP抑制剂化合物9 （C9）的潜力，本研究检测了C9在阿片类药物诱导的细胞毒性后的恢复作用。研究了常用阿片类药物美沙酮和丁丙诺啡对大鼠海马和皮质细胞的毒性作用，以及C9后续治疗对各种活力指标的影响。通过测定四氮唑溴化盐（MTT）代谢来评估线粒体活性，通过测定细胞培养基中的乳酸脱氢酶（LDH）来评估膜损伤水平。荧光钙黄蛋白染色法测定细胞内酯酶活性。总之，本研究表明，美沙酮和丁丙诺啡在原代海马和皮质细胞培养中诱导毒性作用，并且IRAP抑制剂C9对美沙酮损伤细胞的细胞内酯酶活性具有恢复作用。

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引用次数: 0

Stable Traits, Adaptive Brains: links between Visual Homeostatic Plasticity and Personality 稳定特征，适应性大脑：视觉稳态可塑性与个性之间的联系。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-10 DOI: 10.1016/j.neulet.2025.138414

Marina Baroni , Valentina Cesari , Angelo Gemignani , Maria Concetta Morrone , Claudia Lunghi , Danilo Menicucci

This study explores the relationship between personality traits and visual homeostatic plasticity, a neural mechanism maintaining stable the brain activity. Actually, personality may influence neuroplasticity, the general brain ability to adapt through experiences. Indeed, prior research links traits like openness to experience and neuroticism to Hebbian plasticity (experience-based synaptic strengthening), but any connections to homeostatic plasticity remain largely unexplored.

To probe homeostatic plasticity we tested the effect of short-term monocular deprivation in 24 healthy adults. Participants wore an eye patch for two hours, and underwent binocular rivalry tests measuring shifts in perceptual dominance. The deprivation index, reflecting homeostatic plasticity in the primary visual cortex, was analysed alongside personality traits assessed via the Big Five Questionnaire.

Results revealed a positive correlation between the deprivation index and conscientiousness but a negative correlation with emotional stability. Conscientious individuals, often goal-directed and self-regulated, showed reduced homeostatic plasticity, suggesting diminished mental flexibility. Conversely, higher emotional stability (lower neuroticism) enhanced homeostatic plasticity, aligning with findings that neuroticism reduces resilience, a potential link to impaired plasticity.

Overall, the study suggests that homeostatic plasticity, often limited to sensory adaptation, might reflect broader brain regulatory properties that appear to be linked to personality traits.

本研究探讨了人格特质与视觉稳态可塑性（一种维持大脑活动稳定的神经机制）之间的关系。实际上，性格可能会影响神经可塑性，即大脑通过经历适应的能力。事实上，先前的研究将经验开放性和神经质等特征与Hebbian可塑性（基于经验的突触强化）联系起来，但任何与稳态可塑性的联系在很大程度上仍未被探索。为了探究体内平衡的可塑性，我们对24名健康成人进行了短期单眼剥夺的实验。参与者戴上眼罩两个小时，进行双眼竞争测试，测量感知优势的变化。剥夺指数反映了初级视觉皮层的自我平衡可塑性，并通过大五问卷对人格特征进行了评估。结果表明，剥夺指数与责任心呈正相关，与情绪稳定性呈负相关。有责任心的人，往往以目标为导向，自我调节，表现出较低的内稳态可塑性，表明心理灵活性下降。相反，较高的情绪稳定性（较低的神经质）增强了体内平衡的可塑性，这与神经质降低弹性的研究结果一致，这是与可塑性受损的潜在联系。总的来说，这项研究表明，通常局限于感觉适应的内稳态可塑性可能反映了更广泛的大脑调节特性，这些特性似乎与人格特征有关。

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引用次数: 0

Mitochondrial dysfunction and aging can be alleviated by modulating calcineurin and cardiolipin dynamics following stroke 脑卒中后可通过调节钙调磷酸酶和心磷脂动态来缓解线粒体功能障碍和衰老。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-06 DOI: 10.1016/j.neulet.2025.138410

Pallab Bhattacharya , Shailendra Saraf , Anirban Barik , Bijoyani Ghosh , Aishika Datta , Davendra Singh Malik

The crucial influence of mitochondria in ischemic stroke pathophysiology presents many unexplored yet promising avenues for therapeutic strategies and clinical outcomes. Post-stroke mitochondrial dysfunction contributes to aggravated levels of calcium overload and apoptosis. This dysfunction is signified by disruption of the mitochondrial lipids such as cardiolipin, along with mitochondrial DNA mutation, leading to an imbalance in mitophagy. Calcium overload-mediated calcineurin overexpression has been reported to exacerbate mitochondrial damage and further contribute to neuronal apoptosis. In our study, we explored the alterations in the mitochondrial function following inhibition of the calcium-mediated calcineurin levels in post-stroke condition. In a rodent model of middle cerebral artery occlusion (MCAo), we observed that the inhibition of the calcium channels in post-stroke condition led to restored neuronal histology and viability following upregulation of the antioxidant levels. At the mitochondrial level, calcium channel inhibition downregulated calcineurin activation and normalized cardiolipin concentration, mitochondrial membrane potential, and respiratory control ratio in post-stroke condition. This inhibition also balanced the mitochondrial dynamics proteins and mitophagy towards neuronal recovery following ischemic stress. Moreover, it also normalized the expression of TERT, a key marker of mitochondrial health and aging. These findings highlight the role of calcium-mediated calcineurin in influencing mitochondrial dysfunction and aging in ischemic stroke. Thus, calcium channel inhibition offers a promising therapeutic strategy by preserving mitochondrial integrity and promoting neuroprotection following stroke.

线粒体在缺血性卒中病理生理中的重要影响为治疗策略和临床结果提供了许多尚未探索但有希望的途径。脑卒中后线粒体功能障碍导致钙超载和细胞凋亡水平加重。这种功能障碍表现为线粒体脂质（如心磷脂）的破坏，以及线粒体DNA突变，导致线粒体自噬失衡。据报道，钙超载介导的钙调磷酸酶过表达会加剧线粒体损伤，并进一步导致神经元凋亡。在我们的研究中，我们探讨了脑卒中后钙介导的钙调磷酸酶水平被抑制后线粒体功能的变化。在大脑中动脉闭塞（MCAo）的啮齿动物模型中，我们观察到脑卒中后钙通道的抑制导致抗氧化剂水平上调后神经元组织学和活力的恢复。在线粒体水平上，钙通道抑制可下调脑卒中后钙调磷酸酶的激活，使心磷脂浓度、线粒体膜电位和呼吸控制率正常化。这种抑制也平衡了线粒体动力学蛋白和线粒体自噬对缺血应激后神经元恢复的影响。此外，它还使TERT的表达正常化，TERT是线粒体健康和衰老的关键标志。这些发现强调了钙介导的钙调神经磷酸酶在影响缺血性卒中线粒体功能障碍和衰老中的作用。因此，钙通道抑制提供了一个有希望的治疗策略，通过保持线粒体完整性和促进中风后的神经保护。

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引用次数: 0

Regional differences in oxytocin and vasopressin 1a receptor functionality in mouse embryonic brain development 小鼠胚胎脑发育中催产素和抗利尿激素1a受体功能的区域差异。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-05 DOI: 10.1016/j.neulet.2025.138409

Elliot Sommer , Heather K. Caldwell

There is mounting evidence that the oxytocin (Oxt) and vasopressin (Avp) systems contribute to early brain development. Work from transgenic mouse models as well as pharmacological manipulation of the Oxt and Avp systems suggests that signaling through the Oxt receptor (Oxtr) and the Avp 1a receptor (Avpr1a) during embryonic brain development affects behavior in adulthood. Unfortunately, at this time, very little is known or understood about where in the brain Oxtr and Avpr1a occurs during embryonic development or what the downstream consequences may be. To help provide some answers, Oxtr- and Avpr1a-stimulated G-protein coupled receptor binding assays were performed using guanosine 5′-(γ-thio)triphosphate, a non-hydrolyzable analog of guanosine triphosphate, to determine the functionality of the Oxtr and Avpr1a in both sexes at embryonic day (E) 14.5, E16.5, and E18.5. Based on previous work, we hypothesized that the Oxtr and Avpr1a would be functional in both sexes by E16.5 and activated by Oxt and Avp, respectively. The data suggest that while the Oxtr and Avpr1a are functional in both sexes starting at E16.5, where in the brain they are functional is not fully aligned with where there is known receptor binding. For the Oxtr, at E16.5, functional binding was observed in the ventricular and subventricular zones of the cortical and septal neuroepithelium and the amygdalar area, this shifted by E18.5 with functional binding observed only in the ventricular and subventricular septal neuroepithelium and the amygdalar area, with no functional binding observed in the ventricular and subventricular cortical neuroepithelium. For the Avpr1a, at E16.5, functional binding was only observed in the ventral hypothalamic area but by E18.5 functional binding was observed across numerous brain regions. Taken together, these data suggest that Oxtr and Avpr1a signaling is positioned to have site-specific effects on mouse brain development starting at E16.5.

越来越多的证据表明，催产素（Oxt）和抗利尿激素（Avp）系统有助于早期大脑发育。转基因小鼠模型以及对Oxt和Avp系统的药理学操作表明，在胚胎大脑发育过程中，通过Oxt受体（Oxtr）和Avp 1a受体（Avpr1a）传递的信号会影响成年期的行为。不幸的是，目前对于Oxtr和Avpr1a在胚胎发育过程中发生在大脑的哪个位置以及可能的下游后果知之甚少。为了提供一些答案，使用鸟苷5'-（γ-硫）三磷酸（鸟苷三磷酸的不可水解类似物）进行了Oxtr和Avpr1a刺激的g蛋白偶联受体结合测定，以确定Oxtr和Avpr1a在胚胎日(E) 14.5, E16.5和E18.5两性中的功能。基于之前的工作，我们假设Oxtr和Avpr1a在两性中通过E16.5发挥功能，并分别被Oxt和Avp激活。这些数据表明，虽然Oxtr和Avpr1a从E16.5岁开始在两性中都有功能，但它们在大脑中的功能位置与已知受体结合的位置并不完全一致。对于Oxtr，在E16.5时，在脑室和脑室下区皮层和间隔神经上皮以及杏仁核区观察到功能结合，到E18.5时，这种情况发生了变化，仅在脑室和室间隔下神经上皮以及杏仁核区观察到功能结合，在脑室和脑室下皮层神经上皮未观察到功能结合。对于Avpr1a，在E16.5时，仅在下丘脑腹侧区域观察到功能结合，但在E18.5时，在许多脑区观察到功能结合。综上所述，这些数据表明Oxtr和Avpr1a信号在E16.5开始对小鼠大脑发育具有位点特异性影响。

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引用次数: 0

Increased reactive oxygen species in the spinal cord drive renal sympathetic vasomotor activity in Goldblatt hypertensive rats Goldblatt高血压大鼠脊髓活性氧增加驱动肾交感血管舒张活性。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-03 DOI: 10.1016/j.neulet.2025.138408

Fernanda M. Tagliapietra, Maycon I.O. Milanez, Edina da Luz Abreu, Erika E. Nishi, Cássia T. Bergamaschi, Ruy R. Campos

Increased production of reactive oxygen species (ROS) in brain regions contributes to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Previously, studies reported that overexpression of spinal angiotensin II (Ang II) type I (AT1) contributes to sympathetic vasomotor overactivation in 2K1C rats. Considering that Ang II leads to an imbalance of oxidative stress, the present study evaluated the role of spinal ROS in regulating the activity of sympathetic preganglionic neurons in 2K1C rats. Hypertension was induced by clipping the left renal artery. Six weeks after clipping, a catheter was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of intrathecal (i.t.) injection of Tempol on mean arterial pressure (MAP), heart rate (HR), renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated over 60 consecutive minutes. mRNA expression of enzymes involved in oxidative balance was analyzed in the spinal cord. In addition, spinal ROS abundance was quantified by the DHE fluorescence method. An increase in ROS production was observed in the thoracic region of 2K1C rats compared to the control group. I.t. administration of Tempol triggered a significant and preferential reduction in rSNA in the 2K1C but not in control rats. Thus, the data suggest that renal sympathoexcitation in 2K1C rats was associated with an increase in oxidative imbalance in the spinal cord, particularly in sympathetic preganglionic neurons that drive rSNA.

脑区活性氧（ROS）的产生增加有助于Goldblatt高血压（2K1C）交感血管舒动过度活跃。先前的研究报道，脊髓血管紧张素II (Ang II) I型（AT1）的过度表达有助于2K1C大鼠交感血管舒缩过度激活。考虑到Ang II导致氧化应激失衡，本研究评估了脊髓ROS在调节2K1C大鼠交感神经节前神经元活性中的作用。左肾动脉夹持引起高血压。夹持6周后，将导管插入蛛网膜下腔并推进至尿道麻醉大鼠的T10-11椎体水平。观察连续60分钟鞘内注射Tempol对大鼠平均动脉压（MAP）、心率（HR）、肾脏和内脏交感神经活动（rSNA和sSNA）的影响。分析脊髓中参与氧化平衡的酶的mRNA表达。此外，用DHE荧光法定量脊髓ROS丰度。与对照组相比，在2K1C大鼠的胸部区域观察到ROS的产生增加。Tempol在2K1C大鼠中触发了显著的、优先的rSNA减少，但在对照大鼠中没有。因此，这些数据表明，2K1C大鼠的肾交感神经兴奋与脊髓氧化不平衡的增加有关，特别是在驱动rSNA的交感神经节前神经元中。

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引用次数: 0

Combined chronic oral methylphenidate and fluoxetine treatment increases CB1 receptor density in the somatosensory forelimb region 慢性口服哌甲酯和氟西汀联合治疗可增加躯体感觉前肢区域CB1受体密度。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-10-02 DOI: 10.1016/j.neulet.2025.138407

Abigail M. Lantry , Huy Lu , Matt Marion , John Hamilton , Brittany Richardson , Teresa Quattrin , Lucy D. Mastrandrea , Michael Hadjiargyrou , David Komatsu , Panayotis K. Thanos

Methylphenidate (MP) is a psychostimulant commonly prescribed for attention-deficit/hyperactivity disorder (ADHD), and Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to treat depression and anxiety disorders. Both are shown to impact neurochemistry and behavior, but little is known about their individual and combined impacts on the endocannabinoid system (ECS). We examined the effects of MP and FLX, both as separate treatments and in combination, on cannabinoid receptor type 1 (CB1) binding in several key brain regions of interest. Male rats were treated with either water, MP, FLX, or MP + FLX via a previously established drinking paradigm for three months. Brains were harvested, and [³H] SR141716A in vitro autoradiography was performed to quantify CB1 binding. The combined treatment of MP + FLX showed significantly higher [³H] SR141716A binding compared to the water, MP, and FLX groups in the somatosensory forelimb (S(FL)) region. This indicates an ability of the common co-usage of MP and FLX to increase CB1 levels in the somatosensory cortex: a region of the brain required for the processing of sensory information.

哌醋甲酯（MP）是一种精神兴奋剂，通常用于治疗注意力缺陷多动障碍（ADHD），氟西汀（FLX）是一种血清素选择性再摄取抑制剂（SSRI），通常用于治疗抑郁症和焦虑症。两者都被证明会影响神经化学和行为，但对它们对内源性大麻素系统（ECS）的单独和联合影响知之甚少。我们研究了MP和FLX的作用，无论是单独治疗还是联合治疗，对大麻素受体1型（CB1）在几个关键脑区结合的影响。雄性大鼠分别用水、MP、FLX或MP + FLX通过先前建立的饮用模式治疗三个月。采集脑，对[3H] SR141716A进行体外放射自显影以定量CB1结合。与水、MP和FLX组相比，MP + FLX联合处理在体感觉前肢S（FL）区显示出更高的[3H] SR141716A结合。这表明MP和FLX的共同使用能够增加体感觉皮层（大脑中处理感觉信息所需的区域）中CB1的水平。

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