Neuroscience Letters最新文献_第9页

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 : 2025-11-20 Epub 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 : 2025-11-20 Epub 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

Dexmedetomidine improves postoperative cognitive dysfunction via regulating Adrb2/Pkg 右美托咪定通过调节Adrb2/Pkg改善术后认知功能障碍：右美托咪定抗术后认知功能障碍。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-20 Epub Date: 2025-10-01 DOI: 10.1016/j.neulet.2025.138406

Cuirong Chen , Hong Han , Hongzhe Li , Zitan Zhang , Yingbing Lv

Background

Postoperative cognitive dysfunction (POCD) refers to postoperative neurological complications in patients, thus affecting patients’ normal daily life.

Purpose

Our study aimed to confirm whether Adrb2/Pkg are involved in the protective effect of Dexmedetomidine (Dex) against POCD in rats.

Methods

The targets for Dex against POCD were screened by online databases. An POCD rat model was constructed, and the Morris water maze tests were conducted to evaluate the cognitive function of POCD rats. The inflammatory markers (IL-6, TNF-α, and IL-13) were recorded, and the levels of Adrb2 and Pkg in hippocampus tissue were detected using RT-qPCR. The key targets Adrb2/Pkg were verified through the LPS-induced inflammatory BV-2 cell model.

Results

Network pharmacology analysis predicted that Adrb2 and Pkg were the key genes of Dex against POCD. Dex treatment improved learning and memory skills of POCD rats. In vitro and in vivo experiments showed that Dex treatment alleviated inflammation, and upregulated Adrb2 and Pkg mRNA levels of POCD rats and inflammatory BV-2 cell line. Silencing Adrb2/Pkg reversed the apoptosis suppression in LPS-induced inflammatory BV-2 cells caused by Dex.

Conclusion

The Adrb2/Pkg could potentially be the mechanism by which Dex protects POCD rats from cognitive impairment.

背景：术后认知功能障碍（POCD）是指患者术后出现的神经系统并发症，从而影响患者的正常生活。目的：研究Adrb2/Pkg是否参与右美托咪定（Dex）对大鼠POCD的保护作用。方法：利用在线数据库筛选Dex抗POCD的靶点。建立POCD大鼠模型，采用Morris水迷宫实验评价POCD大鼠的认知功能。记录炎症标志物（IL-6、TNF-α、IL-13）， RT-qPCR检测海马组织Adrb2、Pkg水平。通过lps诱导的炎症BV-2细胞模型验证关键靶点Adrb2/Pkg。结果：网络药理学分析预测Adrb2和Pkg是右美托明斯抗POCD的关键基因。右美托咪唑治疗可提高POCD大鼠的学习记忆能力。体外和体内实验表明，右美托明能减轻POCD大鼠的炎症反应，上调POCD大鼠及炎症BV-2细胞系Adrb2和Pkg mRNA水平。Adrb2/Pkg的沉默逆转了Dex引起的脂多糖诱导的炎症BV-2细胞的凋亡抑制。结论：Adrb2/Pkg可能是Dex保护POCD大鼠认知功能障碍的机制。

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引用次数: 0

Hydrogen sulfide protects against hippocampal neuronal apoptosis in aged rats with postoperative cognitive dysfunction by promoting m6A methylation 硫化氢通过促进m6A甲基化对术后认知功能障碍老年大鼠海马神经元凋亡的保护作用。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-20 Epub Date: 2025-09-30 DOI: 10.1016/j.neulet.2025.138405

Bo Wang , YongPan Wen , Yonghong Tang , Min Li

Purpose

To explore the potential involvement of m6A methylation in the neuroprotective mechanism of H₂S against hippocampus neuronal apoptosis in aged rats with POCD.

Methods

Sprague-Dawley rats (18–20 months) were subjected to anesthesia and laparotomy surgery to establish an animal model of POCD. The Open Field, Y-maze, and Novel Object Recognition tests assessed behavioral performance. Protein expression levels were analyzed using Western blot analysis, and neuronal apoptosis was analyzed using TUNEL staining.

Results

NaHS (100 μmol/kg) significantly increased the alternation ratio of the Y-maze test and the discrimination index of the NOR test, reduced hippocampal neuronal apoptosis, indicated by decreased TUNEL-positive neurons and modulated the expression of apoptosis-related protein markers (Bcl-2 was upregulated and Bax/Cleaved caspase-3 were downregulated). Furthermore, NaHS restored reduced m⁶A RNA methylation levels and corrected the disturbed expression of m⁶A-related enzymes (METTL3, METTL14, YTHDF1, YTHDF3, FTO, ALKBH5) in the hippocampus of aged rats with POCD.

Conclusion

H₂S shows neuroprotective effects by mitigating hippocampal neuronal apoptosis and restoring m⁶A RNA methylation in the hippocampus of aged rats with POCD. These findings provide preclinical evidence that H₂S may serve as a potential therapeutic agent for the prevention of POCD.

目的：探讨m6A甲基化可能参与H2S对老年POCD大鼠海马神经元凋亡的神经保护机制。方法：采用Sprague-Dawley大鼠（18-20 月龄）麻醉并开腹手术建立POCD动物模型。开放领域、y形迷宫和新物体识别测试评估行为表现。Western blot分析蛋白表达水平，TUNEL染色分析神经元凋亡。结果：NaHS（100 μmol/kg）显著提高y迷宫试验的交替率和NOR试验的鉴别指数，减少海马神经元凋亡，表现为tunel阳性神经元减少，并调节凋亡相关蛋白标志物的表达（Bcl-2上调，Bax/Cleaved caspase-3下调）。此外，NaHS恢复了老年POCD大鼠海马中m6A RNA甲基化水平的降低，并纠正了m6A相关酶（METTL3、METTL14、YTHDF1、YTHDF3、FTO、ALKBH5）的紊乱表达。结论：H2S可减轻老年POCD大鼠海马神经元凋亡，恢复海马m6A RNA甲基化，具有神经保护作用。这些发现为H2S可能作为预防POCD的潜在治疗剂提供了临床前证据。

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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 : 2025-11-20 Epub 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

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 : 2025-11-20 Epub 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

GABAergic disinhibition through the STING-dependent autophagic pathway in the dorsal horn underlies diabetic neuropathic pain pathogenesis 糖尿病神经性疼痛的发病机制是通过背角中sting依赖的自噬途径解除gaba能抑制。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-20 Epub Date: 2025-09-28 DOI: 10.1016/j.neulet.2025.138391

Ya-Jie Zhao , Hong-Zhen Bai , Yi-Na Wang , Yu-Kun Liu , Long-Biao Zhao , Zhao Li , Hui-Zhou Li , Xiu-Li Wang , Peng Liu

Our previous study demonstrated that STING/ATG5-mediated autophagy in the spinal dorsal horn contributes to diabetic neuropathic pain (DNP), although the underlying mechanisms remained unclear. In this study, we investigated how STING-driven autophagy leads to impaired spinal inhibition via lysosomal degradation of GABA receptors. In a rat model of DNP, spinal levels of STING and ATG5 were elevated, while P62, GABA_A receptor, and GABA_B receptor expression were reduced. Behavioral tests showed that intrathecal administration of a STING inhibitor increased mechanical pain thresholds and upregulated P62 and GABA receptors. Conversely, treatment with a STING agonist worsened hyperalgesia and further suppressed GABA receptor expression. Knockdown of ATG5 via siRNA similarly alleviated pain and restored GABA receptor levels. Interestingly, although the mTOR inhibitor rapamycin alleviated neuropathic pain, it unexpectedly increased spinal P62 expression compared to the DNP group. Administration of leupeptin, a lysosomal protease inhibitor, significantly increased paw withdrawal thresholds on days 1–3 and elevated GABA receptor expression, whereas the proteasomal inhibitor MG132 had no effect. These results demonstrate that STING/ATG5-mediated autophagy promotes DNP through autophagic-lysosomal degradation of GABA receptors, highlighting this pathway as a promising therapeutic target for treating diabetic neuropathic pain.

我们之前的研究表明，脊髓背角中STING/ atg5介导的自噬有助于糖尿病神经性疼痛（DNP），尽管其潜在机制尚不清楚。在这项研究中，我们研究了sting驱动的自噬如何通过溶酶体降解GABA受体导致脊髓抑制受损。在DNP大鼠模型中，脊髓中STING和ATG5水平升高，而P62、GABAA 受体和GABAB 受体表达降低。行为学实验显示鞘内注射STING抑制剂增加了机械痛阈值，上调了P62和GABA受体。相反，使用STING激动剂治疗会加重痛觉过敏，并进一步抑制GABA受体的表达。通过siRNA敲低ATG5同样可以减轻疼痛并恢复GABA受体水平。有趣的是，尽管mTOR抑制剂雷帕霉素减轻了神经性疼痛，但与DNP组相比，它意外地增加了脊髓P62的表达。溶酶体蛋白酶抑制剂lepeptin可显著提高第1-3天的断爪阈值，并提高GABA受体的表达，而蛋白酶体抑制剂MG132则没有影响。这些结果表明，STING/ atg5介导的自噬通过自噬-溶酶体降解GABA受体来促进DNP，强调这一途径是治疗糖尿病神经性疼痛的有希望的治疗靶点。

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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 : 2025-11-20 Epub 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

Relationship between prefrontal oxygenation during task-set period and executive function in healthy older people: A near-infrared spectroscopy study 健康老年人任务设定期前额叶氧合与执行功能的关系：近红外光谱研究

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-20 Epub Date: 2025-09-27 DOI: 10.1016/j.neulet.2025.138395

Yumi Oboshi , Mitsuru Kikuchi , Yasuomi Ouchi

Introduction

In past research, we have examined the characteristics of brain activity caused by prefrontal task completion in healthy older adults in a simplified manner using a near-infrared spectroscopy device, with the aim of identifying methods of early intervention to prevent their cognitive decline. Previously, we reported that prefrontal oxygenation during pre-task preparation was greater in young adults than older adults, and that this greater activation was associated with better task performances in both groups. To extend this research, in the present study, we examined previous findings with task repetitions, as older adults take more time to become familiar new tasks.

Methods

We modified the working memory task with a clear task-set instruction and examined the change in the task-set and task-induced activation in 63 cognitively healthy older adults.

Results

Task-set activation did not increase even after three repetitions, and the task-induced activation was greater than task-set activation in most channels. The difference in degree between task-induced activation and task-set activation showed a reduction with task repetitions. Significant inverse correlations were observed between the prefrontal activation due to the task itself in the third session, i.e., after task repetitions and the reaction time of the Trail Making Test, which represents attentional function.

Discussion

These results indicate that continued activation by the task itself, which persists even after older adults become familiar with the task, may be associated with executive function decline.

在过去的研究中，我们使用近红外光谱设备以简化的方式检查了健康老年人前额叶任务完成引起的大脑活动特征，目的是确定早期干预方法，以防止他们的认知能力下降。在此之前，我们报道了年轻人在任务前准备过程中的前额叶氧合比老年人更大，并且这种更大的激活与两组更好的任务表现有关。为了扩展这项研究，在本研究中，我们对先前的研究结果进行了检查，因为老年人需要更多的时间来熟悉新任务。方法：采用明确的任务集指令修改工作记忆任务，观察63名认知健康老年人工作记忆任务集和任务诱发激活的变化。结果：三次重复后，任务集激活并未增加，且大多数通道的任务诱发激活大于任务集激活。任务诱发激活和任务集激活的程度差异随着任务的重复而减小。在第三阶段，即任务重复后，由任务本身引起的前额叶激活与代表注意功能的造径测试反应时间呈显著负相关。讨论：这些结果表明，任务本身的持续激活，即使在成年人熟悉任务后仍然存在，可能与执行功能下降有关。

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引用次数: 0

Dynamic current-clamp unveiling the indispensable interplay between Nav1.7 and Nav1.8 for shaping action potential trajectory and retaining neuroexcitation of visceral sensory neurons 动态电流钳揭示了Nav1.7和Nav1.8在形成动作电位轨迹和保持内脏感觉神经元神经兴奋方面不可或缺的相互作用。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-01 Epub Date: 2025-09-20 DOI: 10.1016/j.neulet.2025.138387

Ying Li , Chen Zhang , Limin Han , Zhao Qian

Tetrodotoxin (TTX)-sensitive/Nav1.7- and TTX-resistive/Nav1.8 Na⁺ channels contribute to neuroexcitation in the sensory neurons of the nodose ganglion (NG); however, their specific roles remain debatable. Therefore, we aimed to study the action potential (AP) elicited from NG neurons isolated from adult rats and simulated by a dynamic current clamp (DCC) using gNa0/Nav1.7 and/or gNa1/Nav1.8 injection. We trained and tuned the voltage-dependent profiles of the Na⁺ current generated from the DCC using the Hodgkin–Huxley/Vandenberg models to match the AP parameters elicited by a brief pulse. A- or C-type AP could be simulated using DCC by applying gNa0 or gNa0/gNa1 alongside reduced gNa0 to avoid overshooting the up-stroke. This indicates the indispensability of these two Na⁺ channels for shaping the AP trajectory with tight orchestration. The hump over the repolarization period featuring C-type neurons could be generated using DCC by adding gNa1 in this cellular model. Furthermore, both A- and C-type repeated discharges can be simulated using gNa0 or gNa1 with a reduced gNa0. Similar experiments were performed on human embryonic kidney 293 cells with stable Nav1.7 expression to mimic A-type-like conditions for further verification. Both A- and C-type-like APs were simulated in this expression system by adding gNa0 or gNa0/gNa1. Therefore, Nav1.7/Nav1.8 is crucial in shaping the AP trajectory, with specific timing for Nav1.8 activation to retain neuroexcitation in the sensory nervous system. Additionally, this pilot study will establish a fundamental base for the pharmacological screening of targeted ion channels and validate the disease-based mechanism in cardiology and neuroscience.

河豚毒素（TTX）敏感/Nav1.7-和TTX抵抗/Nav1.8 Na+通道参与结节神经节（NG）感觉神经元的神经兴奋；然而，它们的具体作用仍有争议。因此，我们旨在研究从成年大鼠分离的NG神经元引发的动作电位（AP），并使用gNa0/Nav1.7和/或gNa1/Nav1.8注射动态电流钳（DCC）模拟。我们使用霍奇金-赫胥黎/范登堡模型训练和调整了DCC产生的Na+电流的电压依赖谱，以匹配短脉冲引发的AP参数。A型或c型AP可以使用DCC模拟，通过施加gNa0或gNa0/gNa1以及减小的gNa0来避免上冲程过冲。这表明这两个Na+通道对于形成紧密编排的AP轨迹是不可或缺的。在细胞模型中加入gNa1后，DCC可以产生c型神经元复极期的驼峰。此外，A型和c型重复放电都可以用减小的gNa0或gNa1来模拟。在稳定表达Nav1.7的人胚胎肾293细胞上进行类似实验，模拟a型样条件，进一步验证。通过添加gNa0或gNa0/gNa1来模拟A型和c型ap。因此，Nav1.7/Nav1.8对于形成AP轨迹至关重要，通过特定的Nav1.8激活时间来保持感觉神经系统的神经兴奋。此外，本初步研究将为靶向离子通道的药理学筛选奠定基础，并在心脏病学和神经科学中验证基于疾病的机制。

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