Neuroscience Letters最新文献_第3页

Age-dependent increase in apoptosis is associated with dysregulation of miR-92a/Akt/mTOR and NF-κB signaling pathways in male rats 在雄性大鼠中，年龄依赖性的凋亡增加与miR-92a/Akt/mTOR和NF-κB信号通路的失调有关。

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138115

Roya Naderi , Rahil Salimi , Abbas Jafari , Nasrin Mehranfard

Brain aging is the leading risk factor for most neurodegenerative diseases and has been linked with high rates of neuron loss. Thus, identifying molecular mechanisms underlying neuron loss and pharmacological modulation may be of great importance for slowing or preventing age-related diseases. Herein, we investigated the roles of miR-92a, Akt, mTOR, and NF-κB in age-associated apoptosis in the hippocampus (a critical structure involved in brain aging) of male rats alone and in combination with prazosin. Twenty-four male Wistar rats were grouped into young control (3-month-old), aged (18-month-old), and aged + prazosin groups (n = 8 for each). Prazosin (1 mg/kg; i.p.) was administered for 4 weeks to aged rats. Apoptosis was detected by TUNEL staining. Western blot for Akt, mTOR, and NF-κB was conducted. miR-92a gene expression was performed by using RT-PCR. The results indicated a marked enhancement of apoptosis in the aging hippocampus. We also detected substantial up-regulation of NF-κB as well as substantial down-regulation of phosphorylated-Akt and mTOR in the aging hippocampus. Moreover, miR-92a gene expression was markedly reduced in the aging hippocampus. Treatment with prazosin significantly suppressed apoptosis and reversed miR-92a gene expression, as well as Akt, mTOR, and NF-κB protein expressions in the aging hippocampus. Considering the NF-κB regulatory role on miRNAs, our results suggest that NF-κB may be a negative transcriptional regulator of miR-92a, which in turn could regulate the Akt/mTOR signaling. In this regard, NF-κB upregulation may mediate the downregulation of miR-92a/Akt/mTOR axis, and thereby contribute to age-related neurodegeneration. This may provide a novel treatment target for delaying or preventing age-related problems.

脑老化是大多数神经退行性疾病的主要危险因素，并与神经元的高损失率有关。因此，确定神经元丢失和药理调节的分子机制对于减缓或预防与年龄相关的疾病可能非常重要。在此，我们研究了miR-92a、Akt、mTOR和NF-κB在雄性大鼠海马（参与脑衰老的关键结构）中与年龄相关的凋亡中的作用。24只雄性Wistar大鼠分为幼龄对照组（3月龄）、老年组（18月龄）和老年 + 哌唑嗪组（各 = 8只）。 哌唑嗪(1毫克/公斤;给老龄大鼠ig (i.p.) 4 周。TUNEL染色检测细胞凋亡。对Akt、mTOR、NF-κB进行Western blot检测。RT-PCR检测miR-92a基因表达。结果表明，衰老海马细胞凋亡明显增强。我们还检测到衰老海马中NF-κB的显著上调以及磷酸化akt和mTOR的显著下调。此外，miR-92a基因在衰老海马中的表达明显降低。prazosin显著抑制衰老海马细胞凋亡，逆转miR-92a基因表达以及Akt、mTOR、NF-κB蛋白表达。考虑到NF-κB对mirna的调控作用，我们的研究结果表明NF-κB可能是miR-92a的负转录调控因子，进而调控Akt/mTOR信号通路。因此，NF-κB上调可能介导miR-92a/Akt/mTOR轴下调，从而参与年龄相关性神经退行性变。这可能为延缓或预防与年龄有关的问题提供新的治疗靶点。

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引用次数: 0

Extracellular baskets in inner hair cells and perineuronal nets in auditory nerves: Changes in noise-induced hearing loss rats

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138147

So Young Kim , Jong Chan Jeon , Bohyeon Park , Do Eun Kim

Background

The extracellular baskets of cochlear inner hair cell (IhC) ribbon synapses have been suggested to regulate synaptic coupling. This study aimed to investigate the expression of components of the extracellular baskets of the IhCs, chondroitin sulfate proteoglycans (CSPGs) and a hyaluronan and proteoglycan link protein 1 (HAPLN1) in the cochlea and auditory nerve. In addition, changes in CSPGs and HAPLN1 in noise-injured cochleae were examined.

Methods

The expression of CSPGs, including aggrecan (ACAN), brevican (BCAN), neurocan (NCAN), and HAPLN1, was evaluated in the cochleae of 2-month-old Sprague–Dawley (SD) rats. The expression of CSPGs and HAPLN1 in cochleae and auditory nerves was compared to that in 3-month-old noise-exposed SD rats during the developmental period. The cochlear immunohistochemistry (IHC) and cochlear whole mount immunofluorescence studies were conducted for ACAN, BCAN, NCAN, and HAPLN1. To examine the large ganglial cells in auditory nerves, IHC was conducted for parvalbumin (PV), glutamate decarboxylase 67 (GAD67), postsynaptic density protein 95 (PSD95), and glial fibrillary acidic protein (GFAP). In situ hybridization was performed for BCAN.

Results

ACAN, BCAN, and HAPLN1 expression was detected in the IhCs and was decreased tendency in noise-injured cochleae. In the spiral ganglial cell (SGC) region, ACAN and NCAN were expressed without the expression of BCAN. In auditory nerves, large ganglionic cells (LGCs) are encased with perineuronal nets (PNNs), which express PV, GAD67, and PSD95. The mRNA expression of BCAN was noted in SGCs and glial cells of auditory nerves.

Conclusions

The extracellular baskets of IhCs revealed the expression of CSPGs and HAPLN1, which was attenuated in noise-exposed cochleae. In auditory nerves, PV-positive LGCs with inhibitory synapses presented PNNs. The protein expression of BCAN was restricted to the extracellular baskets of IhC but not to the SGC region. However, the mRNA expression of BCAN in SGCs was not affected.

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引用次数: 0

Alterations in iron levels in the locus coeruleus of a transgenic Alzheimer’s disease rat model

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138151

Kayla Aishwarya Bhagaloo , Lei Yu , Elizabeth A. West , Daniel J. Chandler , Natalia Shcherbik

Iron is essential for brain function, acting as a cofactor for enzymes involved in neurotransmitter synthesis and metabolism. However, dysregulated iron homeostasis is increasingly linked to neurodegenerative diseases, including Alzheimer’s disease (AD). The locus coeruleus (LC), a norepinephrine-producing brainstem nucleus, is among the earliest regions affected in AD, yet its iron dynamics remain poorly understood. This study presents the first comprehensive analysis of iron content in the LC by combining a transgenic AD rat model, precise anatomical isolation, and Inductively Coupled Plasma Mass Spectrometry for high-sensitivity metal quantification. This approach enabled the profiling of iron and zinc concentrations in the LC, uncovering novel insights into iron dysregulation in AD. We observed a significant genotype-specific increase in LC iron levels in TgF344-AD rats compared to wild-type controls. Notably, our findings reveal distinct iron alterations in TgF344-AD rats, suggesting a previously unrecognized role for iron homeostasis in LC dysfunction. These results provide new perspectives on iron dysregulation in AD pathology and its potential as a therapeutic target.

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引用次数: 0

Nasal mucosal mesenchymal stem cells promote repair of sciatic nerve injury in rats by modulating the inflammatory microenvironment 鼻黏膜间充质干细胞通过调节炎症微环境促进大鼠坐骨神经损伤的修复

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2024.138112

Yushi Tang , Yilu Li , Wenhui Yang , Zhenxing Tao , Wentao Shi , Mengyuan Yu , Bai Xu , Xiaojie Lu

Sciatic nerve injury (SNI) represents the most prevalent form of peripheral nerve damage, resulting in the rapid activation of macrophages into the M1 phenotype following injury. This activation induces an inflammatory microenvironment that negatively impacts nerve regeneration. Ectodermal mesenchymal stem cells (EMSCs), isolated from nasal mucosa, possess the capacity for multidirectional differentiation and exhibit immunomodulatory effects. Modulating macrophage polarization to create a favorable environment for nerve repair may represent a potential approach to facilitate nerve recovery. This investigation sought to explore the effects of EMSCs transplantation on macrophage polarization and nerve regeneration in SNI, as well as to identify the underlying mechanisms. An in vivo SNI model was established, and behavioral and histological analyses demonstrated that EMSCs transplantation facilitated nerve function recovery. Furthermore, immunofluorescence and Western blot assays revealed an increase in M2 macrophage presence and the secretion of anti-inflammatory cytokines following EMSCs transplantation, thereby promoting nerve regeneration. In vitro, EMSCs were found to enhance M2 macrophage polarization and the production of anti-inflammatory factors. Additionally, it was confirmed that EMSCs regulate macrophage polarization through the PI3K/AKT/NF-κB signaling pathway, thereby fostering an optimal inflammatory environment for nerve regeneration.

坐骨神经损伤（SNI）是最常见的周围神经损伤形式，导致巨噬细胞在损伤后迅速激活为M1表型。这种激活诱导炎症微环境，对神经再生产生负面影响。外胚层间充质干细胞（Ectodermal mesenchymal stem cells, EMSCs）是一种从鼻黏膜中分离出来的具有多向分化能力和免疫调节作用的细胞。调节巨噬细胞极化为神经修复创造有利的环境可能是促进神经恢复的一种潜在途径。本研究旨在探讨EMSCs移植对SNI巨噬细胞极化和神经再生的影响，并确定其潜在机制。建立体内SNI模型，行为学和组织学分析表明，EMSCs移植促进了神经功能的恢复。此外，免疫荧光和Western blot检测显示，EMSCs移植后M2巨噬细胞的存在和抗炎细胞因子的分泌增加，从而促进神经再生。体外实验发现，EMSCs可增强M2巨噬细胞极化和抗炎因子的产生。此外，EMSCs通过PI3K/AKT/NF-κB信号通路调节巨噬细胞极化，从而为神经再生提供最佳炎症环境。

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引用次数: 0

Augmentation of neural stem cell proliferation and enhanced differentiation toward neural and oligodendroglia lineages through sonic hedgehog pathway: Cross-activation of Notch1 and SOX10 通过sonic hedgehog通路增强神经干细胞增殖并向神经和少突胶质细胞谱系分化：Notch1和SOX10的交叉激活

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2024.138098

Arsalan Azizi , Nahid Azarmehr , Maryam Hashemi Shahraki , Roya Aryanpour , Elham Enanat , Parisa Danaee fard , Mehrzad Jafari Barmak , Amir Ghanbari

The study aimed to understand the impact of the sonic-hedge signal pathway (SHH) on mouse neural stem cells. We manipulated the pathway using purmorphamine (Pur) and Gant 61 and observed the effects on cell viability, neurosphere formation, and gene expression. We found that activating the SHH pathway with Pur increased cell viability, neurosphere formation, and the expression of specific genes, promoting the differentiation of neural stem cells into mature cells. Conversely, inhibiting the SHH pathway with Gant61 decreased cell viability and neurosphere formation and suppressed differentiation. This suggests that the SHH pathway plays a crucial role in determining the fate of neural stem cells.

这项研究旨在了解声音对冲信号通路（SHH）对小鼠神经干细胞的影响。我们使用purmorphamine （Pur）和gant61操纵该通路，观察其对细胞活力、神经球形成和基因表达的影响。我们发现，用Pur激活SHH通路可以提高细胞活力、神经球形成和特定基因的表达，促进神经干细胞向成熟细胞的分化。相反，用Gant61抑制SHH通路会降低细胞活力和神经球形成，并抑制分化。这表明SHH通路在决定神经干细胞的命运中起着至关重要的作用。

引用次数: 0

Prolactin levels increased by physical exercise correlate with platelet monoamine oxidase activity: Evidence linking platelet MAO with serotonin release capacity 体育锻炼增加催乳素水平与血小板单胺氧化酶活性相关：血小板MAO与血清素释放能力相关的证据

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138116

Jaanus Harro , Diva Eensoo , Silva Suvi , Saima Timpmann , Vahur Ööpik

Objective

Lower platelet monoamine oxidase (MAO) activity has consistently been associated with excessive risk-taking and general psychiatric vulnerability. How this peripheral measure can represent presumably centrally regulated complex behaviours is not clear but platelet MAO activity has been suggested to reflect the capacity of serotonin release in the brain. Secretion of prolactin is in part under serotonergic control and indicates serotonin release capacity.

Methods

We have assessed release of prolactin and other exercise-induced hormones in response to strenuous physical exercise in twenty male subjects and examined its association with platelet MAO activity as measured radioenzymatically.

Results

Increase in prolactin levels was positively correlated with platelet MAO activity. Levels of cortisol, growth hormone and aldosterone were also raised by exercise, but these increases were not associated with platelet MAO activity. Unexpectedly, aldosterone levels before exercise were also in a positive correlation with platelet MAO activity.

Conclusion

The finding that exercise-induced prolactin release is associated with MAO activity in platelets indirectly supports the notion that platelet MAO activity is a marker of central serotonin release capacity.

目的：较低的血小板单胺氧化酶（MAO）活性一直与过度冒险和一般精神脆弱性有关。这种外周测量如何能够代表可能是中央调控的复杂行为尚不清楚，但血小板MAO活性已被认为反映了大脑中血清素释放的能力。催乳素的分泌部分受血清素能控制，表明血清素的释放能力。方法：我们评估了20名男性受试者在剧烈体育锻炼后泌乳素和其他运动诱导激素的释放，并通过放射酶测定其与血小板MAO活性的关系。结果：催乳素水平升高与血小板MAO活性呈正相关。皮质醇、生长激素和醛固酮的水平也因运动而升高，但这些升高与血小板MAO活性无关。出乎意料的是，运动前的醛固酮水平也与血小板MAO活性呈正相关。结论：运动诱导的催乳素释放与血小板MAO活性相关的发现间接支持了血小板MAO活性是中枢血清素释放能力的标志的观点。

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引用次数: 0

Differential effects of statins on the anti-dyskinetic activity of sub-anesthetic ketamine 他汀类药物对亚麻醉氯胺酮抗运动障碍活性的不同影响。

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138114

Mitchell J. Bartlett , Carolyn J. Stopera , Stephen L. Cowen , Scott J. Sherman , Torsten Falk

Sub-anesthetic ketamine has been demonstrated to reduce abnormal involuntary movements (AIMs) in preclinical models of L-DOPA-induced dyskinesia (LID) and retrospective Parkinson’s disease (PD) case reports. In this study, we examined the effects on LID of two different statins alone and in combination with ketamine in unilateral 6-hydroxydopamine-lesioned male rats, the standard model for preclinical LID studies. Ketamine attenuated the development of AIMs, while the non-polar lovastatin only showed anti-dyskinetic activity early in the priming period but did not prevent the development of LID, and the polar pravastatin showed no anti-dyskinetic activity. Furthermore, our main result is that pravastatin blocked the long-term neuroplastic anti-dyskinetic effects of ketamine, while lovastatin did not. This study shows two different statins affect LID and the anti-dyskinetic activity of ketamine differentially, pointing to an important drug interaction. The results further inform and support ongoing clinical testing of sub-anesthetic ketamine to treat LID in individuals with PD.

在左旋多巴诱导的运动障碍（LID）的临床前模型和回顾性帕金森病（PD）病例报告中，亚麻醉氯胺酮已被证明可以减少异常不自主运动（AIMs）。在这项研究中，我们研究了两种不同的他汀类药物单独使用和与氯胺酮联合使用对单侧6-羟多巴胺损伤的雄性大鼠（临床前LID研究的标准模型）的LID的影响。氯胺酮可减弱AIMs的发展，而非极性洛伐他汀仅在启动期早期表现出抗运动障碍活性，但不能阻止LID的发展，极性普伐他汀无抗运动障碍活性。此外，我们的主要结果是普伐他汀阻断了氯胺酮的长期神经可塑性抗运动障碍作用，而洛伐他汀没有。本研究显示两种不同的他汀类药物对LID和氯胺酮抗运动障碍活性的影响不同，指出了一种重要的药物相互作用。该结果进一步为亚麻醉氯胺酮治疗PD患者LID的临床试验提供了信息和支持。

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引用次数: 0

Cognitive response to energy variations in Non-Contact tactile sensations interface using Laser-Induced plasma 激光诱导等离子体对非接触式触觉界面能量变化的认知反应。

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138119

Kyu-Beom Kim , Min-Kyun Lee , Yong-Bin Jeong , Jeong-Min Kim , Mi-Hyun Choi , Hyung-Sik Kim , Byung-Chan Min , Soon-Cheol Chung

Laser-induced plasma technology provides a novel method for generating tactile sensations without physical contact, offering precise and controlled stimulation. However, the impact of varying energy levels on human cognitive and perceptual responses is not yet fully understood. This study aimed to present tactile sensations using laser-induced plasma in a non-contact manner and investigate the cognitive characteristics linked to changes in the plasma’s energy parameters, specifically Pulse Width (PW) and Set Current (SC). The experiment was conducted with 35 right-handed male and female adults in their 20 s. Tactile stimuli were presented under two conditions: Condition 1 fixed SC and varied PW, while Condition 2 fixed PW and varied SC, with each condition adjusted to produce three energy levels. Subjective evaluations included assessments of tactile intensity and vocabulary using a 5-point scale. Sixteen terms related to tactile sensations were evaluated. A two-way repeated measures analysis of variance was used to compare scores across both factors (Condition and Energy). The results showed that as the energy level increased, the perceived intensity also rose. In the vocabulary evaluation, sensations such as “Tapping” and “Rapping” were predominant, with higher scores at increased energy levels. No significant differences were observed between the two conditions for either tactile intensity or vocabulary evaluations. In conclusion, varying the energy magnitude of laser-induced plasma can produce tactile sensations of different intensities, and the parameters used in this study successfully evoked specific sensations like slow vibration.

激光诱导等离子体技术提供了一种新的方法，可以在没有物理接触的情况下产生触觉，提供精确和可控的刺激。然而，不同能量水平对人类认知和知觉反应的影响尚未完全了解。本研究旨在以非接触方式呈现激光诱导等离子体的触觉，并研究与等离子体能量参数变化有关的认知特征，特别是脉冲宽度（PW）和设定电流（SC）。实验对象是35名20多岁的右撇子男女。触觉刺激在两种条件下呈现：条件1固定的SC和变化的PW，条件2固定的PW和变化的SC，每个条件调整产生三个能量水平。主观评估包括使用5分制的触觉强度和词汇量评估。评估了16个与触觉相关的术语。使用双向重复测量方差分析来比较两个因素（条件和能量）的得分。结果表明，随着能量等级的升高，感知强度也随之升高。在词汇量评估中，“敲击”和“说唱”等感觉占主导地位，能量水平越高，得分越高。在两种情况下，触觉强度和词汇评价均无显著差异。综上所述，改变激光诱导等离子体的能量大小可以产生不同强度的触觉，本研究中使用的参数成功地唤起了慢振动等特定的感觉。

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引用次数: 0

Corrigendum to "Hippocampal iron overload and spatial reference memory impairment: Insights from a rat model" [843 (2024) 138014].

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138133

Yihao Sun, Bin Tian, Jiali Liang, Meiru Bu, Xi Deng, Kemei Deng, Muliang Jiang, Bihong Chen

引用次数: 0

Ivabradine reduces neuropathic pain after spinal cord injury by inhibiting excitatory synaptic transmission in the spinal dorsal horn 伊伐布雷定通过抑制脊髓背角的兴奋性突触传递减轻脊髓损伤后的神经性疼痛。

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-02-06 DOI: 10.1016/j.neulet.2025.138113

Nobuko Ohashi , Masayuki Ohashi , Rintaro Hoshino , Hiroyuki Deguchi , Hiroshi Baba

Spinal cord injuries (SCIs) can lead to severe neuropathic pain and increased risk of myocardial infarction and heart failure; therefore, the use of analgesics against SCI-induced pain should be minimized because of their adverse effects on the cardiovascular system. Ivabradine, a blocker of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, is used as a bradycardic agent, but recent studies focused on it as an analgesic agent for peripheral neuropathic pain. However, the analgesic effects of ivabradine on central neuropathic pain, such as SCI-induced pain, have not been examined. The aim of this study was to investigate the spinal analgesic effects of ivabradine on central neuropathic pain induced by SCI. Ivabradine induced analgesia in both spontaneous pain-related behavior and mechanical allodynia in SCI-induced pain (6–7 rats/group; p < 0.01). In immunohistochemical staining analyses, ivabradine suppressed phosphorylation of extracellular signal-regulated kinases activated by SCI-induced pain in the superficial spinal dorsal horn (6 rats/group; p < 0.01). In in vitro whole-cell patch-clamp analysis, ivabradine decreased the frequency of miniature excitatory postsynaptic currents in substantia gelatinosa neurons (11–12 rats/group; p < 0.01). We concluded that ivabradine reduces SCI-induced pain by inhibiting excitatory synaptic transmission in the spinal dorsal horn.

脊髓损伤（SCIs）可导致严重的神经性疼痛，增加心肌梗死和心力衰竭的风险；因此，由于镇痛药对心血管系统的不良影响，应尽量减少对sci引起的疼痛的使用。伊伐布雷定是一种超极化激活的环核苷酸门控阳离子（HCN）通道阻滞剂，被用作心动过缓的药物，但最近的研究主要集中在它作为周围神经性疼痛的镇痛药物。然而，伊伐布雷定对中枢神经性疼痛（如sci引起的疼痛）的镇痛作用尚未得到研究。本研究旨在探讨伊伐布雷定对脊髓损伤所致中枢神经性疼痛的镇痛作用。伊伐布雷定诱导自发性疼痛相关行为和机械性疼痛的镇痛(6-7只大鼠/组；p

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引用次数: 0