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Mapping the aging brain: Insights into microstructural changes from free water-corrected fractional anisotropy
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-23 DOI: 10.1016/j.neulet.2025.138120
Abigail E. Bower , Jae Woo Chung , Roxana G. Burciu
Aging has a significant impact on brain structure, demonstrated by numerous MRI studies using diffusion tensor imaging (DTI). While these studies reveal changes in fractional anisotropy (FA) across different brain regions, they tend to focus on white matter tracts and cognitive regions, often overlooking gray matter and motor areas. Additionally, traditional DTI metrics can be affected by partial volume effects. To address these limitations and gain a better understanding of microstructural changes across the whole brain, we utilized free water-corrected fractional anisotropy (FAt) to examine aging-related microstructural changes in a group of 20 young adults (YA) and 24 older adults (OA). A voxel-wise analysis revealed that YA had higher FAt values predominantly in white matter tracts associated with both motor and non-motor functions. In contrast, OA showed higher levels of FAt primarily in gray matter regions, including both subcortical and cortical motor areas, and occipital and temporal cortices. Complementing these cross-sectional results, correlation analyses within the OA group showed that many of these changes are further exacerbated with increasing age, underscoring the progressive nature of these microstructural alterations. In summary, the distinct patterns of FAt changes in gray versus white matter with aging suggest different underlying mechanisms. While white matter FAt values decrease, likely due to axonal degeneration, the increase in gray matter FAt could reflect either compensatory processes or pathological changes. Including behavioral data in future studies will be crucial for understanding the functional implications of these microstructural gray matter changes and their effects on cognitive and motor functions.
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引用次数: 0
Repeated exposure to antibiotics exhibits anxiety-like behaviors with a reduction in neurogenesis in the ventral hippocampus of dentate gyrus
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-20 DOI: 10.1016/j.neulet.2025.138131
Kohei Takahashi , Kazuhiro Kurokawa , Kazuya Miyagawa , Atsumi Mochida-Saito , Hiroshi Takeda , Minoru Tsuji
Disruption of gut microbiota balance is known to contribute to the development of anxiety; however, it remains unclear whether dysbiosis-induced anxiety involves the glycogen synthase kinase-3β (GSK-3β)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway and neurogenesis in the ventral hippocampal dentate gyrus (DG). In this study, Male ddY mice were administered an antibacterial cocktail to induce dysbiosis. The dysbiosis model displayed anxiety-like behaviors in the hole-board and elevated plus-maze tests, decreased the phosphorylation levels of GSK-3β (Ser9) and CREB, decreased the expression level of BDNF in the ventral hippocampus, and reduced neurogenesis in the ventral hippocampal DG. This suggests that dysbiosis-induced anxiety-like behaviors are associated with reduced neurogenesis in the ventral hippocampal DG via the GSK-3β/CREB/BDNF pathway.
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引用次数: 0
Latent bladder hypersensitivity induced by neonatal cystitis in rats unmasked by segmental but not hetero-segmental inflammation 新生儿膀胱炎引起的潜伏性膀胱超敏反应未被节段性而非异节段性炎症掩盖。
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2024.138090
Timothy J. Ness, Cary DeWitte
Rats which experienced neonatal bladder inflammation (NBI) have been demonstrated to exhibit latent bladder hypersensitivity with a nociceptive component that becomes unmasked by a second inflammatory insult as an adult. Manifested as augmented reflex and neuronal responses to urinary bladder distension (UBD), these NBI-induced changes are revealed by using inflammation of nearby structures as an adult pretreatment. The effect of inflammation in distant structures is not known. These studies examined visceromotor reflex responses and lumbosacral spinal dorsal horn neuronal responses to UBD in rats and compared effects of segmental (hindpaw) versus hetero-segmental (forepaw or face) inflammatory pretreatments in 192 female Sprague-Dawley rats raised from birth. On postnatal days 14–16 these rats underwent either NBI or control procedures. As adults, these rats received control injections or 0.1 ml Complete Freund’s Adjuvant (CFA) injections into one of four sites. Three days later they were studied in reflex or spinal single-cell neuronal experiments where responses were evoked by UBD. Visceromotor responses to UBD were more robust in rats which had injections in the hindpaw (either side) but were not significantly affected by forepaw or facial injections. Similar results were identified in L6/S1 neurons with more robust UBD-evoked responses observed in rats receiving hindpaw CFA injections but not forepaw injections. These results indicate that latent bladder hypersensitivity induced by NBI is made manifest by segmental, but not hetero-segmental inflammatory stimuli. This observation correlates with pain in patients with interstitial cystitis who often have flares in symptoms associated with inflammation of nearby structures.
经历过新生儿膀胱炎症(NBI)的大鼠已被证明表现出潜在的膀胱超敏反应,其中含有一种伤害性成分,这种成分在成年后的第二次炎症侮辱中被揭示出来。表现为增强反射和神经元对膀胱膨胀(UBD)的反应,这些nbi诱导的变化通过使用附近结构的炎症作为成人预处理来揭示。炎症对远端组织的影响尚不清楚。这些研究检查了大鼠对UBD的内脏运动反射反应和腰骶脊髓背角神经元反应,并比较了192只雌性Sprague-Dawley大鼠的节段性(后爪)和异节段性(前爪或面部)炎症预处理的效果。在出生后14-16天,这些大鼠接受NBI或对照程序。成年后,这些大鼠接受对照注射或在四个部位之一注射0.1 ml完全弗氏佐剂(CFA)。三天后,他们在反射或脊髓单细胞神经元实验中进行了研究,其中UBD引起了反应。后爪(两侧)注射的大鼠对UBD的脏器运动反应更为强烈,而前爪或面部注射的大鼠对UBD的反应没有显著影响。在L6/S1神经元中也发现了类似的结果,在后爪注射CFA的大鼠中观察到更强的ubd诱发反应,而在前爪注射的大鼠中则没有。这些结果表明,NBI引起的潜伏性膀胱超敏反应是由节段性炎症刺激引起的,而不是异节段性炎症刺激。这一观察结果与间质性膀胱炎患者的疼痛有关,这些患者通常有与附近结构炎症相关的症状发作。
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引用次数: 0
Oligodendrocyte differentiation on murine decellularized brain tissue 小鼠脱细胞脑组织少突胶质细胞分化。
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2024.138079
Hinata Nishimura , Aurelien Kerever , Kana Kato , Tatsuki Ono , Shiomi Nakayama , Takahiro Tanaka , Ryusei Abe , Eri Arikawa-Hirasawa
Loss of oligodendrocytes causes severe neurological damage. Oligodendrogenesis is the production of new oligodendrocytes throughout life and includes several developmental stages starting from oligodendrocyte precursor cells (OPCs).
The GPR17-expressing cell population, an important intermediate stage in oligodendrocyte development, acts as a reservoir responding to brain injury and ischemia. GPR17 plays a complex role in oligodendrocyte maturation and response to injury; its activation promotes differentiation into more mature phenotypes. However, our understanding of GPR17-expressing oligodendrocytes in vitro remains limited.
No methods have been elucidated for studying these short-lived and changeable cell populations using culture systems.
The extracellular matrix (ECM) plays an important role in regulating the proliferation and differentiation of these cells; however, conventional two-dimensional culture systems cannot reproduce the complex structure and environmental conditions of the ECM in vivo.
Herein, a culture system with decellularized brain tissue that retains organized ECM scaffolds was introduced to better mimic the in vivo environment. This system enabled the study of interactions between OPCs, ECM, and other cell types. Neurospheres containing progenitor cells that differentiate into oligodendrocyte lineage cells, neurons, and astrocytes were transplanted into decellularized brain slices. The results showed that this method not only promoted stem cell differentiation but also significantly enhanced differentiation into oligodendrocytes when supplemented with oligo buffer.
This model system provides a better understanding of the interaction between OPCs and the ECM and a novel approach for studying the differentiation of GPR17-expressing cells, which may be useful for future therapeutic strategies for promoting remyelination and central nervous system repair.
少突胶质细胞的缺失会导致严重的神经损伤。少突胶质细胞发生是指在整个生命过程中产生新的少突胶质细胞,包括从少突胶质前体细胞(OPCs)开始的几个发育阶段。表达gpr17的细胞群是少突胶质细胞发育的重要中间阶段,是脑损伤和缺血反应的储存库。GPR17在少突胶质细胞成熟和损伤反应中发挥复杂作用;它的激活促进分化为更成熟的表型。然而,我们对体外表达gpr17的少突胶质细胞的了解仍然有限,没有办法阐明利用培养系统研究这些寿命短且易变的细胞群。细胞外基质(extracellular matrix, ECM)在调节这些细胞的增殖和分化中起重要作用;然而,传统的二维培养系统无法在体内再现ECM的复杂结构和环境条件。本文引入了一种具有脱细胞脑组织的培养系统,该培养系统保留有组织的ECM支架,以更好地模拟体内环境。该系统能够研究OPCs、ECM和其他细胞类型之间的相互作用。将含有分化为少突胶质细胞系细胞、神经元和星形胶质细胞的祖细胞的神经球移植到去细胞化的脑切片中。结果表明,该方法不仅能促进干细胞的分化,而且在添加寡球缓冲液的情况下,能显著增强向少突胶质细胞的分化。该模型系统为OPCs与ECM之间的相互作用提供了更好的理解,并为研究表达gpr17的细胞的分化提供了一种新的方法,这可能有助于未来促进髓鞘再生和中枢神经系统修复的治疗策略。
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引用次数: 0
Oral administration of crocin reverses memory loss induced by ethanol and nicotine abstinence in adolescent male rats 口服藏红花素可逆转乙醇和尼古丁戒断引起的青春期雄性大鼠记忆丧失。
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2024.138077
Samaneh Kakhki , Ali Abbaszade-Cheragheali , Seyyed Pouria Tafti , Atefeh Shirinzadeh Feizabadi , S. Mohammad Ahmadi-Soleimani , Farimah Beheshti

Purpose

Regarding a wide variety of researches conducted with various therapeutic effect of crocin, the main constituent of saffron, the current study aims to assess the efficacy of crocin to improve learning and memory impairment caused by withdrawal following concurrent usage of ethanol (Eth) and nicotine (Nic) in adolescent male rats.

Methods

In order to test memory fucntion, Morris water maze and passive avoidance methods were applied in male Wistar rats undergone adolescent Nic-Eth withdrawal and the effect of crocin treatment was assessed at both behavioral and biochemical levels. The biochemical parameters included the inflammatory cytokines, indicators of oxidative stress and cholinergic metabolism within the hippocampla tissues. Animals were divided into 7 experimental groups as follows: 1) control (saline + saline), 2) nicotine + ethanol, 3–5) nicotine + ethanol + crocin (three doses), 6) nicotine + ethanol + bupropion + naloxone and 7) saline + crocin.

Results

Results indicated that crocin treatment effectively prevented the Nic-Eth withdrawal induced behavioral manifestations of memory impairment when assessed by Morris water maze and passive avoidance tests. In addition, the biochemical alterations (in inflammatory, oxidative and cholinergic parameters) induced by Nic-Eth withdrawal were also ameliorated in rats treated by crocin. Interestingly, the mentioned ameliorative effect of crocin was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration, when administered at high doses.

Conclusion

We would like to suggest the crocin treatment as an alternative medication for the management of Nic − Eth withdrawal, however, further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.
目的:对藏红花的主要成分藏红花素的各种治疗作用进行了广泛的研究,本研究旨在评估藏红花素对青少年雄性大鼠同时使用乙醇(Eth)和尼古丁(Nic)后戒断引起的学习和记忆障碍的改善效果。方法:采用Morris水迷宫法和被动回避法对青春期戒断Nic-Eth的雄性Wistar大鼠进行记忆功能测试,并从行为和生化两方面评价藏红花素治疗的效果。生化指标包括海马组织内炎症因子、氧化应激指标和胆碱能代谢指标。动物被分成7个实验小组如下:1)控制(盐水 + 盐水),2)尼古丁 + 乙醇,乙醇3 - 5)尼古丁 +  + 藏红花素(三剂),6)尼古丁 + 乙醇 + 安非他酮 + 纳洛酮和7)盐水 + 藏红花素。结果:Morris水迷宫和被动回避实验结果显示,藏红花素可有效预防Nic-Eth戒断所致的记忆障碍行为表现。此外,藏红花素还能改善大鼠Nic-Eth戒断引起的生化改变(炎症、氧化和胆碱能参数)。有趣的是,在大多数实验中,发现藏红花素的上述改善作用是剂量依赖的,并且在高剂量时,与安非他酮和纳洛酮共给药几乎相同。结论:我们建议将藏红花素治疗作为治疗Nic - Eth戒断的一种替代药物,但需要进一步的研究来评估未知的副作用和药物在人类受试者中的高剂量耐受性。
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引用次数: 0
Cortical beta oscillation in brain slices of hemi parkinsonian mice 半帕金森小鼠脑切片皮层β振荡。
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2025.138128
Aidán Ortega , Antonio Laville , Montserrat Padilla-Orozco , Yohana Parrado , Dagoberto Tapia , Miguel Serrano-Reyes , Janintzitzic López-Niño , Héctor A. Vázquez-Vázquez , Elvira Galarraga , José Bargas
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to significant motor and non-motor symptoms. Beta oscillations in cortical areas are a pathognomonic sign. Here we ask whether these oscillations can be recorded in in vitro cortical tissue despite severing the cortico-basal ganglia-thalamo-cortical loop. M1/M2 cortex of hemi parkinsonian mice (6-OHDA) was recorded with multielectrode arrays (MEAs). Spectral decomposition analysis shows a significantly augmented beta band power with respect to controls. The administration of L-DOPA diminished this exacerbated beta rhythm. This result suggests that plastic changes induced by dopamine (DA) depletion remain in isolated cortical tissue even when the complete circuit is no longer present. This finding brings the opportunity to test anti-parkinsonian drugs in vitro by quantifying cortical beta band power.
帕金森病(PD)是一种神经退行性疾病,其特征是黑质致密部多巴胺能神经元的进行性丧失,导致明显的运动和非运动症状。皮层区域的β振荡是一种病征。在这里,我们询问这些振荡是否可以在体外皮层组织中记录,尽管切断了皮质-基底神经节-丘脑-皮层回路。采用多电极阵列(MEAs)对半帕金森小鼠M1/M2皮质(6-OHDA)进行记录。光谱分解分析表明,相对于控制,显著增加β波段功率。左旋多巴的使用减少了这种加剧的β节律。这一结果表明,多巴胺(DA)耗竭引起的可塑性变化在孤立的皮质组织中仍然存在,即使完整的回路不再存在。这一发现为通过量化皮质β带功率来测试抗帕金森病药物的体外测试提供了机会。
{"title":"Cortical beta oscillation in brain slices of hemi parkinsonian mice","authors":"Aidán Ortega ,&nbsp;Antonio Laville ,&nbsp;Montserrat Padilla-Orozco ,&nbsp;Yohana Parrado ,&nbsp;Dagoberto Tapia ,&nbsp;Miguel Serrano-Reyes ,&nbsp;Janintzitzic López-Niño ,&nbsp;Héctor A. Vázquez-Vázquez ,&nbsp;Elvira Galarraga ,&nbsp;José Bargas","doi":"10.1016/j.neulet.2025.138128","DOIUrl":"10.1016/j.neulet.2025.138128","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to significant motor and non-motor symptoms. Beta oscillations in cortical areas are a pathognomonic sign. Here we ask whether these oscillations can be recorded in <em>in vitro</em> cortical tissue despite severing the cortico-basal ganglia-thalamo-cortical loop. M1/M2 cortex of hemi parkinsonian mice (6-OHDA) was recorded with multielectrode arrays (MEAs). Spectral decomposition analysis shows a significantly augmented beta band power with respect to controls. The administration of L-DOPA diminished this exacerbated beta rhythm. This result suggests that plastic changes induced by dopamine (DA) depletion remain in isolated cortical tissue even when the complete circuit is no longer present. This finding brings the opportunity to test anti-parkinsonian drugs <em>in vitro</em> by quantifying cortical beta band power.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138128"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008925","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
Corrigendum to “Regional specific effect of saturated vs unsaturated fat on leptin receptor signalling in mice brain areas regulating feeding” [Neurosci. Lett. 793 (2023) 136996, 1–5 doi.org/10.1016/j.neulet.2022.136996] 更正:"饱和脂肪与不饱和脂肪对小鼠大脑中调节进食的瘦素受体信号的区域特异性影响" [Neurosci. Lett. 793 (2023) 136996, 1-5 doi.org/10.1016/j.neulet.2022.136996]。
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2024.138076
Jesús Fernandez-Felipe , Lucía L. López , Victoria Cano , Enrique Sánchez-Hita , A. Belén Sanz , Julie A. Chowen , Nuria Del Olmo , Mariano Ruiz-Gayo , Beatriz Merino
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引用次数: 0
The neural ensembles activated by propofol and isoflurane anesthesia across the whole mouse brain 异丙酚和异氟醚麻醉激活整个小鼠大脑的神经系统。
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2024.138080
Qian Zhang , Jin Ke , Guangfu Cui , Shen Qian , Weixin Qian , Sun-Wook Moon , Yanyan Sun , Tianwen Huang , Zaisheng Qin
General anesthesia has been widely used in surgical procedures. Propofol and isoflurane are the most commonly used injectable and inhaled anesthetics, respectively. The various adverse effects induced by propofol and isoflurane are highly associated with the anesthetic-dependent change of brain activities. In this work, we aim to delineate a brain-wide neuronal activity landscape of injectable versus inhaled anesthetics to understand the neural basis underlying the different physiological effects induced by these two major types of anesthetics. Through detailed scanning of the whole mouse brain subjected to propofol or isoflurane anesthesia, in total, we identified 17 subcortical regions, 3 of which (anterodorsal preoptic nucleus, ADP; lateral habenular, LHb; inferior olivary nucleus, ION) were specifically activated by propofol, and 3 (ventral part of the lateral septum, LSV; the intermediate part of the lateral septum, LSI; the solitary tract nucleus, Sol) were specifically activated by isoflurane, with the remaining 11 were activated by both two anesthetics. Moreover, within the 17 brain regions, ADP, SubCV (subcoeruleus nucleus, ventral part), PCRtA (parvicellular reticular nucleus, alpba part) and ION were newly identified that activated by propofol or isoflurane, respectively. By using Targeted Recombination in Active Populations (TRAP) technique, we further showed that propofol and isoflurane largely activate the same group of neurons in supraoptic nucleus (SON), but activate different groups of neurons in central amygdala (CeA). Our results reveals the neural ensembles activated by injectable and inhaled anesthetics, and provides detailed anatomical references for future studies on general anesthesia.
全身麻醉已广泛应用于外科手术。异丙酚和异氟醚分别是最常用的注射麻醉剂和吸入麻醉剂。异丙酚和异氟醚引起的各种不良反应与麻醉依赖性脑活动变化高度相关。在这项工作中,我们的目标是描绘注射麻醉药和吸入麻醉药的全脑神经元活动图景,以了解这两种主要麻醉药引起的不同生理效应的神经基础。通过对异丙酚或异氟醚麻醉下的小鼠全脑进行详细扫描,我们共鉴定出17个皮质下区域,其中3个区域(前嗅侧视前核,ADP;侧habenular, LHb;下橄榄核(ION)被异丙酚特异性激活,3(外侧隔腹侧部分,LSV;外侧隔的中间部分,LSI;孤立束核(Sol)被异氟醚特异性激活,其余11个被两种麻醉剂激活。此外,在17个脑区中,ADP、SubCV(蓝下核,腹侧部分)、PCRtA(细胞网状核,α部分)和ION分别被异丙酚或异氟醚激活。利用TRAP (Targeted Recombination in Active Populations)技术,我们进一步发现异丙酚和异氟醚在很大程度上激活了视上核(SON)的同一组神经元,但激活了中央杏仁核(CeA)的不同组神经元。我们的研究结果揭示了注射和吸入麻醉药激活的神经系统,为未来全身麻醉的研究提供了详细的解剖学参考。
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引用次数: 0
Effect of galanin-like peptide on hypothalamic kisspeptin expression in female Zucker fatty rats 甘丙肽样肽对雌性Zucker脂肪大鼠下丘脑kisspeptin表达的影响。
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2024.138081
Akiko Sakata , Kinuyo Iwata , Kimihiko Nakao , Yuyu Kunimura , Shunji Suzuki , Hitoshi Ozawa , Hirotaka Ishii
Kisspeptin and galanin-like peptide (GALP) neurons in the hypothalamic arcuate nucleus (ARC) are involved in gonadotropin-releasing hormone (GnRH) neuron-mediated pulsatile luteinizing hormone (LH) secretion. Zucker fatty (ZF) rats display a leptin receptor gene abnormality and suppressed pulsatile LH secretion. ZF rats reportedly exhibit low hypothalamic GALP and kisspeptin expression, and GALP administration induces LH release in ZF rats. Therefore, we performed a histochemical analysis to determine whether GALP-induced LH release is mediated by kisspeptin neurons in ZF rats. All ZF rats were ovariectomized and subcutaneously implanted with an estradiol tube before the central injection of GALP or vehicle. GALP administration increased the plasma LH concentration. However, no significant difference was observed in the number of Kiss1 cells and the proportion of Fos-positive Kiss1 cells. The number of c-Fos-positive GnRH neurons significantly increased after GALP administration. Our results suggest that hypothalamic GALP neurons promote LH release by activating GnRH neurons without the activation of kisspeptin neurons in the ARC.
下丘脑弓状核(ARC)中的Kisspeptin和galanin样肽(GALP)神经元参与了促性腺激素释放激素(GnRH)神经元介导的脉动性黄体生成素(LH)分泌。扎克脂肪大鼠(Zucker fatty,ZF)显示瘦素受体基因异常,脉冲式促黄体生成素(LH)分泌受到抑制。据报道,ZF大鼠的下丘脑GALP和kisspeptin表达量较低,给ZF大鼠注射GALP可诱导其释放LH。因此,我们进行了组织化学分析,以确定 GALP 诱导的 LH 释放是否由 ZF 大鼠的吻肽素神经元介导。在中心注射 GALP 或载体之前,所有 ZF 大鼠均切除卵巢并皮下植入雌二醇管。注射 GALP 可增加血浆 LH 浓度。然而,在 Kiss1 细胞数量和 Fos 阳性 Kiss1 细胞比例方面未观察到明显差异。给药 GALP 后,c-Fos 阳性的 GnRH 神经元数量明显增加。我们的研究结果表明,下丘脑GALP神经元通过激活GnRH神经元促进LH释放,而不激活ARC中的kisspeptin神经元。
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引用次数: 0
The diagnostic value and molecular mechanisms of LncRNA ZFAS1 in neuropathic pain LncRNA ZFAS1在神经性疼痛中的诊断价值及分子机制
IF 2.5 4区 医学 Q3 NEUROSCIENCES Pub Date : 2025-01-18 DOI: 10.1016/j.neulet.2024.138097
Yunchao Chu , Jing Chen , Huaqing Cui , Qiuyi Xie , Shasha Mei

Objective

Long non-coding RNA (lncRNA) has been playing an increasingly significant role in neuropathic pain (NP). This study aimed to investigate the clinical significance and mechanism of LncRNA ZNFX1 antisense RNA 1 (ZFAS1) in NP.

Methods

92 patients with NP and 85 healthy controls were enrolled, and a rat NP model was constructed by chronic constrictive injury (CCI). LPS-induced microglia BV2 cells were used to construct an in vitro cellular model. RT-qPCR analysis of the mRNA levels of ZFAS1, miR-421, and Iba-1 (markers of microglia activation). Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to assess mechanosensitive and thermal nociceptive allergic responses. ELISA assay for pro-inflammatory factors and anti-inflammatory factors expression. ROC assay for the diagnostic value of ZFAS1. Validation of the targeting between ZFAS1 and miR-421 by dual luciferase reporter assay.

Results

ZFAS1 significantly increased while miR-421 significantly decreased in individuals with NP, in a rat model of CCI, and in LPS-induced microglial cells. Functionally, miR-421 directly targeted ZFAS1. ZFAS1 levels could significantly differentiate between NP patients and control (AUC = 0.910). Low expression of ZFAS1 significantly alleviated PWL and PWT in CCI rats. Elevated neuro-proinflammatory factors and decreased anti-inflammatory factors in CCI rats were significantly reversed by low expression of ZFAS1, but this is partially weakened by low expression of miR-421. Moreover, silencing ZFAS1 hindered the upregulation of Iba-1 expression induced by LPS, which was rescued significantly by miR-421.

Conclusion

Elevated ZFAS1 is a potential bio-diagnostic marker for NP. Inhibition of ZFAS1 may alleviate NP progression by inhibiting microglia activation and neuro-inflammatory responses.
目的:长链非编码RNA (lncRNA)在神经性疼痛(NP)中发挥着越来越重要的作用。本研究旨在探讨LncRNA ZNFX1反义RNA 1 (ZFAS1)在NP中的临床意义及作用机制。方法:选取92例NP患者和健康对照,建立慢性缩窄性损伤大鼠NP模型。采用脂多糖诱导的小胶质细胞BV2构建体外细胞模型。RT-qPCR分析ZFAS1、miR-421和Iba-1(小胶质细胞激活标志物)的mRNA水平。用足部戒断阈值(PWT)和足部戒断潜伏期(PWL)评估机械敏感性和热伤害性过敏反应。ELISA法检测促炎因子和抗炎因子的表达。ROC测定ZFAS1的诊断价值。通过双荧光素酶报告基因试验验证ZFAS1和miR-421之间的靶向性。结果:在NP个体、CCI大鼠模型和lps诱导的小胶质细胞中,ZFAS1显著升高,miR-421显著降低。在功能上,miR-421直接靶向ZFAS1。ZFAS1水平在NP患者和对照组之间具有显著差异(AUC = 0.910)。低表达ZFAS1可显著减轻CCI大鼠PWL和PWT。ZFAS1的低表达显著逆转了CCI大鼠神经促炎因子升高和抗炎因子降低,但miR-421的低表达部分削弱了这一点。此外,沉默ZFAS1阻碍了LPS诱导的Iba-1表达上调,miR-421可显著挽救Iba-1表达上调。结论:ZFAS1升高是NP潜在的生物诊断标志物。抑制ZFAS1可能通过抑制小胶质细胞激活和神经炎症反应来缓解NP进展。
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引用次数: 0
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Neuroscience Letters
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