首页 > 最新文献

ASN NEURO最新文献

英文 中文
All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration. 所有PNS都是一个阶段:移植骨髓细胞在周围神经再生中发挥免疫调节作用。
IF 3.9 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231167281
Gonzalo Piñero, Marianela Vence, Marcos L Aranda, Magalí C Cercato, Paula A Soto, Vanina Usach, Patricia C Setton-Avruj

Summary statement: Bone marrow cell transplant has proven to be an effective therapeutic approach to treat peripheral nervous system injuries as it not only promoted regeneration and remyelination of the injured nerve but also had a potent effect on neuropathic pain.

摘要:骨髓细胞移植已被证明是治疗外周神经系统损伤的有效治疗方法,因为它不仅促进了受损神经的再生和髓鞘再生,而且对神经性疼痛也有显著影响。
{"title":"All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration.","authors":"Gonzalo Piñero, Marianela Vence, Marcos L Aranda, Magalí C Cercato, Paula A Soto, Vanina Usach, Patricia C Setton-Avruj","doi":"10.1177/17590914231167281","DOIUrl":"10.1177/17590914231167281","url":null,"abstract":"<p><strong>Summary statement: </strong>Bone marrow cell transplant has proven to be an effective therapeutic approach to treat peripheral nervous system injuries as it not only promoted regeneration and remyelination of the injured nerve but also had a potent effect on neuropathic pain.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231167281"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/c2/10.1177_17590914231167281.PMC10475269.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10523566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Müller Glia to Müller Glia Extracellular Vesicle-Dependent Signaling Induces Multipotency Genes Nestin and lin28 Expression in Response to N-methyl-D-aspartate (NMDA) Exposure. 神经胶质瘤与神经胶质瘤细胞外囊泡依赖信号传导诱导NMDA暴露后多能基因Nestin和lin28的表达
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231183272
Ana Karen Carapia, Erick J Martinez-Colin, Deisy Segura-Villalobos, Rebeca Yael Victoria-Chavez, Ivonne Lezama, Eduardo Martinez-Martinez, Monica Lamas

Summary statement: Retinal Müller cells secrete extracellular vesicles that can be captured by other Müller cells. In response to a signal that may be deleterious for the retina, Müller glia-derived extracellular vesicles spread instructions to induce gene expression changes in other cells.

总结陈述:视网膜大网膜 ller细胞分泌细胞外囊泡,这些囊泡可以被其他大网膜 ller细胞捕获。作为对可能对视网膜有害的信号的反应,神经胶质来源的细胞外囊泡传播指令,诱导其他细胞的基因表达变化。
{"title":"Müller Glia to Müller Glia Extracellular Vesicle-Dependent Signaling Induces Multipotency Genes <i>Nestin</i> and l<i>in28</i> Expression in Response to N-methyl-D-aspartate (NMDA) Exposure.","authors":"Ana Karen Carapia,&nbsp;Erick J Martinez-Colin,&nbsp;Deisy Segura-Villalobos,&nbsp;Rebeca Yael Victoria-Chavez,&nbsp;Ivonne Lezama,&nbsp;Eduardo Martinez-Martinez,&nbsp;Monica Lamas","doi":"10.1177/17590914231183272","DOIUrl":"https://doi.org/10.1177/17590914231183272","url":null,"abstract":"<p><strong>Summary statement: </strong>Retinal Müller cells secrete extracellular vesicles that can be captured by other Müller cells. In response to a signal that may be deleterious for the retina, Müller glia-derived extracellular vesicles spread instructions to induce gene expression changes in other cells.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231183272"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/f4/10.1177_17590914231183272.PMC10291543.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The α2 Adrenoceptor Agonist and Sedative/Anaesthetic Dexmedetomidine Excites Diverse Neuronal Types in the Ventrolateral Preoptic Area of Male Mice. α2肾上腺素受体激动剂和镇静/麻醉用右美托咪定刺激雄性小鼠视前腹外侧区不同类型的神经元。
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231191016
Sumei Fan, Xinqi Cheng, Pingping Zhang, Yuanyin Wang, Liecheng Wang, Juan Cheng

Summary statement: Dexmedetomidine is an important ICU sedative. The mechanism of dexmedetomidine is not fully understood. Activating NA(-) and NA(+) neurons in the VLPO by dexmedetomidine using polysomnography and electrophysiological recording, this may explain the unique sedative properties with rapid arousal.

摘要:右美托咪定是一种重要的ICU镇静剂。右美托咪定的作用机制尚不完全清楚。右美托咪定通过多导睡眠图和电生理记录激活VLPO中的NA(-)和NA(+)神经元,这可能解释了快速唤醒的独特镇静特性。
{"title":"The α<sub>2</sub> Adrenoceptor Agonist and Sedative/Anaesthetic Dexmedetomidine Excites Diverse Neuronal Types in the Ventrolateral Preoptic Area of Male Mice.","authors":"Sumei Fan, Xinqi Cheng, Pingping Zhang, Yuanyin Wang, Liecheng Wang, Juan Cheng","doi":"10.1177/17590914231191016","DOIUrl":"10.1177/17590914231191016","url":null,"abstract":"<p><strong>Summary statement: </strong>Dexmedetomidine is an important ICU sedative. The mechanism of dexmedetomidine is not fully understood. Activating NA(-) and NA(+) neurons in the VLPO by dexmedetomidine using polysomnography and electrophysiological recording, this may explain the unique sedative properties with rapid arousal.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231191016"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/49/10.1177_17590914231191016.PMC10388635.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9909794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of the PACAP/PAC1 Signaling Pathway Accelerates the Repair of Impaired Spatial Memory Caused by an Ultradian Light Cycle. PACAP/PAC1信号通路的激活加速了超强光周期引起的空间记忆损伤的修复
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231169140
Dejiao Xu, Ying Zhang, Jun Feng, Hongyu Fu, Jiayi Li, Wei Wang, Zhen Li, Pingping Zhang, Xinqi Cheng, Liecheng Wang, Juan Cheng

The mechanism of light-induced spatial memory deficits, as well as whether rhythmic expression of the pituitary adenylyl cyclase-activating polypeptides (PACAP)-PAC1 pathway influenced by light is related to this process, remains unclear. Here, we aimed to investigate the role of the PACAP-PAC1 pathway in light-mediated spatial memory deficits. Animals were first housed under a T24 cycle (12 h light:12 h dark), and then light conditions were transformed to a T7 cycle (3.5 h light:3.5 h dark) for at least 4 weeks. The spatial memory function was assessed using the Morris water maze (MWM). In line with behavioral studies, rhythmic expression of the PAC1 receptor and glutamate receptors in the hippocampal CA1 region was assessed by western blotting, and electrophysiology experiments were performed to determine the influence of the PACAP-PAC1 pathway on neuronal excitability and synaptic signaling transmission. Spatial memory was deficient after mice were exposed to the T7 light cycle. Rhythmic expression of the PAC1 receptor was dramatically decreased, and the excitability of CA1 pyramidal cells was decreased in T7 cycle-housed mice. Compensation with PACAP1-38, a PAC1 receptor agonist, helped T7 cycle-housed mouse CA1 pyramidal cells recover neuronal excitability to normal levels, and cannulas injected with PACAP1-38 shortened the time to find the platform in MWM. Importantly, the T7 cycle decreased the frequency of AMPA receptor-mediated excitatory postsynaptic currents. In conclusion, the PACAP-PAC1 pathway is an important protective factor modulating light-induced spatial memory function deficits, affecting CA1 pyramidal cell excitability and excitatory synaptic signaling transmission.

光诱发空间记忆缺陷的机制,以及受光影响的垂体腺苷酸环化酶激活多肽(PACAP)-PAC1通路的节律性表达是否与这一过程有关,目前尚不清楚。在这里,我们旨在研究PACAP-PAC1通路在光介导的空间记忆缺陷中的作用。动物首先在T24周期(12小时光照:12小时黑暗)下饲养,然后将光照条件转换为T7周期(3.5小时光照:3.5小时黑暗)至少4周。采用Morris水迷宫(MWM)评价空间记忆功能。结合行为学研究,采用western blotting方法评估海马CA1区PAC1受体和谷氨酸受体的节律性表达,并通过电生理实验确定PACAP-PAC1通路对神经元兴奋性和突触信号传递的影响。T7光循环后小鼠空间记忆缺失。T7周期小鼠PAC1受体的节律性表达显著降低,CA1锥体细胞的兴奋性降低。用PAC1受体激动剂PACAP1-38进行补偿,有助于T7周期小鼠CA1锥体细胞的神经元兴奋性恢复到正常水平,注射PACAP1-38的套管缩短了在MWM中找到平台的时间。重要的是,T7周期降低了AMPA受体介导的兴奋性突触后电流的频率。综上所述,PACAP-PAC1通路是调节光致空间记忆功能缺陷的重要保护因子,影响CA1锥体细胞的兴奋性和兴奋性突触信号传递。
{"title":"Activation of the PACAP/PAC1 Signaling Pathway Accelerates the Repair of Impaired Spatial Memory Caused by an Ultradian Light Cycle.","authors":"Dejiao Xu,&nbsp;Ying Zhang,&nbsp;Jun Feng,&nbsp;Hongyu Fu,&nbsp;Jiayi Li,&nbsp;Wei Wang,&nbsp;Zhen Li,&nbsp;Pingping Zhang,&nbsp;Xinqi Cheng,&nbsp;Liecheng Wang,&nbsp;Juan Cheng","doi":"10.1177/17590914231169140","DOIUrl":"https://doi.org/10.1177/17590914231169140","url":null,"abstract":"<p><p>The mechanism of light-induced spatial memory deficits, as well as whether rhythmic expression of the pituitary adenylyl cyclase-activating polypeptides (PACAP)-PAC1 pathway influenced by light is related to this process, remains unclear. Here, we aimed to investigate the role of the PACAP-PAC1 pathway in light-mediated spatial memory deficits. Animals were first housed under a T24 cycle (12 h light:12 h dark), and then light conditions were transformed to a T7 cycle (3.5 h light:3.5 h dark) for at least 4 weeks. The spatial memory function was assessed using the Morris water maze (MWM). In line with behavioral studies, rhythmic expression of the PAC1 receptor and glutamate receptors in the hippocampal CA1 region was assessed by western blotting, and electrophysiology experiments were performed to determine the influence of the PACAP-PAC1 pathway on neuronal excitability and synaptic signaling transmission. Spatial memory was deficient after mice were exposed to the T7 light cycle. Rhythmic expression of the PAC1 receptor was dramatically decreased, and the excitability of CA1 pyramidal cells was decreased in T7 cycle-housed mice. Compensation with PACAP1-38, a PAC1 receptor agonist, helped T7 cycle-housed mouse CA1 pyramidal cells recover neuronal excitability to normal levels, and cannulas injected with PACAP1-38 shortened the time to find the platform in MWM. Importantly, the T7 cycle decreased the frequency of AMPA receptor-mediated excitatory postsynaptic currents. In conclusion, the PACAP-PAC1 pathway is an important protective factor modulating light-induced spatial memory function deficits, affecting CA1 pyramidal cell excitability and excitatory synaptic signaling transmission.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231169140"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/b4/10.1177_17590914231169140.PMC10123913.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hippocampus Insulin Receptors Regulate Episodic and Spatial Memory Through Excitatory/Inhibitory Balance. 海马胰岛素受体通过兴奋/抑制平衡调节情景和空间记忆。
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231206657
Cai-Yan Xue, Tian Gao, E Mao, Zhen-Zhen Kou, Ling Dong, Feng Gao

It is well known that the hippocampus is a vital brain region playing a key role in both episodic and spatial memory. Insulin receptors (InsRs) are densely distributed in the hippocampus and are important for its function. However, the effects of InsRs on the function of the specific hippocampal cell types remain elusive. In this study, hippocampal InsRs knockout mice had impaired episodic and spatial memory. GABAergic neurons and glutamatergic neurons in the hippocampus are involved in the balance between excitatory and inhibitory (E/I) states and participate in the processes of episodic and spatial memory. InsRs are located mainly at excitatory neurons in the hippocampus, whereas 8.5% of InsRs are glutamic acid decarboxylase 2 (GAD2)::Ai9-positive (GABAergic) neurons. Next, we constructed a transgenic mouse system in which InsR expression was deleted from GABAergic (glutamate decarboxylase 2::InsRfl/fl, GAD2Cre::InsRfl/fl) or glutamatergic neurons (vesicular glutamate transporter 2::InsRfl/fl,Vglut2Cre::InsRfl/fl). Our results showed that in comparison to the InsRfl/fl mice, both episodic and spatial memory were lower in GAD2Cre::InsRfl/fl and Vglut2Cre::InsRfl/fl. In addition, both GAD2Cre::InsRfl/fl and Vglut2Cre::InsRfl/fl were associated with more anxiety and lower glucose tolerance. These findings reveal that hippocampal InsRs might be crucial for episodic and spatial memory through E/I balance hippocampal regulation.

众所周知,海马体是大脑中至关重要的区域,在情景记忆和空间记忆中都发挥着关键作用。胰岛素受体(InsRs)密集分布在海马体中,对其功能很重要。然而,InsRs对特定海马细胞类型功能的影响仍然难以捉摸。在这项研究中,海马InsRs敲除小鼠的情景记忆和空间记忆受损。海马中的GABA能神经元和谷氨酸能神经元参与兴奋和抑制(E/I)状态之间的平衡,并参与情景记忆和空间记忆的过程。InsRs主要位于海马的兴奋性神经元,而8.5%的InsRs是谷氨酸脱羧酶2(GAD2)::Ai9阳性(GABA能)神经元。接下来,我们构建了一个转基因小鼠系统,其中InsR表达从GABA能神经元(谷氨酸脱羧酶2::InsRfl/fl,GAD2Cr::InsRfl/fl)或谷氨酸能神经元(囊泡谷氨酸转运体2::InsRfl/fl,Vglut2Cr::InsRfl/fl)中缺失。我们的研究结果表明,与InsRfl/fl小鼠相比,GAD2Cr::InsRfl/fl和Vglut2Cr::Insirfl/fl小鼠的情景记忆和空间记忆都较低。此外,GAD2Cr::InsRfl/fl和Vglut2Cr::Insirfl/fl都与更多的焦虑和更低的糖耐量有关。这些发现表明,海马InsRs可能通过E/I平衡海马调节对情景记忆和空间记忆至关重要。
{"title":"Hippocampus Insulin Receptors Regulate Episodic and Spatial Memory Through Excitatory/Inhibitory Balance.","authors":"Cai-Yan Xue, Tian Gao, E Mao, Zhen-Zhen Kou, Ling Dong, Feng Gao","doi":"10.1177/17590914231206657","DOIUrl":"10.1177/17590914231206657","url":null,"abstract":"<p><p>It is well known that the hippocampus is a vital brain region playing a key role in both episodic and spatial memory. Insulin receptors (InsRs) are densely distributed in the hippocampus and are important for its function. However, the effects of InsRs on the function of the specific hippocampal cell types remain elusive. In this study, hippocampal InsRs knockout mice had impaired episodic and spatial memory. GABAergic neurons and glutamatergic neurons in the hippocampus are involved in the balance between excitatory and inhibitory (E/I) states and participate in the processes of episodic and spatial memory. InsRs are located mainly at excitatory neurons in the hippocampus, whereas 8.5% of InsRs are glutamic acid decarboxylase 2 (GAD2)::Ai9-positive (GABAergic) neurons. Next, we constructed a transgenic mouse system in which InsR expression was deleted from GABAergic (glutamate decarboxylase 2::InsR<sup>fl/fl</sup>, GAD2<sup>Cre</sup>::InsR<sup>fl/fl</sup>) or glutamatergic neurons (vesicular glutamate transporter 2::InsR<sup>fl/fl</sup>,Vglut2<sup>Cre</sup>::InsR<sup>fl/fl</sup>). Our results showed that in comparison to the InsR<sup>fl/fl</sup> mice, both episodic and spatial memory were lower in GAD2<sup>Cre</sup>::InsR<sup>fl/fl</sup> and Vglut2<sup>Cre</sup>::InsR<sup>fl/fl</sup>. In addition, both GAD2<sup>Cre</sup>::InsR<sup>fl/fl</sup> and Vglut2<sup>Cre</sup>::InsR<sup>fl/fl</sup> were associated with more anxiety and lower glucose tolerance. These findings reveal that hippocampal InsRs might be crucial for episodic and spatial memory through E/I balance hippocampal regulation.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231206657"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice. 帕金森病模型小鼠中DNA损伤相关生物标志物的上调
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231152099
Fei Zeng, Karsten Parker, Yanqiang Zhan, Matthew Miller, Meng-Yang Zhu

Summary statement: The present study examined expression of DNA damage markers in VMAT2 Lo PD model mice. The results demonstrate there is a significant increase in these DNA damage markers mostly in the brain regions of 18- and 23-month-old model mice, indicating oxidative stress-induced DNA lesion is an important pathologic feature of this mouse model.

摘要:本研究检测了VMAT2 Lo PD模型小鼠DNA损伤标志物的表达。结果表明,这些DNA损伤标志物在18和23月龄模型小鼠的大脑区域显著增加,表明氧化应激诱导的DNA损伤是该模型小鼠的重要病理特征。
{"title":"Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice.","authors":"Fei Zeng, Karsten Parker, Yanqiang Zhan, Matthew Miller, Meng-Yang Zhu","doi":"10.1177/17590914231152099","DOIUrl":"10.1177/17590914231152099","url":null,"abstract":"<p><strong>Summary statement: </strong>The present study examined expression of DNA damage markers in VMAT2 Lo PD model mice. The results demonstrate there is a significant increase in these DNA damage markers mostly in the brain regions of 18- and 23-month-old model mice, indicating oxidative stress-induced DNA lesion is an important pathologic feature of this mouse model.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231152099"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/ad/10.1177_17590914231152099.PMC9880594.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10784089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advancements in a FRET Biosensor for Live-Cell Fluorescence-Lifetime High-Throughput Screening of Alpha-Synuclein. 用于α-突触核蛋白的活细胞荧光寿命高通量筛选的FRET生物传感器的进展。
IF 3.9 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231184086
Anthony R Braun, Noah Nathan Kochen, Samantha L Yuen, Elly E Liao, Razvan L Cornea, David D Thomas, Jonathan N Sachs

There is a critical need for small molecules capable of rescuing pathophysiological phenotypes induced by alpha-synuclein (aSyn) misfolding and oligomerization. Building upon our previous aSyn cellular fluorescence lifetime (FLT)-Förster resonance energy transfer (FRET) biosensors, we have developed an inducible cell model incorporating the red-shifted mCyRFP1/mMaroon1 (OFP/MFP) FRET pair. This new aSyn FRET biosensor improves the signal-to-noise ratio, reduces nonspecific background FRET, and results in a 4-fold increase (transient transfection) and 2-fold increase (stable, inducible cell lines) in FRET signal relative to our previous GFP/RFP aSyn biosensors. The inducible system institutes greater temporal control and scalability, allowing for fine-tuning of biosensor expression and minimizes cellular cytotoxicity due to overexpression of aSyn. Using these inducible aSyn-OFP/MFP biosensors, we screened the Selleck library of 2684 commercially available, FDA-approved compounds and identified proanthocyanidins and casanthranol as novel hits. Secondary assays validated the ability of these compounds to modulate aSyn FLT-FRET. Functional assays probing cellular cytotoxicity and aSyn fibrillization demonstrated their capability to inhibit seeded aSyn fibrillization. Proanthocyanidins completely rescued aSyn fibril-induced cellular toxicity with EC50 of 200 nM and casanthranol supported a 85.5% rescue with a projected EC50 of 34.2 μM. Furthermore, proanthocyanidins provide a valuable tool compound to validate our aSyn biosensor performance in future high-throughput screening campaigns of industrial-scale (million-compound) chemical libraries.

迫切需要能够拯救由α-突触核蛋白(aSyn)错误折叠和寡聚化诱导的病理生理表型的小分子。在我们之前的aSyn细胞荧光寿命(FLT)-Förster共振能量转移(FRET)生物传感器的基础上,我们开发了一种包含红移mCyRFP1/mMaroon1(OFP/MFP)FRET对的诱导型细胞模型。与我们以前的GFP/RFP-aSyn生物传感器相比,这种新的aSyn FRET生物传感器提高了信噪比,降低了非特异性背景FRET,并导致FRET信号增加了4倍(瞬时转染)和2倍(稳定、可诱导的细胞系)。诱导型系统具有更大的时间控制和可扩展性,允许生物传感器表达的微调,并最大限度地减少由于aSyn过表达引起的细胞毒性。使用这些可诱导的aSyn OFP/MFP生物传感器,我们筛选了2684种可商购的、经美国食品药品监督管理局批准的化合物的Selleck文库,并将原花青素和casanthranol鉴定为新的命中物。二次测定验证了这些化合物调节aSyn FLT-FRET的能力。检测细胞细胞毒性和aSyn原纤维化的功能测定证明了它们抑制种子aSyn原纤化的能力。原花青素以200的EC50完全挽救了aSyn原纤维诱导的细胞毒性 nM和casanthranol支持85.5%的挽救,预计EC50为34.2 μM。此外,原花青素提供了一种有价值的工具化合物,可以在未来工业规模(百万化合物)化学文库的高通量筛选活动中验证我们的aSyn生物传感器的性能。
{"title":"Advancements in a FRET Biosensor for Live-Cell Fluorescence-Lifetime High-Throughput Screening of Alpha-Synuclein.","authors":"Anthony R Braun, Noah Nathan Kochen, Samantha L Yuen, Elly E Liao, Razvan L Cornea, David D Thomas, Jonathan N Sachs","doi":"10.1177/17590914231184086","DOIUrl":"10.1177/17590914231184086","url":null,"abstract":"<p><p>There is a critical need for small molecules capable of rescuing pathophysiological phenotypes induced by alpha-synuclein (aSyn) misfolding and oligomerization. Building upon our previous aSyn cellular fluorescence lifetime (FLT)-Förster resonance energy transfer (FRET) biosensors, we have developed an inducible cell model incorporating the red-shifted mCyRFP1/mMaroon1 (OFP/MFP) FRET pair. This new aSyn FRET biosensor improves the signal-to-noise ratio, reduces nonspecific background FRET, and results in a 4-fold increase (transient transfection) and 2-fold increase (stable, inducible cell lines) in FRET signal relative to our previous GFP/RFP aSyn biosensors. The inducible system institutes greater temporal control and scalability, allowing for fine-tuning of biosensor expression and minimizes cellular cytotoxicity due to overexpression of aSyn. Using these inducible aSyn-OFP/MFP biosensors, we screened the Selleck library of 2684 commercially available, FDA-approved compounds and identified proanthocyanidins and casanthranol as novel hits. Secondary assays validated the ability of these compounds to modulate aSyn FLT-FRET. Functional assays probing cellular cytotoxicity and aSyn fibrillization demonstrated their capability to inhibit seeded aSyn fibrillization. Proanthocyanidins completely rescued aSyn fibril-induced cellular toxicity with EC<sub>50</sub> of 200 nM and casanthranol supported a 85.5% rescue with a projected EC<sub>50</sub> of 34.2 μM. Furthermore, proanthocyanidins provide a valuable tool compound to validate our aSyn biosensor performance in future high-throughput screening campaigns of industrial-scale (million-compound) chemical libraries.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231184086"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/09/10.1177_17590914231184086.PMC10338669.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diazepam Binding Inhibitor Control of Eu- and Hypoglycemic Patterns of Ventromedial Hypothalamic Nucleus Glucose-Regulatory Signaling. 地西泮结合抑制剂控制下丘脑腹内侧核葡萄糖调节信号的Eu-和低血糖模式。
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231214116
Sagor C Roy, Subash Sapkota, Madhu Babu Pasula, Khaggeswar Bheemanapally, Karen P Briski

Pharmacological stimulation/antagonism of astrocyte glio-peptide octadecaneuropeptide signaling alters ventromedial hypothalamic nucleus (VMN) counterregulatory γ-aminobutyric acid (GABA) and nitric oxide transmission. The current research used newly developed capillary zone electrophoresis-mass spectrometry methods to investigate hypoglycemia effects on VMN octadecaneuropeptide content, along with gene knockdown tools to determine if octadecaneuropeptide signaling regulates these transmitters during eu- and/or hypoglycemia. Hypoglycemia caused dissimilar adjustments in the octadecaneuropeptide precursor, i.e., diazepam-binding-inhibitor and octadecaneuropeptide levels in dorsomedial versus ventrolateral VMN. Intra-VMN diazepam-binding-inhibitor siRNA administration decreased baseline 67 and 65 kDa glutamate decarboxylase mRNA levels in GABAergic neurons laser-microdissected from each location, but only affected hypoglycemic transcript expression in ventrolateral VMN. This knockdown therapy imposed dissimilar effects on eu- and hypoglycemic glucokinase and 5'-AMP-activated protein kinase-alpha1 (AMPKα1) and -alpha2 (AMPKα2) gene profiles in dorsomedial versus ventrolateral GABAergic neurons. Diazepam-binding-inhibitor gene silencing up-regulated baseline (dorsomedial) or hypoglycemic (ventrolateral) nitrergic neuron neuronal nitric oxide synthase mRNA profiles. Baseline nitrergic cell glucokinase mRNA was up- (ventrolateral) or down- (dorsomedial) regulated by diazepam-binding-inhibitor siRNA, but knockdown enhanced hypoglycemic profiles in both sites. Nitrergic nerve cell AMPKα1 and -α2 transcripts exhibited division-specific responses to this genetic manipulation during eu- and hypoglycemia. Results document the utility of capillary zone electrophoresis-mass spectrometric tools for quantification of ODN in small-volume brain tissue samples. Data show that hypoglycemia has dissimilar effects on ODN signaling in the two major neuroanatomical divisions of the VMN and that this glio-peptide imposes differential control of glucose-regulatory neurotransmission in the VMNdm versus VMNvl during eu- and hypoglycemia.

星形胶质肽信号通路的药理刺激/拮抗改变下丘脑腹内侧核(VMN)对γ-氨基丁酸(GABA)和一氧化氮传递的拮抗作用。目前的研究使用新开发的毛细管区带电泳-质谱方法来研究低血糖对VMN octadecaneuropeptide含量的影响,并使用基因敲低工具来确定octadecaneuropeptide信号是否在eu和/或低血糖期间调节这些递质。低血糖引起十八能欧肽前体的不同调整,即地西泮结合抑制剂和十八能欧肽水平在背内侧和腹外侧VMN中。VMN内给药地西帕-结合抑制剂siRNA降低了激光显微解剖的gaba能神经元67和65 kDa谷氨酸脱羧酶mRNA的基线水平,但仅影响腹侧VMN中低血糖转录物的表达。这种低敲疗法对背内侧和腹外侧gaba能神经元中eu-和低血糖葡萄糖激酶以及5'- amp活化蛋白激酶- α1 (AMPKα1)和- α2 (AMPKα2)基因谱的影响不同。地西泮结合抑制剂基因沉默上调的基线(背内侧)或低血糖(腹外侧)氮能神经元神经元一氧化氮合酶mRNA谱。基线氮能细胞葡萄糖激酶mRNA受地西泮结合抑制剂siRNA的上调(腹外侧)或下调(背内侧)调节,但下调这两个位点的低血糖谱增强。在低血糖和低血糖时,氮神经细胞AMPKα1和-α2转录物对这种基因操作表现出分裂特异性反应。结果证明毛细管区带电泳-质谱工具用于定量小体积脑组织样品中的ODN。数据显示,低血糖对VMN的两个主要神经解剖分区的ODN信号传导有不同的影响,并且这种胶质肽在低血糖和低血糖期间对VMNdm和VMNvl中葡萄糖调节神经传递施加不同的控制。
{"title":"Diazepam Binding Inhibitor Control of Eu- and Hypoglycemic Patterns of Ventromedial Hypothalamic Nucleus Glucose-Regulatory Signaling.","authors":"Sagor C Roy, Subash Sapkota, Madhu Babu Pasula, Khaggeswar Bheemanapally, Karen P Briski","doi":"10.1177/17590914231214116","DOIUrl":"10.1177/17590914231214116","url":null,"abstract":"<p><p>Pharmacological stimulation/antagonism of astrocyte glio-peptide octadecaneuropeptide signaling alters ventromedial hypothalamic nucleus (VMN) counterregulatory γ-aminobutyric acid (GABA) and nitric oxide transmission. The current research used newly developed capillary zone electrophoresis-mass spectrometry methods to investigate hypoglycemia effects on VMN octadecaneuropeptide content, along with gene knockdown tools to determine if octadecaneuropeptide signaling regulates these transmitters during eu- and/or hypoglycemia. Hypoglycemia caused dissimilar adjustments in the octadecaneuropeptide precursor, i.e., diazepam-binding-inhibitor and octadecaneuropeptide levels in dorsomedial versus ventrolateral VMN. Intra-VMN diazepam-binding-inhibitor siRNA administration decreased baseline 67 and 65 kDa glutamate decarboxylase mRNA levels in GABAergic neurons laser-microdissected from each location, but only affected hypoglycemic transcript expression in ventrolateral VMN. This knockdown therapy imposed dissimilar effects on eu- and hypoglycemic glucokinase and 5'-AMP-activated protein kinase-alpha1 (AMPKα1) and -alpha2 (AMPKα2) gene profiles in dorsomedial versus ventrolateral GABAergic neurons. Diazepam-binding-inhibitor gene silencing up-regulated baseline (dorsomedial) or hypoglycemic (ventrolateral) nitrergic neuron neuronal nitric oxide synthase mRNA profiles. Baseline nitrergic cell glucokinase mRNA was up- (ventrolateral) or down- (dorsomedial) regulated by diazepam-binding-inhibitor siRNA, but knockdown enhanced hypoglycemic profiles in both sites. Nitrergic nerve cell AMPKα1 and -α2 transcripts exhibited division-specific responses to this genetic manipulation during eu- and hypoglycemia. Results document the utility of capillary zone electrophoresis-mass spectrometric tools for quantification of ODN in small-volume brain tissue samples. Data show that hypoglycemia has dissimilar effects on ODN signaling in the two major neuroanatomical divisions of the VMN and that this glio-peptide imposes differential control of glucose-regulatory neurotransmission in the VMNdm versus VMNvl during eu- and hypoglycemia.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231214116"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SOD1G93A Astrocyte-Derived Extracellular Vesicles Induce Motor Neuron Death by a miRNA-155-5p-Mediated Mechanism. SOD1G93A星形细胞衍生的细胞外小泡通过miRNA-155-5p介导的机制诱导运动神经元死亡。
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231197527
Soledad Marton, Ernesto Miquel, Joaquín Acosta-Rodríguez, Santiago Fontenla, Gabriela Libisch, Patricia Cassina

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by upper and lower motor neuron (MN) degeneration. Astrocytes surrounding MNs are known to modulate ALS progression. When cocultured with astrocytes overexpressing the ALS-linked mutant Cu/Zn superoxide dismutase (SOD1G93A) or when cultured with conditioned medium from SOD1G93A astrocytes, MN survival is reduced. The exact mechanism of this neurotoxic effect is unknown. Astrocytes secrete extracellular vesicles (EVs) that transport protein, mRNA, and microRNA species from one cell to another. The size and protein markers characteristic of exosomes were observed in the EVs obtained from cultured astrocytes, indicating their abundance in exosomes. Here, we analyzed the microRNA content of the exosomes derived from SOD1G93A astrocytes and evaluated their role in MN survival. Purified MNs exposed to SOD1G93A astrocyte-derived exosomes showed reduced survival and neurite length compared to those exposed to exosomes derived from non-transgenic (non-Tg) astrocytes. Analysis of the miRNA content of the exosomes revealed that miR-155-5p and miR-582-3p are differentially expressed in SOD1G93A exosomes compared with exosomes from non-Tg astrocytes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicates that miR-155-5p and miR-582-3p predicted targets are enriched in the neurotrophin signaling pathway. Importantly, when levels of miR-155-5p were reduced by incubation with a specific antagomir, SOD1G93A exosomes did not affect MN survival or neurite length. These results demonstrate that SOD1G93A-derived exosomes are sufficient to induce MN death, and miRNA-155-5p contributes to this effect. miRNA-155-5p may offer a new therapeutic target to modulate disease progression in ALS.

肌萎缩侧索硬化症(ALS)是一种以上下运动神经元(MN)变性为特征的致命性神经退行性疾病。已知MN周围的星形胶质细胞可调节ALS的进展。当与过表达ALS连接的突变体Cu/Zn超氧化物歧化酶(SOD1G93A)的星形胶质细胞共培养时,或当与来自SOD1G93A-星形胶质细胞的条件培养基培养时,MN存活率降低。这种神经毒性作用的确切机制尚不清楚。星形胶质细胞分泌细胞外小泡(EVs),将蛋白质、mRNA和微小RNA物质从一个细胞运输到另一个细胞。在从培养的星形胶质细胞获得的EVs中观察到外泌体的大小和蛋白质标记特征,表明它们在外泌体中的丰度。在这里,我们分析了来源于SOD1G93A星形胶质细胞的外泌体的微小RNA含量,并评估了它们在MN存活中的作用。与暴露于衍生自非转基因(非Tg)星形胶质细胞的外泌体的MN相比,暴露于SOD1G93A星形胶质细胞衍生的外泌物的纯化MN显示出降低的存活率和轴突长度。对外泌体的miRNA含量的分析显示,与来自非Tg星形胶质细胞的外泌体相比,miR-155-5p和miR-582-3p在SOD1G93A外泌体中差异表达。京都基因和基因组百科全书(KEGG)分析表明,miR-155-5p和miR-582-3p预测的靶标在神经营养因子信号通路中富集。重要的是,当miR-155-5p的水平通过与特异性抗病毒药物孵育而降低时,SOD1G93A外泌体不会影响MN的存活率或轴突长度。这些结果表明,SOD1G93A衍生的外泌体足以诱导MN死亡,并且miRNA-155-5p有助于这种作用。miRNA-155-5p可能提供一种新的治疗靶点来调节ALS的疾病进展。
{"title":"SOD1<sup>G93A</sup> Astrocyte-Derived Extracellular Vesicles Induce Motor Neuron Death by a miRNA-155-5p-Mediated Mechanism.","authors":"Soledad Marton, Ernesto Miquel, Joaquín Acosta-Rodríguez, Santiago Fontenla, Gabriela Libisch, Patricia Cassina","doi":"10.1177/17590914231197527","DOIUrl":"10.1177/17590914231197527","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by upper and lower motor neuron (MN) degeneration. Astrocytes surrounding MNs are known to modulate ALS progression. When cocultured with astrocytes overexpressing the ALS-linked mutant Cu/Zn superoxide dismutase (SOD1<sup>G93A</sup>) or when cultured with conditioned medium from SOD1<sup>G93A</sup> astrocytes, MN survival is reduced. The exact mechanism of this neurotoxic effect is unknown. Astrocytes secrete extracellular vesicles (EVs) that transport protein, mRNA, and microRNA species from one cell to another. The size and protein markers characteristic of exosomes were observed in the EVs obtained from cultured astrocytes, indicating their abundance in exosomes. Here, we analyzed the microRNA content of the exosomes derived from SOD1<sup>G93A</sup> astrocytes and evaluated their role in MN survival. Purified MNs exposed to SOD1<sup>G93A</sup> astrocyte-derived exosomes showed reduced survival and neurite length compared to those exposed to exosomes derived from non-transgenic (non-Tg) astrocytes. Analysis of the miRNA content of the exosomes revealed that miR-155-5p and miR-582-3p are differentially expressed in SOD1<sup>G93A</sup> exosomes compared with exosomes from non-Tg astrocytes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicates that miR-155-5p and miR-582-3p predicted targets are enriched in the neurotrophin signaling pathway. Importantly, when levels of miR-155-5p were reduced by incubation with a specific antagomir, SOD1<sup>G93A</sup> exosomes did not affect MN survival or neurite length. These results demonstrate that SOD1<sup>G93A</sup>-derived exosomes are sufficient to induce MN death, and miRNA-155-5p contributes to this effect. miRNA-155-5p may offer a new therapeutic target to modulate disease progression in ALS.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231197527"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/10/10.1177_17590914231197527.PMC10467309.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polymorphisms in TPT1 Pathways in Pediatric Astrocytomas. 儿童星形细胞瘤中TPT1通路的多态性。
IF 4.7 4区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-01 DOI: 10.1177/17590914231153481
Eduardo Morais de Castro, Leonardo Vinícius Barbosa, Aline Simoneti Fonseca, Seigo Nagashima, Caroline Busatta Vaz de Paula, Rafaela Zeni, Letícia Arianne Panini do Carmo, Luciane R Cavalli, Luiz Fernando Bleggi Torres, Andrea Senff Ribeiro, Lucia de Noronha, Cleber Machado-Souza

Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 (TPT1) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR, MDM2, TP53, and CDKN1A, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas (p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared (p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma (p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.

中枢神经系统肿瘤,尤其是星形细胞瘤,是儿童期发病率和死亡率最高的实体肿瘤。诊断是基于组织病理学特征,但分子方法已越来越多地使用。翻译控制肿瘤蛋白(translation - controlled tumor protein, TCTP)是由肿瘤蛋白翻译控制1 (translation - controlled 1, TPT1)基因编码的一种多功能蛋白,在细胞周期中具有重要的生理作用。该蛋白的表达与几种肿瘤有关,包括成人的星形细胞瘤。然而,这种蛋白在儿童星形细胞瘤中的作用在很大程度上是未知的。我们的目的是评估在儿童星形细胞瘤病例中,在福尔马林固定石蜡包埋(FFPE)样本中,TPT1基因和其他与其分子通路相关的基因(如MTOR、MDM2、TP53和CDKN1A)的多态性频率,以及其与蛋白质表达和临床变量的相关性。这些样本进行基因分型和免疫组织化学分析。最具揭示性的结果是MDM2基因rs117039649 [G/C],其中C多态性等位基因仅在胶质母细胞瘤中存在(p = 0.028)。CDKN1A基因rs3176334 [T/C]仅在高级别星形细胞瘤中呈现纯合多态性基因型(p = 0.039)。胶质母细胞瘤患者细胞质MDM2的免疫组织化学表达与更高的生存率相关(p = 0.018)。MDM2和CDKN1A基因多态性的存在,以及MDM2表达之间的特定相关性,表明可能与儿童星形细胞瘤的风险相关。本研究寻求TCTP通路和相关蛋白在儿童星形细胞瘤发生中的可能作用,其中一些可能作为这些患者的预后标志物具有潜在影响。
{"title":"Polymorphisms in <i>TPT1</i> Pathways in Pediatric Astrocytomas.","authors":"Eduardo Morais de Castro,&nbsp;Leonardo Vinícius Barbosa,&nbsp;Aline Simoneti Fonseca,&nbsp;Seigo Nagashima,&nbsp;Caroline Busatta Vaz de Paula,&nbsp;Rafaela Zeni,&nbsp;Letícia Arianne Panini do Carmo,&nbsp;Luciane R Cavalli,&nbsp;Luiz Fernando Bleggi Torres,&nbsp;Andrea Senff Ribeiro,&nbsp;Lucia de Noronha,&nbsp;Cleber Machado-Souza","doi":"10.1177/17590914231153481","DOIUrl":"https://doi.org/10.1177/17590914231153481","url":null,"abstract":"<p><p>Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 (<i>TPT1</i>) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the <i>TPT1</i> gene and other genes associated with its molecular pathways, such as <i>MTOR</i>, <i>MDM2</i>, <i>TP53</i>, and <i>CDKN1A</i>, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the <i>MDM2</i> gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas (<i>p </i>= .028). The <i>CDKN1A</i> gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared (<i>p </i>= .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma (<i>p = </i>.018). The presence of polymorphisms in the <i>MDM2</i> and <i>CDKN1A</i> genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231153481"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/32/10.1177_17590914231153481.PMC9903018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10725456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
ASN NEURO
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1