Neurochemistry international最新文献_第4页

Apelin regulates mitochondrial dynamics by inhibiting Mst1-JNK-Drp1 signaling pathway to reduce neuronal apoptosis after spinal cord injury Apelin通过抑制Mst1-JNK-Drp1信号通路调节线粒体动力学，从而减少脊髓损伤后的神经细胞凋亡。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-19 DOI: 10.1016/j.neuint.2024.105885

Qixuan Guo , Qing Liu , Shuai Zhou , Yabin Lin , Ang Lv , Luping Zhang , Liming Li , Fei Huang

{"title":"Apelin regulates mitochondrial dynamics by inhibiting Mst1-JNK-Drp1 signaling pathway to reduce neuronal apoptosis after spinal cord injury","authors":"Qixuan Guo , Qing Liu , Shuai Zhou , Yabin Lin , Ang Lv , Luping Zhang , Liming Li , Fei Huang","doi":"10.1016/j.neuint.2024.105885","DOIUrl":"10.1016/j.neuint.2024.105885","url":null,"abstract":"<div><div>In the secondary injury stage of spinal cord injury, mitochondrial dysfunction leads to decreased ATP production, increased ROS production, and activation of the mitochondria-mediated apoptosis signaling pathway. This ultimately intensifies neuronal death and promotes the progression of the injury. Apelin, a peptide produced by the APLN gene, has demonstrated promise in the treatment of spinal cord injury. The aim of this study was to investigate how Apelin protects neurons after spinal cord injury by influencing the mitochondrial dynamics. The results showed that Apelin has the ability to reduce mitochondrial fission, enhance the mitochondrial membrane potential, improve antioxidant capacity, facilitate the clearance of excess ROS, and ultimately decrease apoptosis in PC12 cells. Moreover, Apelin is overexpressed in neurons in the damaged part of the spinal cord, contributing to reduce mitochondrial fission, improve antioxidant capacity, increase ATP production, decrease apoptosis, promote spinal cord morphological repair, maintain the number of nissl bodies, and enhance signal transduction in the descending spinal cord pathway. Apelin exerts its protective effect by inhibiting the Mst1-JNK-Drp1 signaling pathway. In summary, our study further improved the effect of Apelin in the treatment of spinal cord injury, revealed the mechanism of Apelin in protecting damaged neurons after spinal cord injury by maintaining mitochondrial homeostasis, and provided a new therapeutic mechanism for Apelin in spinal cord injury.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105885"},"PeriodicalIF":4.4,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Ras, RhoA, and vascular pharmacology in neurodevelopment and aging 神经发育和衰老中的 Ras、RhoA 和血管药理学。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-18 DOI: 10.1016/j.neuint.2024.105883

Ruth Nussinov , Hyunbum Jang , Feixiong Cheng

{"title":"Ras, RhoA, and vascular pharmacology in neurodevelopment and aging","authors":"Ruth Nussinov , Hyunbum Jang , Feixiong Cheng","doi":"10.1016/j.neuint.2024.105883","DOIUrl":"10.1016/j.neuint.2024.105883","url":null,"abstract":"<div><div>Small GTPases Ras, Rac, and RhoA are crucial regulators of cellular functions. They also act in dysregulated cell proliferation and transformation. Multiple publications have focused on illuminating their roles and mechanisms, including in immune system pathologies. Their functions in neurology-related diseases, neurodegeneration and neurodevelopment, are also emerging, as well as their potential as pharmacological targets in both pathologies. Observations increasingly suggest that these pathologies may relate to activation (or suppression) of signaling by members of the Ras superfamily, especially Ras, Rho, and Rac isoforms, and components of their signaling pathways. Germline (or embryonic) mutations that they harbor are responsible for neurodevelopmental disorders, such as RASopathies, autism spectrum disorder, and dilated cardiomyopathy. In aging, they promote neurodegenerative diseases, with Rho GTPase featuring in their pharmacology, as in the case of Alzheimer's disease (AD). Significantly, drugs with observed anti-AD activity, particularly those involved in cardiovascular systems, are associated with the RhoA signaling, as well as cerebral vasculature in brain development and aging. This leads us to suggest that anti-AD drugs could inform neurodevelopmental disorders, including pediatric low-grade gliomas pharmacology. Neurodevelopmental disorders associated with RhoA, like autism, are also connected with vascular systems, thus could be targets of vascular system-connected drugs.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105883"},"PeriodicalIF":4.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

LASP1 in the nucleus accumbens modulates methamphetamine-induced conditioned place preference in mice 小鼠伏隔核中的 LASP1 可调节甲基苯丙胺诱导的条件性位置偏好。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-16 DOI: 10.1016/j.neuint.2024.105884

Meng-Qing Li , Xiao-Yu Lu , Jia-Yu Yao , Guang-Jing Zou , Ze-Hao Zeng , Lin-Xuan Zhang , Shi-Fen Zhou , Zhao-Rong Chen , Tian-Shu Zhao , Zi-Rui Guo , Yan-Hui Cui , Fang Li , Chang-Qi Li

{"title":"LASP1 in the nucleus accumbens modulates methamphetamine-induced conditioned place preference in mice","authors":"Meng-Qing Li , Xiao-Yu Lu , Jia-Yu Yao , Guang-Jing Zou , Ze-Hao Zeng , Lin-Xuan Zhang , Shi-Fen Zhou , Zhao-Rong Chen , Tian-Shu Zhao , Zi-Rui Guo , Yan-Hui Cui , Fang Li , Chang-Qi Li","doi":"10.1016/j.neuint.2024.105884","DOIUrl":"10.1016/j.neuint.2024.105884","url":null,"abstract":"<div><div>Methamphetamine (METH) is a highly addictive and widely abused drug that causes complex adaptive changes in the brain's reward system, such as the nucleus accumbens (NAc). LASP1 (LIM and SH 3 domain protein 1) as an actin-binding protein, regulates synaptic plasticity. However, the role and mechanism by which NAc LASP1 contributes to METH addiction remains unclear. In this study, adult male C57BL/6J mice underwent repeated METH exposure or METH-induced conditioned place preference (CPP). Western blotting and immunohistochemistry were used to determine LASP1 expression in the NAc. Furthermore, LASP1 knockdown or overexpression using adeno-associated virus (AAV) administration via stereotactic injection into the NAc was used to observe the corresponding effects on CPP. We found that repeated METH exposure and METH-induced CPP upregulated LASP1 expression in the NAc. LASP1 silencing in the NAc reversed METH-induced CPP and reduced PSD95, NR2A, and NR2B expression, whereas LASP1 overexpression in the NAc enhanced CPP acquisition, accompanied by increased PSD95, NR2A, and NR2B expression. Our findings demonstrate an important role of NAc LASP1 in modulating METH induced drug-seeking behavior and the underlying mechanism may be related to regulate the expression of synapse-associated proteins in the NAc. These results reveal a novel molecular regulator of the actions of METH on the NAc and provide a new strategy for treating METH addiction.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105884"},"PeriodicalIF":4.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Changes in reactive oxygen species and autofluorescence under hypoxia at the hippocampal CA3 area: Role of calcium and zinc influxes 缺氧条件下海马 CA3 区活性氧和自发荧光的变化：钙和锌流入的作用

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-15 DOI: 10.1016/j.neuint.2024.105882

João L. Alves , Patrícia M. Reis , Rosa M. Quinta-Ferreira , M. Emília Quinta-Ferreira , Carlos M. Matias

{"title":"Changes in reactive oxygen species and autofluorescence under hypoxia at the hippocampal CA3 area: Role of calcium and zinc influxes","authors":"João L. Alves , Patrícia M. Reis , Rosa M. Quinta-Ferreira , M. Emília Quinta-Ferreira , Carlos M. Matias","doi":"10.1016/j.neuint.2024.105882","DOIUrl":"10.1016/j.neuint.2024.105882","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) have an important role in cellular biology, being involved, in a way that depends on their levels, in cell signaling processes or in oxidative stress, probably associated with neurodegenerative and other diseases. Most of the studies about ROS formation were performed in ischemic conditions, and thus, there is limited knowledge about ROS formation in less severe hypoxic conditions. This study investigates neuronal ROS generation and autofluorescence changes in hypoxic conditions, focusing on the involvement of calcium and zinc. Using hippocampal slices from Wistar rats, ROS production was monitored by the permeant fluorescent indicator H<sub>2</sub>DCFDA under different oxygenation levels. Moderate hypoxia (40% O<sub>2</sub>) led to a small ROS increase, while severe hypoxia (0% O<sub>2</sub>) showed a more pronounced rise. KCl-induced depolarization significantly enhanced ROS formation, particularly under severe hypoxia. Inhibition of NMDA receptors reduced ROS generation without affecting autofluorescence, while chelation of zinc ions decreased ROS production and increased flavin adenine dinucleotide (FAD) autofluorescence. These findings suggest that, in hypoxic conditions, ROS formation is mediated by calcium entry through NMDA receptors and also by zinc influxes. Thus, these ions play a crucial role in oxidative stress, which may be related with neurodegenerative diseases associated with ROS dysregulation.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105882"},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

MRPL41, as a target for acupuncture, promotes neuron apoptosis in models of ischemic stroke via activating p53 pathway 作为针灸靶点的MRPL41可通过激活p53通路促进缺血性中风模型中神经元的凋亡。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-13 DOI: 10.1016/j.neuint.2024.105881

Hong Guo , Yuanwei Dong , Danqing Luo , Meng Gong , Jianfeng Sun , Zhipeng Wu , Zhixiang Liu , Lei Zhong , Song Jin

{"title":"MRPL41, as a target for acupuncture, promotes neuron apoptosis in models of ischemic stroke via activating p53 pathway","authors":"Hong Guo , Yuanwei Dong , Danqing Luo , Meng Gong , Jianfeng Sun , Zhipeng Wu , Zhixiang Liu , Lei Zhong , Song Jin","doi":"10.1016/j.neuint.2024.105881","DOIUrl":"10.1016/j.neuint.2024.105881","url":null,"abstract":"<div><div>Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. <em>In vivo</em>, MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105881"},"PeriodicalIF":4.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The pivotal role of PACAP/PAC1R signaling from the anterior insular cortex to the locus coeruleus on anxiety-related behaviors of mice PACAP/PAC1R信号从前部岛叶皮层传导至小鼠神经节对小鼠焦虑相关行为的关键作用

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-11 DOI: 10.1016/j.neuint.2024.105879

Thi Thu Nguyen , Kohei Hashiguchi , James A. Waschek , Atsuro Miyata , Yuki Kambe

{"title":"The pivotal role of PACAP/PAC1R signaling from the anterior insular cortex to the locus coeruleus on anxiety-related behaviors of mice","authors":"Thi Thu Nguyen , Kohei Hashiguchi , James A. Waschek , Atsuro Miyata , Yuki Kambe","doi":"10.1016/j.neuint.2024.105879","DOIUrl":"10.1016/j.neuint.2024.105879","url":null,"abstract":"<div><div>The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific receptor (PAC1R) are widely present in the central nervous system (CNS), and PACAP/PAC1R signaling has been implicated in anxiety-related behaviors. The locus coeruleus (LC), with its extensive noradrenergic (NA) projections throughout the CNS, is also implicated in anxiety. Although the LC exhibits a high expression of PAC1R, the precise role of PACAP/PAC1R signaling in the LC's involvement in anxiety remains unclear. Histochemical analysis confirmed high levels of PAC1R mRNA in the LC and showed that PAC1R gene transcripts were highly localized to NA neurons. Targeted deletion of PAC1R from these cells led to a hyperactive/low anxiety phenotype in the open field and elevated-plus maze tests. Retrograde neurocircuit tracing indicated PACAP neurons from the anterior insular cortex (aIC) and a few other regions projected axons to the LC. The selective activation of PACAP neurons in the aIC led to significantly increased anxiety behavior without a change in overall locomotor activity. Moreover, shRNA PACAP knockdown in the aIC in wild-type mice led to a selective decrease in anxiety. The present results identify an aIC to LC neurocircuit controlling anxiety that critically requires PACAP/PAC1R signaling.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105879"},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Protein aggregation and its affecting mechanisms in neurodegenerative diseases 神经退行性疾病中的蛋白质聚集及其影响机制

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-11 DOI: 10.1016/j.neuint.2024.105880

Junyun Wu , Jianan Wu , Tao Chen , Jing Cai , Reng Ren

{"title":"Protein aggregation and its affecting mechanisms in neurodegenerative diseases","authors":"Junyun Wu , Jianan Wu , Tao Chen , Jing Cai , Reng Ren","doi":"10.1016/j.neuint.2024.105880","DOIUrl":"10.1016/j.neuint.2024.105880","url":null,"abstract":"<div><div>Protein aggregation serves as a critical pathological marker in a spectrum of neurodegenerative diseases (NDs), including the formation of amyloid β (Aβ) and Tau neurofibrillary tangles in Alzheimer's disease, as well as α-Synuclein (α-Syn) aggregates in Parkinson's disease, Parkinson's disease-related dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). A significant proportion of patients with amyotrophic lateral sclerosis (ALS) exhibit TDP-43 aggregates. Moreover, a confluence of brain protein pathologies, such as Aβ, Tau, α-Syn, and TDP-43, has been identified in individual NDs cases, highlighting the intricate interplay among these proteins that is garnering heightened scrutiny. Importantly, protein aggregation is modulated by an array of factors, with burgeoning evidence suggesting that it frequently results from perturbations in protein homeostasis, influenced by the cellular membrane milieu, metal ion concentrations, post-translational modifications, and genetic mutations. This review delves into the pathological underpinnings of protein aggregation across various NDs and elucidates the intercommunication among disparate proteins within the same disease context. Additionally, we examine the pathogenic mechanisms by which diverse factors impinge upon protein aggregation, offering fresh perspectives for the future therapeutic intervention of NDs.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105880"},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Olfactory dysfunction decreased local field potential in the reward system and increased EtOH consumption in mice 嗅觉功能障碍会降低奖赏系统的局部场电位，增加小鼠的乙醇消耗量。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-09 DOI: 10.1016/j.neuint.2024.105875

Jianhong Zhou , Di Luo , Yingjie An , Yuan Gao , Jichuan Zhang , Yanmei Chen

{"title":"Olfactory dysfunction decreased local field potential in the reward system and increased EtOH consumption in mice","authors":"Jianhong Zhou , Di Luo , Yingjie An , Yuan Gao , Jichuan Zhang , Yanmei Chen","doi":"10.1016/j.neuint.2024.105875","DOIUrl":"10.1016/j.neuint.2024.105875","url":null,"abstract":"<div><div>The relationship between olfactory dysfunction and alcohol intake is unobvious. Chronic alcohol intake results in reduced olfactory acuity and olfactory discrimination and addiction in humans. However, alcohol is a beverage with distinctive odors, which usually works as a cue to induce addictive memories and craving behavior. Whether olfactory impairment increase or decrease alcohol consumption remains an important but unclear issue. In this study, we measured ethanol (EtOH) consumption in the two-bottle choice EtOH drinking test, two bottle choice EtOH/sucrose drinking test and the drinking in the dark (DID) test during the olfactory loss. We also recorded local field potentials (LFPs) from the brain reward system, the ventral tegmental area (VTA), nucleus accumbens (NAc), and piriform cortex (Pir) one and four weeks after the induction of olfactory epithelium lesions using zinc sulfate (ZnSO<sub>4</sub>) in mice. The results showed that the EtOH consumption and preference were increased during the period of olfactory dysfunction. 1 week after the olfactory injury, LFP powers in the reward system at low- and high-gamma bands decreased significantly, coherence between the Pir and the reward system was also decrease. 4 weeks after the ZnSO<sub>4</sub> treatment, LFP powers were reversed, but the coherence between VTA and NAc was decreased, indicating lasting effects post-recovery. This study demonstrates that olfactory dysfunction increased EtOH consumption in mice, which was accompanied by decreased LFP power and coherence in the reward system, which suggest that olfactory deficits changed activities in the reward system and could alter reward-seeking behaviors, which provide insights into the neurobiology of alcohol addiction.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105875"},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

(Poly)phenol-rich grape and blueberry extract prevents LPS-induced disruption of the blood-brain barrier through the modulation of the gut microbiota-derived uremic toxins (富含（多）酚的葡萄和蓝莓提取物通过调节肠道微生物群衍生的尿毒症毒素，防止 LPS 引起的血脑屏障破坏。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-09 DOI: 10.1016/j.neuint.2024.105878

Emily Connell , Gwénaëlle Le Gall , Simon McArthur , Leonie Lang , Bernadette Breeze , Matthew G. Pontifex , Saber Sami , Line Pourtau , David Gaudout , Michael Müller , David Vauzour

{"title":"(Poly)phenol-rich grape and blueberry extract prevents LPS-induced disruption of the blood-brain barrier through the modulation of the gut microbiota-derived uremic toxins","authors":"Emily Connell , Gwénaëlle Le Gall , Simon McArthur , Leonie Lang , Bernadette Breeze , Matthew G. Pontifex , Saber Sami , Line Pourtau , David Gaudout , Michael Müller , David Vauzour","doi":"10.1016/j.neuint.2024.105878","DOIUrl":"10.1016/j.neuint.2024.105878","url":null,"abstract":"<div><div>The dynamic protective capacity of (poly)phenols, attributed to their potent antioxidant and anti-inflammatory properties, has been consistently reported. Due to their capacity to alter gut microbiome composition, further actions of (poly)phenols may be exerted through the modulation of the microbiota-gut-brain axis. However, the underlying mechanisms remain poorly defined. Here, we investigated the protective effect of a (poly)phenol-rich grape and blueberry extract (Memophenol™), on the microbiota-gut-brain axis in a model of chronic low-grade inflammation (0.5 mg/kg/wk lipopolysaccharide (LPS) for 8 weeks). Dietary supplementation of male C57BL/6 J mice with Memophenol™ prevented LPS-induced increases in the microbe-derived uremia-associated molecules, indoxyl sulfate (IS) and trimethylamine <em>N</em>-oxide (TMAO). These changes coincided with shifts in gut microbiome composition, notably <em>Romboutsia</em> and <em>Desulfovibrio</em> abundance, respectively. In the brain, LPS exposure disrupted the marginal localisation of the endothelial tight junction ZO-1 and downregulated ZO-1 mRNA expression to an extent closely correlated with TMAO and IS levels; a process prevented by Memophenol™ intake. Hippocampal mRNA sequencing analysis revealed significant downregulation in regulatory pathways of neurodegeneration with Memophenol™ intake. These findings may indicate a novel protective role of the (poly)phenol-rich grape and blueberry extract on the endothelial tight junction component ZO-1, acting through modulation of gut microbial metabolism.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105878"},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Jun modulates endoplasmic reticulum stress-associated ferroptosis in dorsal root ganglia neurons during neuropathic pain by regulating Timp1 Jun通过调控Timp1调节神经病理性疼痛过程中背根神经节神经元中与内质网应激相关的铁突变。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2024-10-08 DOI: 10.1016/j.neuint.2024.105877

Ziqiang Lin , Yi Wang , Yingdong Deng , Lu Li , Yu Cao , Suo Wang , Xiangsheng Zhang , Guoda Ding , Jiurong Cheng , Simin Tang , Jun Zhou

{"title":"Jun modulates endoplasmic reticulum stress-associated ferroptosis in dorsal root ganglia neurons during neuropathic pain by regulating Timp1","authors":"Ziqiang Lin , Yi Wang , Yingdong Deng , Lu Li , Yu Cao , Suo Wang , Xiangsheng Zhang , Guoda Ding , Jiurong Cheng , Simin Tang , Jun Zhou","doi":"10.1016/j.neuint.2024.105877","DOIUrl":"10.1016/j.neuint.2024.105877","url":null,"abstract":"<div><div>Neuropathic pain (NP) is a complex disorder caused by lesions or diseases affecting the somatosensory nervous system, severely impacting patients' quality of life. Recent studies suggest ferroptosis may be involved in NP induction, but its precise mechanisms remain unclear. We used GO and KEGG pathway enrichment analyses to functionally annotate ferroptosis-related differentially expressed genes (FRDs). Through STRING and the maximum cluster centrality (MCC) algorithm, we identified five hub FRDs (Jun, Timp1, Egfr, Cdkn1a, Cdkn2a). Single-cell analysis revealed significant expression of Jun and Timp1 in neurons. Our study confirmed the association between ferroptosis and endoplasmic reticulum stress (ERS) in NP and validated changes in hub FRD expression across various NP animal models. In vitro experiments demonstrated that Jun regulates neuronal ferroptosis and ERS, particularly by modulating Timp1 expression. Transcription factor prediction and JASPAR binding site analysis elucidated the regulatory network involving Jun. ROC curve analysis of external datasets highlighted the diagnostic potential of hub FRDs and ERS-related differentially expressed genes (ERSRDs) in NP. Using the Comparative Toxicogenomics Database (CTD), we identified estradiol (E2) as a potential therapeutic drug targeting hub FRDs and ERSRDs. Molecular docking predicted its binding sites with Jun and Timp1, and in vivo experiments confirmed that E2 alleviated NP and reversed the expression of Jun and Timp1. This study underscores the crucial role of Jun and Timp1 in the interplay between ferroptosis and ERS, offering new insights and promising avenues for NP treatment.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105877"},"PeriodicalIF":4.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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