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Assessment of Expression of lncRNAs in Autistic Patients 自闭症患者体内 lncRNAs 的表达评估
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-08-26 DOI: 10.1007/s12031-024-02258-8
Saba Sane, Vera Ebrahimi, Zeinab Shirvani Farsani, Soudeh Ghafouri-Fard
{"title":"Assessment of Expression of lncRNAs in Autistic Patients","authors":"Saba Sane,&nbsp;Vera Ebrahimi,&nbsp;Zeinab Shirvani Farsani,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1007/s12031-024-02258-8","DOIUrl":"10.1007/s12031-024-02258-8","url":null,"abstract":"<div><p>Autism is a severe neurodevelopmental condition with unknown pathobiology. Nevertheless, multiple pieces of evidence suggest long non-coding RNA (lncRNA) dysregulation may be a contributing factor to this disorder. We investigated the association between the expression of five specific lncRNAs and autism. Peripheral blood was collected from 30 children with autism and 41 healthy children. The expression levels of <i>PCAT-29</i>, <i>lincRNA-ROR</i>, <i>LINC-PINT</i>, <i>lincRNA-p21</i>, and <i>PCAT-1</i> were calculated. Then, their significance as biomarkers was also evaluated. The expression of <i>LincRNA-ROR</i> (27 times), <i>LINC-PINT</i> (5.26 times), <i>LincRNA-p21</i> (4.54 times), <i>PCAT-29</i> (16.66 times), and <i>PCAT-1</i> (25 times) genes was significantly decreased in patients compared to the control group (<i>p</i> values &lt; 0.05). According to the ROC curve analysis for each lncRNA, <i>LincRNA-ROR</i>, <i>LINC-PINT</i>, <i>LincRNA-p21</i>, <i>PCAT-29</i>, and <i>PCAT-1</i> lncRNAs with diagnostic power of 0.85, 0.67, 0.64, 0.74, and 0.84, respectively, could be used as diagnostic biomarkers for autism. Additionally, significant positive correlations were reported between expression levels of <i>PCAT-1</i> and <i>PCAT-29</i> genes. Moreover, a positive correlation was detected between expression levels of <i>lincRNA-ROR</i> and patients’ age. The current study shows further pieces of evidence for deregulation of lncRNAs in autistic patients that show these lncRNAs may play an important part in the pathogenesis of ASD. However, the role of lncRNA in the neurobiology of autism needs to be investigated further.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054569","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
Associations Between Gut Microbiota and Alcohol Abuse: A Mendelian Randomisation and Bioinformatics Study 肠道微生物群与酗酒之间的关系:孟德尔随机化和生物信息学研究》。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-08-26 DOI: 10.1007/s12031-024-02259-7
Xu Wang, Lei Pan, Jingyan Gu, Lianping Gu, Meiqing Lou, Yaohua Liu
{"title":"Associations Between Gut Microbiota and Alcohol Abuse: A Mendelian Randomisation and Bioinformatics Study","authors":"Xu Wang,&nbsp;Lei Pan,&nbsp;Jingyan Gu,&nbsp;Lianping Gu,&nbsp;Meiqing Lou,&nbsp;Yaohua Liu","doi":"10.1007/s12031-024-02259-7","DOIUrl":"10.1007/s12031-024-02259-7","url":null,"abstract":"<div><p>Alcohol abuse, also known as Alcohol Use Disorder (AUD), is a substance dependency psychiatric disorder. We aimed to establish a causal relationship between specific gut microbiota and alcohol abuse using Mendelian Randomisation (MR) and bioinformatics methods. We acquired summary data of genome-wide association studies (GWAS) for gut microbiota and alcohol abuse from the Mibiogen and Finngen databases, respectively. We conducted MR analyses using various methodologies and mapped the single nucleotide polymorphisms (SNPs) to genes via the FUMA GWAS platform. We further performed multiple enrichment analyses and a Multi-variable Mendelian Randomisation (MVMR) approach to examine whether gut microbiota influences alcohol abuse by modulating neurotransmitter-related amino acids. The MR analysis revealed an inverse relationship between the genus <i>Eubacterium ventriosum group</i> and the <i>Porphyromonadaceae family</i> with alcohol abuse. Gene enrichment analysis showed that these genes are expressed in brain tissue and are involved in addictive disorders, psychiatric conditions, immunological processes, neurotransmitter synthesis and synaptic regulation. MVMR analysis suggested that the <i>Porphyromonadaceae family</i> as well as genus <i>Eubacterium ventriosum</i> group may suppress alcohol abuse through the metabolism of neurotransmitter-related amino acids, especially Tryptophan. The MR analysis and bioinformatics investigations indicate that the genus <i>Eubacterium ventriosum group</i> and <i>Porphyromonadaceae family</i> confer a protective effect against alcohol abuse, potentially through the modulation of synaptic function.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054570","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
Electroacupuncture Alleviates Streptozotocin-Induced Diabetic Neuropathic Pain via the TRPV1-Mediated CaMKII/CREB Pathway in Rats 电针通过 TRPV1 介导的 CaMKII/CREB 通路缓解大鼠链脲佐菌素诱发的糖尿病神经病理性疼痛
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-08-20 DOI: 10.1007/s12031-024-02256-w
Yinmu Zheng, Siyi Li, Yurong Kang, Qunqi Hu, Yu Zheng, Xiaoxiang Wang, Hengyu Chi, Keying Guo, Minjian Jiang, Zhouyuan Wei, Xiaomei Shao, Chi Xu, Boyu Liu, Junying Du, Xiaofen He, Jianqiao Fang, Zhenzhong Lu, Yongliang Jiang
{"title":"Electroacupuncture Alleviates Streptozotocin-Induced Diabetic Neuropathic Pain via the TRPV1-Mediated CaMKII/CREB Pathway in Rats","authors":"Yinmu Zheng,&nbsp;Siyi Li,&nbsp;Yurong Kang,&nbsp;Qunqi Hu,&nbsp;Yu Zheng,&nbsp;Xiaoxiang Wang,&nbsp;Hengyu Chi,&nbsp;Keying Guo,&nbsp;Minjian Jiang,&nbsp;Zhouyuan Wei,&nbsp;Xiaomei Shao,&nbsp;Chi Xu,&nbsp;Boyu Liu,&nbsp;Junying Du,&nbsp;Xiaofen He,&nbsp;Jianqiao Fang,&nbsp;Zhenzhong Lu,&nbsp;Yongliang Jiang","doi":"10.1007/s12031-024-02256-w","DOIUrl":"10.1007/s12031-024-02256-w","url":null,"abstract":"<div><p>Diabetic neuropathic pain (DNP) is a diabetic complication that causes severe pain and deeply impacts the quality of the sufferer’s daily life. Currently, contemporary clinical treatments for DNP generally exhibit a deficiency in effectiveness. Electroacupuncture (EA) is recognized as a highly effective and safe treatment for DNP with few side effects. Regrettably, the processes via which EA alleviates DNP are still poorly characterized. Transient receptor potential vanilloid 1 (TRPV1) and phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) are overexpressed on spinal cord dorsal horn (SCDH) in DNP rats, and co-localization is observed between them. Capsazepine, a TRPV1 antagonist, effectively reduced nociceptive hypersensitivity and downregulated the overexpression of phosphorylated CaMKIIα in rats with DNP. Conversely, the CaMKII inhibitor KN-93 did not have any impact on TRPV1. EA alleviated heightened sensitivity to pain caused by nociceptive stimuli and downregulated the level of TRPV1, p-CaMKIIα, and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) in DNP rats. Intrathecal injection of capsaicin, on the other hand, reversed the above effects of EA. These findings indicated that the CaMKII/CREB pathway on SCDH is located downstream of TRPV1 and is affected by TRPV1. EA alleviates DNP through the TRPV1-mediated CaMKII/CREB pathway.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003313","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
GDNF's Role in Mitigating Intestinal Reactive Gliosis and Inflammation to Improve Constipation and Depressive Behavior in Rats with Parkinson’s disease GDNF 在减轻肠道反应性胶质细胞增多和炎症以改善帕金森病大鼠便秘和抑郁行为中的作用
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-08-19 DOI: 10.1007/s12031-024-02254-y
Qin Xiaoling, Guo Yurong, Xue Ke, Qiu Yuxiang, An Panpan, Du Yinzhen, Li Xue, Liu Tingting, Tang Chuanxi
{"title":"GDNF's Role in Mitigating Intestinal Reactive Gliosis and Inflammation to Improve Constipation and Depressive Behavior in Rats with Parkinson’s disease","authors":"Qin Xiaoling,&nbsp;Guo Yurong,&nbsp;Xue Ke,&nbsp;Qiu Yuxiang,&nbsp;An Panpan,&nbsp;Du Yinzhen,&nbsp;Li Xue,&nbsp;Liu Tingting,&nbsp;Tang Chuanxi","doi":"10.1007/s12031-024-02254-y","DOIUrl":"10.1007/s12031-024-02254-y","url":null,"abstract":"<div><p>Constipation is a common symptom in patients with Parkinson's disease (PD) and is often associated with depression. Enteric glial cells (EGCs) are crucial for regulating intestinal inflammation and colon motility, and their activation can lead to the death of intestinal neurons. Glial cell line-derived neurotrophic factor (GDNF) has been recognized for its neuroprotective properties in various neurological disorders, including PD. This study explores the potential of GDNF in alleviating intestinal reactive gliosis and inflammation, thereby improving constipation and depressive behavior in a rat model of PD. A PD model was established via unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA). Five weeks post-injury, AAV5-GDNF (2 ~ 5 × 10<sup>^11</sup>) was intraperitoneally injected into experimental and control rats. Fecal moisture percentage (FMP) and colonic propulsion rate (CPPR) were used to evaluate colon motility. Colon-related inflammation and colonic epithelial morphology were assessed, and depressive behavior was analyzed one week before sampling. PD rats exhibited reduced colonic motility and GDNF expression, along with increased EGC reactivity and elevated levels of pro-inflammatory cytokines IL-1, IL-6, and TNF-α. Additionally, there was an up-regulation of CX43 and a decrease in PGP 9.5 expression. The intraperitoneal injection of AAV-GDNF significantly protected colonic neurons by inhibiting EGC activation and down-regulating CX43. This treatment also led to a notable reduction in depressive-like symptoms in PD rats with constipation. GDNF effectively reduces markers of reactive gliosis and inflammation, and promotes the survival of colonic neurons, and improves colonic motility in PD rats by regulating CX43 activity. Furthermore, GDNF treatment alleviates depressive behavior, suggesting that GDNF or its agonists could be promising therapeutic agents for managing gastrointestinal and neuropsychiatric symptoms associated with PD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999209","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
A Holistic Analysis of Alzheimer’s Disease-Associated lncRNA Communities Reveals Enhanced lncRNA-miRNA-RBP Regulatory Triad Formation Within Functionally Segregated Clusters 对阿尔茨海默病相关lncRNA群落的整体分析揭示了在功能分隔的群落中增强的lncRNA-miRNA-RBP调控三元组的形成。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-08-15 DOI: 10.1007/s12031-024-02244-0
Somenath Sen, Debashis Mukhopadhyay
{"title":"A Holistic Analysis of Alzheimer’s Disease-Associated lncRNA Communities Reveals Enhanced lncRNA-miRNA-RBP Regulatory Triad Formation Within Functionally Segregated Clusters","authors":"Somenath Sen,&nbsp;Debashis Mukhopadhyay","doi":"10.1007/s12031-024-02244-0","DOIUrl":"10.1007/s12031-024-02244-0","url":null,"abstract":"<p>Recent studies on the regulatory networks implicated in Alzheimer’s disease (AD) evince long non-coding RNAs (lncRNAs) as crucial regulatory players, albeit a poor understanding of the mechanism. Analyzing differential gene expression in the RNA-seq data from the post-mortem AD brain hippocampus, we categorized a list of AD-dysregulated lncRNA transcripts into functionally similar communities based on their <i>k-</i>mer profiles. Using machine-learning-based algorithms, their subcellular localizations were mapped. We further explored the functional relevance of each community through AD-dysregulated miRNA, RNA-binding protein (RBP) interactors, and pathway enrichment analyses. Further investigation of the miRNA–lncRNA and RBP–lncRNA networks from each community revealed the top RBPs, miRNAs, and lncRNAs for each cluster. The experimental validation community yielded ELAVL4 and miR-16-5p as the predominant RBP and miRNA, respectively. Five lncRNAs emerged as the top-ranking candidates from the RBP/miRNA-lncRNA networks. Further analyses of these networks revealed the presence of multiple regulatory triads where the RBP–lncRNA interactions could be augmented by the enhanced miRNA–lncRNA interactions. Our results advance the understanding of the mechanism of lncRNA-mediated AD regulation through their interacting partners and demonstrate how these functionally segregated but overlapping regulatory networks can modulate the disease holistically.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981430","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
Integrating Multi-omics to Identify Age-Related Macular Degeneration Subtypes and Biomarkers 整合多组学,识别老年性黄斑变性亚型和生物标记物。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-08-07 DOI: 10.1007/s12031-024-02249-9
Shenglai Zhang, Ying Yang, Jia Chen, Shu Su, Yu Cai, Xiaowei Yang, Aimin Sang
{"title":"Integrating Multi-omics to Identify Age-Related Macular Degeneration Subtypes and Biomarkers","authors":"Shenglai Zhang,&nbsp;Ying Yang,&nbsp;Jia Chen,&nbsp;Shu Su,&nbsp;Yu Cai,&nbsp;Xiaowei Yang,&nbsp;Aimin Sang","doi":"10.1007/s12031-024-02249-9","DOIUrl":"10.1007/s12031-024-02249-9","url":null,"abstract":"<div><p>Age-related macular degeneration (AMD) is one of the most common causes of irreversible vision loss in the elderly. Its pathogenesis is likely multifactorial, involving a complex interaction of metabolic and environmental factors, and remains poorly understood. Previous studies have shown that mitochondrial dysfunction and oxidative stress play a crucial role in the development of AMD. Oxidative damage to the retinal pigment epithelium (RPE) has been identified as one of the major mediators in the pathogenesis of age-related macular degeneration (AMD). Therefore, this article combines transcriptome sequencing (RNA-seq) and single-cell sequencing (scRNA-seq) data to explore the role of mitochondria-related genes (MRGs) in AMD. Firstly, differential expression analysis was performed on the raw RNA-seq data. The intersection of differentially expressed genes (DEGs) and MRGs was performed. This paper proposes a deep subspace nonnegative matrix factorization (DS-NMF) algorithm to perform a multi-layer nonlinear transformation on the intersection of gene expression profiles corresponding to AMD samples. The age of AMD patients is used as prior information at the network’s top level to change the data distribution. The classification is based on reconstructed data with altered distribution. The types obtained significantly differ in scores of multiple immune-related pathways and immune cell infiltration abundance. Secondly, an optimal AMD diagnosis model was constructed using multiple machine learning algorithms for external and qRT-PCR verification. Finally, ten potential therapeutic drugs for AMD were identified based on cMAP analysis. The AMD subtypes identified in this article and the diagnostic model constructed can provide a reference for treating AMD and discovering new drug targets.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896429","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
Drug Response of Iranian Alzheimer’s Patients to Rivastigmine Concerning Their Genotype for VDR rs11568820 and MTHFR C677T Variants: A Pharmacogenetic and Association Study 伊朗阿尔茨海默病患者对利伐斯的明的药物反应与其 VDR rs11568820 和 MTHFR C677T 变异基因型有关:药物遗传学与关联研究》。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-08-07 DOI: 10.1007/s12031-024-02253-z
Zahra Salimian Rizi, Leila Shams, Fatemeh Rezaei Rad, Mahdi Zamani
{"title":"Drug Response of Iranian Alzheimer’s Patients to Rivastigmine Concerning Their Genotype for VDR rs11568820 and MTHFR C677T Variants: A Pharmacogenetic and Association Study","authors":"Zahra Salimian Rizi,&nbsp;Leila Shams,&nbsp;Fatemeh Rezaei Rad,&nbsp;Mahdi Zamani","doi":"10.1007/s12031-024-02253-z","DOIUrl":"10.1007/s12031-024-02253-z","url":null,"abstract":"<div><p>Alzheimer’s disease is a neurodegenerative disorder with polygenic etiology. Genetic risk variants for Alzheimer’s disease differ among populations. Thus, discovering them in each population is clinically important. A total of 118 patients and 97 controls for VDR rs11568820 and 88 patients and 100 healthy controls for MTHFR C677T polymorphism were genotyped to evaluate the association of these polymorphisms with late-onset Alzheimer’s disease in the Iranian population, along with their impacts on the response to Rivastigmine treatment. The VDR C allele was significantly associated with Alzheimer’s disease and provided protection against it (<i>P</i> = 0.003, RR = 1.14, 95% CI 1.04–1.24), while the T allele increased susceptibility (<i>P</i> = 0.003, RR = 1.93, 95% CI 1.23–3.02). These results were also considerable upon excluding the effect of APOE ε4 allele. The Prevalence-corrected Positive Predictive Value was 1.71% for the VDR CC genotype and 4% for the VDR CT genotype, indicating lower and almost twofold higher chances of developing Alzheimer’s disease, respectively. No significant correlation was observed between MTHFR C677T and Alzheimer’s disease. Based on our pharmacogenetic study, MTHFR T allele carriers lacking APOE ε4 allele showed a better response to Rivastigmine treatment after a 2-year follow-up. Moreover, patients with VDR CC genotype displayed milder Alzheimer’s disease, particularly when coincided with the APOE ε4 allele. The VDR rs11568820 polymorphism affects both Alzheimer’s disease risk and the response to Rivastigmine in Iranian patients. Also, MTHFR C677T polymorphism may play a role in the response to Rivastigmine, through a pathway that needs to be elucidated in future studies.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900550","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
Inhibiting the JNK Signaling Pathway Attenuates Hypersensitivity and Anxiety-Like Behavior in a Rat Model of Non-specific Chronic Low Back Pain 抑制 JNK 信号通路可减轻非特异性慢性腰痛大鼠模型中的过度敏感和焦虑行为
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-07-24 DOI: 10.1007/s12031-024-02252-0
Yifan Li, Bingyu Zhang, Jie Xu, Xiao Jiang, Liang Jing, Yanghua Tian, Kai Wang, Juanjuan Zhang
{"title":"Inhibiting the JNK Signaling Pathway Attenuates Hypersensitivity and Anxiety-Like Behavior in a Rat Model of Non-specific Chronic Low Back Pain","authors":"Yifan Li,&nbsp;Bingyu Zhang,&nbsp;Jie Xu,&nbsp;Xiao Jiang,&nbsp;Liang Jing,&nbsp;Yanghua Tian,&nbsp;Kai Wang,&nbsp;Juanjuan Zhang","doi":"10.1007/s12031-024-02252-0","DOIUrl":"10.1007/s12031-024-02252-0","url":null,"abstract":"<div><p>Low back pain (LBP) has become a leading cause of disability worldwide. Astrocyte activation in the spinal cord plays an important role in the maintenance of latent sensitization of dorsal horn neurons in LBP. However, the role of spinal c-Jun N-terminal kinase (JNK) in astrocytes in modulating pain behavior of LBP model rats and its neurobiological mechanism have not been elucidated. Here, we investigate the role of the JNK signaling pathway on hypersensitivity and anxiety-like behavior caused by repetitive nerve growth factor (NGF) injections in male non-specific LBP model rats. LBP was produced by two injections (day 0, day 5) of NGF into multifidus muscle of the low backs of rats. We observed prolonged mechanical and thermal hypersensitivity in the low backs or hindpaws. Persistent anxiety-like behavior was observed, together with astrocyte, p-JNK, and neuronal activation and upregulated expression of monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL1) proteins in the spinal L2 segment. Second, the JNK inhibitor SP600125 was intrathecally administrated in rats from day 10 to day 12. It attenuated mechanical and thermal hypersensitivity of the low back or hindpaws and anxiety-like behavior. Meanwhile, SP600125 decreased astrocyte and neuronal activation and the expression of MCP-1 and CXCL1 proteins. These results showed that hypersensitivity and anxiety-like behavior induced by NGF in LBP rats could be attenuated by the JNK inhibitor, together with downregulation of spinal astrocyte activation, neuron activation, and inflammatory cytokines. Our results indicate that intervening with the spinal JNK signaling pathway presents an effective therapeutic approach to alleviating LBP.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750807","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
Prepubertal Repeated Berberine Supplementation Enhances Cerebrocerebellar Functions by Modulating Neurochemical and Behavioural Changes in Wistar Rats 青春期前反复补充小檗碱可通过调节Wistar大鼠的神经化学和行为变化增强其小脑功能
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-07-23 DOI: 10.1007/s12031-024-02250-2
Solomon Owumi, Joseph Chimezie, Moses Otunla, Bayode Oluwawibe, Harieme Agbarogi, Mayowa Anifowose, Uche Arunsi, Olatunde Owoeye
{"title":"Prepubertal Repeated Berberine Supplementation Enhances Cerebrocerebellar Functions by Modulating Neurochemical and Behavioural Changes in Wistar Rats","authors":"Solomon Owumi,&nbsp;Joseph Chimezie,&nbsp;Moses Otunla,&nbsp;Bayode Oluwawibe,&nbsp;Harieme Agbarogi,&nbsp;Mayowa Anifowose,&nbsp;Uche Arunsi,&nbsp;Olatunde Owoeye","doi":"10.1007/s12031-024-02250-2","DOIUrl":"10.1007/s12031-024-02250-2","url":null,"abstract":"<div><p>Antioxidant-rich supplementation plays an essential role in the function of mammals’ central nervous system. However, no research has documented the effect of berberine (BER) supplementation on the cerebrocerebellar function of prepubertal rats. The present study was designed to investigate the impact of BER supplementation on neurochemical and behavioural changes in prepubertal male rats. Five groups (90 ± 5 g, <i>n</i> = 7 each) of experimental rats were orally treated with corn oil or different doses of BER (25, 50, 100, and 200 mg/kg bw) from the 28th at 68 post-natal days. On the 69 days of life, animals underwent behavioural assessment in the open field, hanging wire, and negative geotaxis tests. The result revealed that BER administration improved locomotive and motor behaviour by increasing distance travelled, line crossings, average speed, time mobile, and absolute turn angle in open field test and decrease in time to re-orient on an incline plane, a decrease in immobility time relative to the untreated control. Furthermore, BER supplementation increased (<i>p</i> &lt; <i>0.05</i>) antioxidant enzyme activities such as SOD, CAT, GPx, GSH, and TSH and prevented increases (<i>p</i> &lt; <i>0.05</i>) in oxidative and inflammatory levels as indicated by decreases in RONS, LPO, XO, carbonyl protein, NO, MPO, and TNF-α compared to the untreated control. BER-treated animals a lessened number of dark-stained Nissl cells compared to the untreated control rats. Our findings revealed that BER minimised neuronal degeneration and lesions, improved animal behaviour, and suppressed oxidative and inflammatory mediators, which may probably occur through its agonistic effect on PPAR-α, PPAR-δ, and PPAR-γ – essential proteins known to resolve inflammation and modulate redox signalling towards antioxidant function.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747082","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
Acupuncture Therapy Modulating “Du” Channel Attenuates Ischemic Stroke-induced Disorders by Modulating REST-mediated miR-21/PDCD4 Signaling Transduction 通过调节REST介导的miR-21/PDCD4信号转导,针灸疗法调节 "杜 "字通道可减轻缺血性脑卒中引起的失调。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-07-20 DOI: 10.1007/s12031-024-02248-w
Gang Lei, Xiangbo Wu, Shuijie Zhang, Xiaoyun Tong, Gang Zhou
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