Journal of Molecular Neuroscience最新文献

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Investigating the Genetic Association of 40 Biochemical Indicators with Parkinson’s Disease 调查 40 个生化指标与帕金森病的遗传关联。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-10-04 DOI: 10.1007/s12031-024-02273-9
Zihao Wang, Huan Xia, Jianqiao Shi, Peidong Fan, Qiannan Cao, Yunfa Ding, Xinyu Du, Xinling Yang
{"title":"Investigating the Genetic Association of 40 Biochemical Indicators with Parkinson’s Disease","authors":"Zihao Wang,&nbsp;Huan Xia,&nbsp;Jianqiao Shi,&nbsp;Peidong Fan,&nbsp;Qiannan Cao,&nbsp;Yunfa Ding,&nbsp;Xinyu Du,&nbsp;Xinling Yang","doi":"10.1007/s12031-024-02273-9","DOIUrl":"10.1007/s12031-024-02273-9","url":null,"abstract":"<div><p>The mechanisms of Parkinson’s disease (PD) are not fully understood, which hinders the development of effective therapies. Research indicates that lower levels of biochemical indicators like bilirubin, vitamin D, and cholesterol may elevate the risk of PD. However, clinical studies on abnormal levels of biochemical indicators in PD patients’ circulation are inconsistent, leading to ongoing debate about their association with PD. Here, we investigate the genetic correlation between 40 biochemical indicators and PD using a bidirectional two-sample Mendelian randomization (MR) approach to uncover potential causal relationships. Data from genome-wide association studies (GWAS) were utilized, with genetic variations from specific lineages serving as instrumental variables (IVs). The methodology followed the STROBE-MR checklist and adhered to the three principal assumptions of MR. Statistical analyses employed methods including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Biochemical indicators including albumin, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) showed significant associations with PD risk. Elevated levels of albumin (OR = 1.246, 95% CI 1.006–1.542, <i>P</i> = 0.043) and SHBG (OR = 1.239, 95% CI 1.065–1.439, <i>P</i> = 0.005) were linked to higher PD risk. Conversely, increased CRP levels (OR = 0.663, 95% CI 0.517–0.851; <i>P</i> = 0.001) could potentially lower PD risk. The robustness of the results was confirmed through various MR analysis techniques, including assessments of directional pleiotropy and heterogeneity using MR-Egger intercept and MR-PRESSO methods. This study systematically reveals, for the first time at the genetic level, the relationship between 40 biochemical indicators and PD risk. Our research verifies the role of inflammation in PD and provides new genetic evidence, further advancing the understanding of PD pathogenesis. The study shows a positive correlation between albumin and SHBG with PD risk and a negative correlation between CRP and PD risk. This study identifies for the first time that SHBG may be involved in the onset of PD and potentially worsen disease progression.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370680","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
Genomic Validation in the UK Biobank Cohort Suggests a Role of C8B and MFG-E8 in the Pathogenesis of Trigeminal Neuralgia 英国生物库队列的基因组验证表明,C8B 和 MFG-E8 在三叉神经痛的发病机制中发挥作用。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-10-03 DOI: 10.1007/s12031-024-02263-x
Muataz S. Lafta, Gull Rukh, Sami Abu Hamdeh, Yasmina Molero, Aleksandr V. Sokolov, Elham Rostami, Helgi B. Schiöth
{"title":"Genomic Validation in the UK Biobank Cohort Suggests a Role of C8B and MFG-E8 in the Pathogenesis of Trigeminal Neuralgia","authors":"Muataz S. Lafta,&nbsp;Gull Rukh,&nbsp;Sami Abu Hamdeh,&nbsp;Yasmina Molero,&nbsp;Aleksandr V. Sokolov,&nbsp;Elham Rostami,&nbsp;Helgi B. Schiöth","doi":"10.1007/s12031-024-02263-x","DOIUrl":"10.1007/s12031-024-02263-x","url":null,"abstract":"<div><p>Trigeminal neuralgia (TN) is a severe facial pain disease of uncertain pathophysiology and unclear genetic background. Although recent research has reported a more important role of genetic factors in TN pathogenesis, few candidate genes have been proposed to date. The present study aimed to identify independent genetic variants in the protein-coding genes associated with TN. We focused on genes previously linked to TN based on the results of four proteomic studies conducted by our research team. The goal was to validate these findings on the genetic level to enhance our understanding of the role of genetics in TN. The study is based on the participants from UK Biobank cohort. Following quality control, 175 independent single nucleotide polymorphisms (SNPs) in 17 genes were selected. The study sample comprised of diagnosed TN cases (N = 555) and randomly matched controls (N = 6245) based on specific criteria. Two SNPs corresponding to <i>C8B</i> rs706484 [odds ratio (OR) (95% confidence interval (CI)): 1.357 (1.158–1.590); p: 0.00016] and <i>MFG-E8</i> rs2015495 [OR (95% CI): 1.313 (1.134–1.521); p: 0.00028] showed significant positive association with TN, indicating a positive effect of the SNP alleles on gene expression and disease risk. Interestingly, both SNPs are Expression Quantitative Trait Loci (eQTLs), and are associated with changes in the expression activity of their corresponding gene. Our findings suggest novel genetic associations between C8B, a key component of the complement system, and MFG-E8, which plays a role in regulating neuroinflammation, in relation to TN. The identified genetic variations may help explain why some individuals develop TN while others do not, indicating a potential genetic predisposition to the condition.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363931","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 Role of Thioredoxin System in Shank3 Mouse Model of Autism 硫氧还蛋白系统在 Shank3 自闭症小鼠模型中的作用
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-30 DOI: 10.1007/s12031-024-02270-y
Wisam Bazbaz, Maryam Kartawy, Wajeha Hamoudi, Shashank Kumar Ojha, Igor Khaliulin, Haitham Amal
{"title":"The Role of Thioredoxin System in Shank3 Mouse Model of Autism","authors":"Wisam Bazbaz,&nbsp;Maryam Kartawy,&nbsp;Wajeha Hamoudi,&nbsp;Shashank Kumar Ojha,&nbsp;Igor Khaliulin,&nbsp;Haitham Amal","doi":"10.1007/s12031-024-02270-y","DOIUrl":"10.1007/s12031-024-02270-y","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive behaviors, and restricted interests. Unfortunately, the underlying molecular mechanism behind ASD remains unknown. It has been reported that oxidative and nitrosative stress are strongly linked to ASD. We have recently found that nitric oxide (NO•) and its products play an important role in this disorder. One of the key proteins associated with NO• is thioredoxin (Trx). We hypothesize that the Trx system is altered in the <i>Shank3</i> KO mouse model of autism, which may lead to a decreased activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in oxidative stress, and thus, contributing to ASD-related phenotypes. To test this hypothesis, we conducted in vivo behavioral studies and used primary cortical neurons derived from the <i>Shank3</i> KO mice and human SH-SY5Y cells with <i>SHANK3</i> mutation. We showed significant changes in the levels and activity of Trx redox proteins in the <i>Shank3</i> KO mice. A Trx1 inhibitor PX-12 decreased Trx1 and Nrf2 expression in wild-type mice, causing abnormal alterations in the levels of synaptic proteins and neurotransmission markers, and an elevation of nitrosative stress. Trx inhibition resulted in an ASD-like behavioral phenotype, similar to that of <i>Shank3</i> KO mice. Taken together, our findings confirm the strong link between the Trx system and ASD pathology, including the increased oxidative/nitrosative stress, and synaptic and behavioral deficits. The results of this study may pave the way for identifying novel drug targets for ASD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338947","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
An early Transcriptomic Investigation in Adult Patients with Spinal Muscular Atrophy Under Treatment with Nusinersen 对接受 Nusinersen 治疗的成年脊髓性肌肉萎缩症患者进行早期转录组学研究。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-26 DOI: 10.1007/s12031-024-02251-1
Maria Liguori, Annalisa Bianco, Alessandro Introna, Arianna Consiglio, Giammarco Milella, Elena Abbatangelo, Eustachio D’Errico, Flavio Licciulli, Giorgio Grillo, Isabella Laura Simone
{"title":"An early Transcriptomic Investigation in Adult Patients with Spinal Muscular Atrophy Under Treatment with Nusinersen","authors":"Maria Liguori,&nbsp;Annalisa Bianco,&nbsp;Alessandro Introna,&nbsp;Arianna Consiglio,&nbsp;Giammarco Milella,&nbsp;Elena Abbatangelo,&nbsp;Eustachio D’Errico,&nbsp;Flavio Licciulli,&nbsp;Giorgio Grillo,&nbsp;Isabella Laura Simone","doi":"10.1007/s12031-024-02251-1","DOIUrl":"10.1007/s12031-024-02251-1","url":null,"abstract":"<div><p>Spinal muscular atrophy (SMA) is a rare degenerative disorder with loss of motor neurons caused by mutations in the <i>SMN1</i> gene. Nusinersen, an antisense oligonucleotide, was approved for SMA treatment to compensate the deficit of the encoded protein SMN by modulating the pre–mRNA splicing of <i>SMN2</i>, the centromeric homologous of <i>SMN1</i>, thus inducing the production of a greater amount of biologically active protein. Here, we reported a 10-month transcriptomics investigation in 10 adult SMA who received nusinersen to search for early genetic markers for clinical monitoring. By comparing their profiles with age-matched healthy controls (HC), we also analyzed the changes in miRNA/mRNAs expression and miRNA-target gene interactions possibly associated with SMA. A multidisciplinary approach of HT-NGS followed by bioinformatics/biostatistics analysis was applied. Within the study interval, those SMA patients who showed some clinical improvements were characterized by having the <i>SMN2/SMN1</i> ratio slightly increased over the time, while in the stable ones the ratio decreased, suggesting that the estimation of <i>SMN2/SMN1</i> expression may be an early indicator of nusinersen efficacy<b>.</b> On the other hand, the expression of 38/147 genes/genetic regions DE at T0 between SMA and HC like <i>TRADD</i> and <i>JUND</i> resulted “restored” at T10. We also confirmed the dysregulation of miR-146a(-5p), miR-324-5p and miR-423-5p in SMA subjects. Of interest, miR-146a-5p targeted <i>SMN1</i>, in line with experimental evidence showing the key role of astrocyte-produced miR-146a in SMA motor neuron loss. Molecular pathways such as NOTCH, NF-kappa B, and Toll-like receptor signalings seem to be involved in the SMA pathogenesis. </p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338946","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
Lactoferrin Protects Against Rotenone-Induced Toxicity in Dopaminergic SH-SY5Y Cells through the Modulation of Apoptotic-Associated Pathways 乳铁蛋白通过调节凋亡相关途径保护多巴胺能SH-SY5Y细胞免受罗替酮诱导的毒性影响
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-19 DOI: 10.1007/s12031-024-02267-7
Shin Jie Yong, Abhi Veerakumarasivam, Seong Lin Teoh, Wei Ling Lim, Jactty Chew
{"title":"Lactoferrin Protects Against Rotenone-Induced Toxicity in Dopaminergic SH-SY5Y Cells through the Modulation of Apoptotic-Associated Pathways","authors":"Shin Jie Yong,&nbsp;Abhi Veerakumarasivam,&nbsp;Seong Lin Teoh,&nbsp;Wei Ling Lim,&nbsp;Jactty Chew","doi":"10.1007/s12031-024-02267-7","DOIUrl":"10.1007/s12031-024-02267-7","url":null,"abstract":"<p>Parkinson’s disease (PD) is a common motor neurodegenerative disease that still lacks effective therapeutic options. Previous studies have reported that lactoferrin exhibited neuroprotective effects in cellular and animal models of PD, typically induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>) synthetic toxin. However, the neuroprotective capacity of lactoferrin in the rotenone-induced cellular model of PD remains relatively less established. Unlike MPTP/MPP<sup>+</sup>, rotenone is a naturally occurring environmental toxin known to induce chronic toxicity and increase the risk of PD in humans. In this study, we constructed a cellular model of PD by differentiating SH-SY5Y neuroblastoma cells with retinoic acid into mature dopaminergic neurons with increased β-tubulin III and tyrosine hydroxylase expression, followed by 24 h of rotenone exposure. Using this cellular model of PD, we showed that lactoferrin (1–10 µg/ml) pre-treatment for 48 h decreased loss of cell viability, mitochondrial membrane potential impairment, reactive oxygen species generation and pro-apoptotic activities (pan-caspase activation and nuclear condensation) in cells exposed to rotenone (1 and 5 µM) using biochemical assays, Hoechst 33342 staining and immunocytochemical techniques. We further demonstrated that 48 h of lactoferrin (10 µg/ml) pre-treatment decreased Bax:Bcl2 ratio and p42/44 mitogen-activated protein kinase expression but increased pAkt expression in 5 µM rotenone-exposed cells. Our study demonstrates that lactoferrin neuroprotective capacity is present in the rotenone-induced cellular model of PD, further supporting lactoferrin as a potential PD therapeutic that warrants further studies.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249638","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
Involvement of CXCL10 rs4256246, CXCR4 rs2228014, CCR2 rs1799864 and CXCL16 rs2277680 in the Predisposition to Schizophrenia CXCL10 rs4256246、CXCR4 rs2228014、CCR2 rs1799864 和 CXCL16 rs2277680 与精神分裂症易感性的关系
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-12 DOI: 10.1007/s12031-024-02257-9
Hana Saoud, Hajer Foddha, Youssef Aflouk, Besma Bel Hadj Jrad
{"title":"Involvement of CXCL10 rs4256246, CXCR4 rs2228014, CCR2 rs1799864 and CXCL16 rs2277680 in the Predisposition to Schizophrenia","authors":"Hana Saoud,&nbsp;Hajer Foddha,&nbsp;Youssef Aflouk,&nbsp;Besma Bel Hadj Jrad","doi":"10.1007/s12031-024-02257-9","DOIUrl":"10.1007/s12031-024-02257-9","url":null,"abstract":"<div><p>Chemokine ligands and their receptors have acquired less attention than pro- and anti-inflammatory cytokines in schizophrenia (SCZ). Thus, we aimed to examine the impact of functional polymorphisms of the chemokine genes CXCL10, CXCL16, CXCR4, and CCR2 in the development of SCZ. Using PCR–RFLP, we analyzed the selected polymorphisms in a Tunisian cohort composed of 200 patients with SCZ and 200 healthy controls. Our preliminary data suggest that the minor allele A of CXCL10 rs4256246 is significantly associated with likelihood of SCZ (<i>P</i><sub>Adjusted</sub> = 0.00002) and more precisely to paranoid patients with late-onset SCZ (<i>P</i><sub>Adjusted</sub> = 0.0007). However, the mutated allele T of CXCR4 rs2228014 showed a significant protective impact against SCZ (<i>P</i><sub>Adjusted</sub> = 0.000007) and especially to male sex (<i>P</i><sub>Adjusted</sub> = 0.000003). This effect persists among the undifferentiated patients with early-onset SCZ (<i>P</i><sub>Adjusted</sub> = 0.002). Following the stratified analyses, CCR2 rs1799864 and CXCL16 rs2277680 were significantly correlated with the clinical symptoms among disorganized patients. As regards haplotype analysis, we noted that G<b>AT</b>G haplotype was associated with protection against SCZ (<i>P</i><sub>Adjusted</sub> = 0.0087) but the<b> A</b>GCG haplotype was correlated with susceptibility to this disease (<i>P</i><sub>Adjusted</sub> = 0.014). Our preliminary results suggested that CXCL10 rs4256246 enhanced susceptibility to SCZ, while CXCR4 rs2228014 seemed to be protective factor. Furthermore, we identified a substantial correlation between CCR2 rs1799864 and CXCL16 rs2277680 with the clinical signs of the disorder. To validate these results and clarify the functional significance of the targeted polymorphisms in SCZ, more independent research is needed.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211527","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
Identification and Validation of Endoplasmic Reticulum Stress-Related Gene in Traumatic Brain Injury 创伤性脑损伤中内质网应激相关基因的鉴定与验证
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-12 DOI: 10.1007/s12031-024-02265-9
Gengshui Zhao, Yongqi Fu, Chao Yang, Xuehui Yang, Xiaoxiao Hu
{"title":"Identification and Validation of Endoplasmic Reticulum Stress-Related Gene in Traumatic Brain Injury","authors":"Gengshui Zhao,&nbsp;Yongqi Fu,&nbsp;Chao Yang,&nbsp;Xuehui Yang,&nbsp;Xiaoxiao Hu","doi":"10.1007/s12031-024-02265-9","DOIUrl":"10.1007/s12031-024-02265-9","url":null,"abstract":"<div><p>Endoplasmic reticulum stress (ERS) plays an essential role in the development of traumatic brain injury (TBI). We aimed to identify and validate the potential ERS-related genes of TBI through bioinformatics analysis and in vitro cell experiment. A total of 19 TBI and ERS-related genes were obtained from the GeneCards database and Comparative Toxicogenomics Database (CTD). Enrichment analysis primarily enriched in apoptosis. NFE2L2 was identified as a hub gene based on the protein–protein interactions (PPI) network that combined seven ranked methods included in cytoHubba. To further explore the effect of Nrf2, the protein encoded by NFE2L2, on ERS-induced apoptosis, we conducted cell experiments with tert-butylhydroquinone (tBHQ), the classical inducer of Nrf2. Western blot suggested tBHQ pretreatment could diminish ERS and reduce the protein expressions of apoptosis in the primary cultured neuron injury model. These data may establish some theoretical basis for the treatment of TBI and provide inspiration and innovative ideas for clinicians and pathologists to understand TBI comprehensively.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211528","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
Association of Estrogen Receptor-α and Aryl Hydrocarbon Receptor Gene Polymorphisms with Ischemic Stroke in an Egyptian Population: A Pilot Study 埃及人群中雌激素受体-α和芳香烃受体基因多态性与缺血性中风的关系:一项试点研究
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-12 DOI: 10.1007/s12031-024-02255-x
Sara A. Aboelroos, Dina Gamal El Segaey, Amr Kamal Abd Elgawad, Marwa Orabi, Marwa Hussein Mohamed, Nashwa R. Hassan
{"title":"Association of Estrogen Receptor-α and Aryl Hydrocarbon Receptor Gene Polymorphisms with Ischemic Stroke in an Egyptian Population: A Pilot Study","authors":"Sara A. Aboelroos,&nbsp;Dina Gamal El Segaey,&nbsp;Amr Kamal Abd Elgawad,&nbsp;Marwa Orabi,&nbsp;Marwa Hussein Mohamed,&nbsp;Nashwa R. Hassan","doi":"10.1007/s12031-024-02255-x","DOIUrl":"10.1007/s12031-024-02255-x","url":null,"abstract":"<div><p>Stroke is the second leading cause of death and a major contributor to disability worldwide, with the highest prevalence in developing countries. Ischemic stroke (IS) is a complex disease resulting from genetic and environmental interactions. The present work is a pilot study exploring the association of estrogen receptor-α (<i>ESR1</i>) and aryl hydrocarbon receptor (<i>AHR</i>) SNPs with IS in a small Egyptian population of IS patients. Sixty IS patients and 60 matched healthy controls were included in this case–control study. Genotyping of <i>ESR1</i> PvuII (rs2234693), <i>ESR1</i> XbaI (rs9340799), and <i>AHR</i> rs2066853 SNPs was performed using real-time PCR. <i>ESR1</i> PvuII TC and CC genotypes were associated with IS (odds ratio (OR) = 2.821, 95% confidence interval (CI) = 1.204–6.609, <i>p</i> = 0.017, and OR = 9.455, 95% CI = 2.222–40.237, <i>p</i> = 0.002, respectively), and TC genotype in female IS (OR = 4.018, 95% CI = 1.117–14.455, <i>p</i> = 0.033). Additionally, <i>ESR1</i> XbaI GA and GG genotypes were associated with IS (OR = 2.833, 95% CI = 1.190–6.749, <i>p</i> = 0.019, and OR = 34.000, 95% CI = 6.965–165.980, <i>p</i> &lt; 0.001, respectively), and the AG and GG genotypes in male IS (OR = 3.378, 95% CI = 1.103–10.347, <i>p</i> = 0.033 and OR = 22.8, 95% CI = 2.580–201.488, <i>p</i> = 0.005, respectively) and the GG genotype in female IS (95% CI = 7.259–1115.914, <i>p</i> &lt; 0.001). <i>ESR1</i> PvuII and XbaI haplotypes C—A, T—G, and C—A increased the risk of IS in both genders, in male IS, and in female IS apart from C—A. The AG genotype of <i>AHR</i> rs2066853 was associated with male IS (OR = 6.900, 95% CI = 2.120–22.457 <i>p</i> = 0.001). <i>ESR1</i> PvuII, <i>ESR1</i> XbaI, and <i>AHR</i> rs2066853 SNPs are associated with IS in Egyptians. However, this is a small sample, and the findings should be replicated in a larger population.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211526","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
Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity ADNP/NAP(达武内酯)对可卡因诱导的可塑性的性别特异性调控
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-10 DOI: 10.1007/s12031-024-02234-2
Yael Toren, Yarden Ziv, Shlomo Sragovich, R. Anne McKinney, Segev Barak, Shula Shazman, Illana Gozes
{"title":"Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity","authors":"Yael Toren,&nbsp;Yarden Ziv,&nbsp;Shlomo Sragovich,&nbsp;R. Anne McKinney,&nbsp;Segev Barak,&nbsp;Shula Shazman,&nbsp;Illana Gozes","doi":"10.1007/s12031-024-02234-2","DOIUrl":"10.1007/s12031-024-02234-2","url":null,"abstract":"<div><p>Cocaine use disorder (CUD) is a chronic neuropsychiatric disorder estimated to effect 1–3% of the population. Activity-dependent neuroprotective protein (ADNP) is essential for brain development and functioning, shown to be protective in fetal alcohol syndrome and to regulate alcohol consumption in adult mice. The goal of this study was to characterize the role of ADNP, and its active peptide NAP (NAPVSIPQ), which is also known as davunetide (investigational drug) in mediating cocaine-induced neuroadaptations. Real time PCR was used to test levels of <i>Adnp</i> and <i>Adnp2</i> in the nucleus accumbens (NAc), ventral tegmental area (VTA), and dorsal hippocampus (DH) of cocaine-treated mice (15 mg/kg). Adnp heterozygous <i>(Adnp</i> <sup>+/−</sup>)and wild-type <i>(Adnp</i> <sup>+/−</sup>) mice were further tagged with excitatory neuronal membrane-expressing green fluorescent protein (GFP) that allowed for <i>in vivo</i> synaptic quantification. The mice were treated with cocaine (5 injections; 15 mg/kg once every other day) with or without NAP daily injections (0.4 µg/0.1 ml) and sacrificed following the last treatment. We analyzed hippocampal CA1 pyramidal cells from 3D confocal images using the Imaris x64.8.1.2 (Oxford Instruments) software to measure changes in dendritic spine density and morphology. <i>In silico</i> ADNP/NAP/cocaine structural modeling was performed as before. Cocaine decreased <i>Adnp</i> and <i>Adnp2</i> expression 2 h after injection in the NAc and VTA of male mice, with mRNA levels returning to baseline levels after 24 h. Cocaine further reduced hippocampal spine density, particularly synaptically weaker immature thin and stubby spines, in male <i>Adnp</i><sup>+/+</sup>) mice while increasing synaptically stronger mature (mushroom) spines in <i>Adnp</i><sup>+/−</sup>) male mice and thin and stubby spines in females. Lastly, we showed that cocaine interacts with ADNP on a zinc finger domain identical to ketamine and adjacent to a NAP-zinc finger interaction site. Our results implicate ADNP in cocaine abuse, further placing the ADNP gene as a key regulator in neuropsychiatric disorders. Ketamine/cocaine and NAP treatment may be interchangeable to some degree, implicating an interaction with adjacent zinc finger motifs on ADNP and suggestive of a potential sex-dependent, non-addictive NAP treatment for CUD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02234-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211548","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
REV-ERBα Mitigates Astrocyte Activation and Protects Dopaminergic Neurons from Damage REV-ERBα 可减轻星形胶质细胞的激活并保护多巴胺能神经元免受损伤
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-09-10 DOI: 10.1007/s12031-024-02264-w
Xiaoyu Wang, Hui Zhi, Zongqin Zhang, Jingwei Li, Dongkai Guo
{"title":"REV-ERBα Mitigates Astrocyte Activation and Protects Dopaminergic Neurons from Damage","authors":"Xiaoyu Wang,&nbsp;Hui Zhi,&nbsp;Zongqin Zhang,&nbsp;Jingwei Li,&nbsp;Dongkai Guo","doi":"10.1007/s12031-024-02264-w","DOIUrl":"10.1007/s12031-024-02264-w","url":null,"abstract":"<p>Parkinson’s disease (PD) is characterized by astrocyte activation and disruptions in circadian rhythm. Within the astrocyte population, two distinct reactive states exist: A1 and A2. A1 astrocytes are associated with neurotoxicity and inflammation, while A2 astrocytes exhibit neuroprotective functions. Our investigation focused on the role of REV-ERBα, a member of the nuclear receptor superfamily and a key regulator of the circadian clock, in astrocyte activation. We observed that REV-ERBα expression in A1 astrocytes was reduced to one-third of its normal level. Notably, activation of REV-ERBα prompted a transformation of astrocytes from A1 to A2. Mechanistically, REV-ERBα inhibition was linked to the classical NF-κB pathway, while it concurrently suppressed the STAT3 pathway. Furthermore, astrocytes with low REV-ERBα expression were associated with dopaminergic neurons apoptosis. Intriguingly, the opposite effect was observed when using a REV-ERBα agonist, which mitigated astrocyte activation and reduced dopaminergic neuron damage by 50%. In summary, our study elucidates the pivotal role of REV-ERBα in modulating astrocyte function and its potential implications in PD pathogenesis.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211545","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
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