Journal of Molecular Neuroscience最新文献

{"title":"Aneuploidy is Linked to Neurological Phenotypes Through Oxidative Stress","authors":"Anowarul Islam,&nbsp;Zeeshan Shaukat,&nbsp;Rashid Hussain,&nbsp;Michael G. Ricos,&nbsp;Leanne M. Dibbens,&nbsp;Stephen L. Gregory","doi":"10.1007/s12031-024-02227-1","DOIUrl":"10.1007/s12031-024-02227-1","url":null,"abstract":"<div><p>Aneuploidy, having an aberrant genome, is gaining increasing attention in neurodegenerative diseases. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift which makes these cells sensitive to internal and environmental stresses. A growing body of research from numerous laboratories suggests that many neurodegenerative disorders, especially Alzheimer’s disease and frontotemporal dementia, are characterised by neuronal aneuploidy and the ensuing apoptosis, which may contribute to neuronal loss. Using <i>Drosophila</i> as a model, we investigated the effect of induced aneuploidy in GABAergic neurons. We found an increased proportion of aneuploidy due to <i>Mad2</i> depletion in the third-instar larval brain and increased cell death. Depletion of <i>Mad2</i> in GABAergic neurons also gave a defective climbing and seizure phenotype. Feeding animals an antioxidant rescued the climbing and seizure phenotype. These findings suggest that increased aneuploidy leads to higher oxidative stress in GABAergic neurons which causes cell death, climbing defects, and seizure phenotype. Antioxidant feeding represents a potential therapy to reduce the aneuploidy-driven neurological phenotype.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02227-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829411","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}

{"title":"Behavioral and Metabolic Effects of ABCG4 KO in the APPswe,Ind (J9) Mouse Model of Alzheimer’s Disease","authors":"Vincent Fong,&nbsp;Babunageswararao Kanuri,&nbsp;Owen Traubert,&nbsp;Min Lui,&nbsp;Shailendra B. Patel","doi":"10.1007/s12031-024-02214-6","DOIUrl":"10.1007/s12031-024-02214-6","url":null,"abstract":"<div><p>The pathogenesis of Alzheimer’s disease (AD) is complex and involves an imbalance between production and clearance of amyloid-ß peptides (Aß), resulting in accumulation of Aß in senile plaques. Hypercholesterolemia is a major risk factor for developing AD, with cholesterol shown to accumulate in senile plaques and increase production of Aß. ABCG4 is a member of the ATP-binding cassette transporters predominantly expressed in the CNS and has been suggested to play a role in cholesterol and Aß efflux from the brain. In this study, we bred <i>Abcg4</i> knockout (KO) with the APP^Swe,Ind (J9) mouse model of AD to test the hypothesis that loss of <i>Abcg4</i> would exacerbate the AD phenotype. Unexpectedly, no differences were observed in novel object recognition (NOR) and novel object placement (NOP) behavioral tests, or on histologic examinations of brain tissues for senile plaque numbers. Furthermore, clearance of radiolabeled Aß from the brains did not differ between <i>Abcg4</i> KO and control mice. Metabolic testing by indirect calorimetry, glucose tolerance test (GTT), and insulin tolerance test (ITT) were also mostly similar between groups with only a few mild metabolic differences noted. Overall, these data suggest that the loss of ABCG4 did not exacerbate the AD phenotype.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02214-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652710","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}

{"title":"A Prognostic Methylation-Driven Two-Gene Signature in Medulloblastoma","authors":"Gustavo Lovatto Michaelsen,&nbsp;Lívia dos Reis Edinger da Silva,&nbsp;Douglas Silva de Lima,&nbsp;Mariane da Cunha Jaeger,&nbsp;André Tesainer Brunetto,&nbsp;Rodrigo Juliani Siqueira Dalmolin,&nbsp;Marialva Sinigaglia","doi":"10.1007/s12031-024-02203-9","DOIUrl":"10.1007/s12031-024-02203-9","url":null,"abstract":"<div><p>Medulloblastoma (MB) is one of the most common pediatric brain tumors and it is estimated that one-third of patients will not achieve long-term survival. Conventional prognostic parameters have limited and unreliable correlations with MB outcome, presenting a major challenge for patients’ clinical improvement. Acknowledging this issue, our aim was to build a gene signature and evaluate its potential as a new prognostic model for patients with the disease. In this study, we used six datasets totaling 1679 samples including RNA gene expression and DNA methylation data from primary MB as well as control samples from healthy cerebellum. We identified methylation-driven genes (MDGs) in MB, genes whose expression is correlated with their methylation. We employed LASSO regression, incorporating the MDGs as a parameter to develop the prognostic model. Through this approach, we derived a two-gene signature (GS-2) of candidate prognostic biomarkers for MB (<i>CEMIP</i> and <i>NCBP3</i>). Using a risk score model, we confirmed the GS-2 impact on overall survival (OS) with Kaplan-Meier analysis. We evaluated its robustness and accuracy with receiver operating characteristic curves predicting OS at 1, 3, and 5 years in multiple independent datasets. The GS-2 showed highly significant results as an independent prognostic biomarker compared to traditional MB markers. The methylation-regulated GS-2 risk score model can effectively classify patients with MB into high and low-risk, reinforcing the importance of this epigenetic modification in the disease. Such genes stand out as promising prognostic biomarkers with potential application for MB treatment.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653924","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}

{"title":"Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms","authors":"Xi-Lin Yang,&nbsp;Zheng Zeng,&nbsp;Chen Wang,&nbsp;Yun-Long Sheng,&nbsp;Guang-Yu Wang,&nbsp;Fu-Quan Zhang,&nbsp;Xin Lian","doi":"10.1007/s12031-024-02218-2","DOIUrl":"10.1007/s12031-024-02218-2","url":null,"abstract":"<div><p>We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS&lt;1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (<i>P</i>&lt;0.05) and greater infiltration of immune suppression cells compared to LTS (<i>P</i>&lt;0.05). Four genes, namely, <i>OSMR</i>, <i>FMOD</i>, <i>CXCL14</i>, and <i>TIMP1</i>, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (<i>C</i>-index, 0.791; 0.772–0.817) and validation cohort (<i>C</i>-index, 0.770; 0.751–0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656977","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}

{"title":"Expression Patterns of miRNAs in Egyptian Children with ADHD: Clinical Study with Correlation Analysis","authors":"Hala M. Zeidan,&nbsp;Neveen Hassan Nashaat,&nbsp;Maha Hemimi,&nbsp;Adel F. Hashish,&nbsp;Amal Elsaeid,&nbsp;Nagwa Abd EL-Ghaffar,&nbsp;Suzette I. Helal,&nbsp;Nagwa A. Meguid","doi":"10.1007/s12031-024-02220-8","DOIUrl":"10.1007/s12031-024-02220-8","url":null,"abstract":"<div><p>ADHD has huge knowledge gaps concerning its etiology. MicroRNAs (miRNAs) provide promising diagnostic biomarkers of human pathophysiology and may be a novel therapeutic option. The aim was to investigate the levels of miR-34c-3p, miR-155, miR-138-1, miR-296-5p, and plasma brain-derived neurotrophic factor (BDNF) in a group of children with ADHD compared to neurotypicals and to explore correlations between these measures and some clinical data. The participants were children with ADHD in Group I (<i>N</i> = 41; age: 8.2 ± 2) and neurotypical ones in Group II (<i>N</i> = 40; age: 8.6 ± 2.5). Group I was subjected to clinical examination, the Stanford Binet intelligence scale-5, the preschool language scale, and Conner’s parent rating scale-R. Measuring the expression levels of the miRNAs was performed by <i>qRT-PCR</i> for all participants. The BDNF level was measured by ELISA. The lowest scores on the IQ subtest were knowledge and working memory. No discrepancies were noticed between the receptive and expressive language ages. The highest scores on the Conner’s scale were those for cognitive problems. Participants with ADHD exhibited higher plasma BDNF levels compared to controls (<i>p</i> = 0.0003). Expression patterns of only miR-34c-3p and miR-138-1 were downregulated with significant statistical differences (p˂0.01). However, expression levels of miR-296-5p showed negative correlation with the total scores of IQ (<i>p</i> = 0.03). MiR-34c-3p, miR-138-1, while BDNF showed good diagnostic potential. The downregulated levels of miR-34c-3p and miR-138-1, together with high BDNF levels, are suggested to be involved in the etiology of ADHD in Egyptian children. Gender differences influenced the expression patterns of miRNAs only in children with ADHD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02220-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140669019","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}

{"title":"Genetic and Phenotypic Profiling of Triptan Users in a Swedish Cluster Headache Cohort","authors":"Felicia Jennysdotter Olofsgård,&nbsp;Caroline Ran,&nbsp;Yuyan Qin,&nbsp;Carmen Fourier,&nbsp;Elisabet Waldenlind,&nbsp;Anna Steinberg,&nbsp;Christina Sjöstrand,&nbsp;Andrea Carmine Belin","doi":"10.1007/s12031-024-02219-1","DOIUrl":"10.1007/s12031-024-02219-1","url":null,"abstract":"<div><p>Up to 25% of individuals who live with cluster headache (CH), an extremely painful primary headache disorder, do not adequately respond to the first-line treatment, triptans. Studies have indicated that genetic variants can play a role in treatment response. Likewise, differences in clinical characteristics can give clues to mechanisms underlying triptan non-response. Our aim was to investigate five genetic variants previously implicated in triptan response and their relation to triptan usage in our Swedish CH cohort and to investigate potential distinctions in clinical characteristics. 545 CH patients were screened for the genetic variants rs1024905, rs6724624, rs4795541, rs5443, and rs2651899 with a case control design based on triptan usage. Analysis of clinical characteristics was based on self-reported questionnaire data from 893 patients. One genetic variant, rs1024905, was significantly associated with triptan non-usage in CH (<i>Pc</i> = 0.010). In addition, multi-allele effector analysis showed that individuals with a higher number of effector variants were less likely to use triptans (<i>P</i> = 0.007). Analysis of clinical characteristics showed that triptan users were more likely to have alcohol as a trigger (57.4% vs 43.4%, <i>P</i> = 0.002), have autonomic symptoms (95.1% vs 88.1%, <i>P</i> = 0.002), and be current smokers (27.0% vs 21.9%, <i>P</i> = 0.033) compared to non-users. These results support the hypothesis that genetic variants can play a role in triptan usage in CH and that patients with a typical CH phenotype are more likely to use triptans.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02219-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615410","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}

{"title":"Neuroprotective Effect of Sterculia setigera Leaves Hydroethanolic\u0000 Extract","authors":"Yendubé T. Kantati,&nbsp;Magloire K. Kodjo,&nbsp;Benjamin Lefranc,&nbsp;Magali Basille-Dugay,&nbsp;Sébastien Hupin,&nbsp;Isabelle Schmitz,&nbsp;Jérôme Leprince,&nbsp;Messanvi Gbeassor,&nbsp;David Vaudry","doi":"10.1007/s12031-024-02222-6","DOIUrl":"10.1007/s12031-024-02222-6","url":null,"abstract":"<div><p>Plants are a valuable source of information for pharmacological research\u0000 and new drug discovery. The present study aimed to evaluate the neuroprotective\u0000 potential of the leaves of the medicinal plant <i>Sterculia\u0000 setigera</i>. In vitro, the effect of <i>Sterculia\u0000 setigera</i> leaves dry hydroethanolic extract (SSE) was tested on\u0000 cultured cerebellar granule neurons (CGN) survival when exposed to hydrogen peroxide\u0000 (H₂O₂) or 6-hydroxydopamine\u0000 (6-OHDA), using the viability probe fluorescein diacetate (FDA), a lactate\u0000 dehydrogenase (LDH) activity assay, an immunocytochemical staining against Gap 43,\u0000 and the quantification of the expression of genes involved in apoptosis, necrosis,\u0000 or oxidative stress. In vivo, the effect of intraperitoneal (ip) injection of SSE\u0000 was assessed on the developing brain of 8-day-old Wistar rats exposed to ethanol\u0000 neurotoxicity by measuring caspase-3 activity on cerebellum homogenates, the\u0000 expression of some genes in tissue extracts, the thickness of cerebellar cortical\u0000 layers and motor coordination. In vitro, SSE protected CGN against\u0000 H₂O₂ and 6-OHDA-induced cell death\u0000 at a dose of 10 µg/mL, inhibited the expression of genes <i>Casp3</i> and <i>Bad</i>, and upregulated\u0000 the expression of <i>Cat</i> and <i>Gpx7</i>. In vivo, SSE significantly blocked the deleterious effect of\u0000 ethanol by reducing the activity of caspase-3, inhibiting the expression of\u0000 <i>Bax</i> and <i>Tp53</i>, preventing the reduction of the thickness of the internal\u0000 granule cell layer of the cerebellar cortex, and restoring motor functions.\u0000 <i>Sterculia setigera</i> exerts neuroactive\u0000 functions as claimed by traditional medicine and should be a good candidate for the\u0000 development of a neuroprotective treatment against neurodegenerative\u0000 diseases.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615695","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}

{"title":"Integrating Multi-omics Data for Alzheimer’s Disease to Explore Its Biomarkers Via the Hypergraph-Regularized Joint Deep Semi-Non-Negative Matrix Factorization Algorithm","authors":"Kun Tu,&nbsp;Wenhui Zhou,&nbsp;Shubing Kong","doi":"10.1007/s12031-024-02211-9","DOIUrl":"10.1007/s12031-024-02211-9","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder. Its etiology may be associated with genetic, environmental, and lifestyle factors. With the advancement of technology, the integration of genomics, transcriptomics, and imaging data related to AD allows simultaneous exploration of molecular information at different levels and their interaction within the organism. This paper proposes a hypergraph-regularized joint deep semi-non-negative matrix factorization (HR-JDSNMF) algorithm to integrate positron emission tomography (PET), single-nucleotide polymorphism (SNP), and gene expression data for AD. The method employs matrix factorization techniques to nonlinearly decompose the original data at multiple layers, extracting deep features from different omics data, and utilizes hypergraph mining to uncover high-order correlations among the three types of data. Experimental results demonstrate that this approach outperforms several matrix factorization-based algorithms and effectively identifies multi-omics biomarkers for AD. Additionally, single-cell RNA sequencing (scRNA-seq) data for AD were collected, and genes within significant modules were used to categorize different types of cell clusters into high and low-risk cell groups. Finally, the study extensively explores the differences in differentiation and communication between these two cell types. The multi-omics biomarkers unearthed in this study can serve as valuable references for the clinical diagnosis and drug target discovery for AD. The realization of the algorithm in this paper code is available at https://github.com/ShubingKong/HR-JDSNMF.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563159","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}

{"title":"Transcriptome and Animal Model Integration Reveals Inhibition of Calcium Homeostasis-Associated Gene ITPKB Alleviates Amyloid Plaque Deposition","authors":"Yufei Hu,&nbsp;Zijun Zhao,&nbsp;Fang Xu,&nbsp;Xiaoqin Ren,&nbsp;Menglin Liu,&nbsp;Zilei Zheng,&nbsp;Qiujun Wang","doi":"10.1007/s12031-024-02221-7","DOIUrl":"10.1007/s12031-024-02221-7","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a severe neurological illness that causes memory loss and is a global problem. The calcium hypothesis recently steadily evolved in AD. The prospective targets for calcium homeostasis therapy, however, are limited, and gene expression-level research connected to calcium homeostasis in AD remains hazy. In this study, we analyzed the microarray dataset (GSE132903) taken from the Gene Expression Omnibus (GEO) database to investigate calcium homeostasis-related genes for AD. Using immunoblot analysis, we examined the association of ITPKB with inflammation in AD. Additionally, the immunofluorescence technique was employed to assess the impact of pharmacological inhibition of ITPKB on the amyloid-β (Aβ) plaque deposition in APP/PS1 mice. This article’s further exploration of calcium homeostasis-related genes has propelled the validation of the calcium homeostasis theory in AD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563060","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}

{"title":"Knockdown siRNA Targeting GPR55 Reveals Significant Differences Between the Anti-inflammatory Actions of KLS-13019 and Cannabidiol","authors":"Douglas E. Brenneman,&nbsp;William A. Kinney,&nbsp;Mark E. McDonnell,&nbsp;Michael J. Ippolito,&nbsp;Sara Jane Ward","doi":"10.1007/s12031-024-02217-3","DOIUrl":"10.1007/s12031-024-02217-3","url":null,"abstract":"<div><p>KLS-13019 was reported previously to reverse paclitaxel-induced mechanical allodynia in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). Recent studies demonstrated that paclitaxel-induced increases in inflammatory markers (GPR55, NLRP3, and IL-1β) of dorsal root ganglion (DRG) cultures were shown to be reversed by KLS-13019 treatment. The mechanism of action for KLS-13019-mediated reversal of paclitaxel-induced neuroinflammation now has been explored using GPR55 siRNA. Pre-treatment of DRG cultures with GPR55 siRNA produced a 21% decrease of immunoreactive (IR) area for GPR55 in cell bodies and a 59% decrease in neuritic IR area, as determined by high-content imaging. Using a 24-h reversal treatment paradigm, paclitaxel-induced increases in the inflammatory markers were reversed back to control levels after KLS-3019 treatment. Decreases in these inflammatory markers produced by KLS-13019 were significantly attenuated by GPR55 siRNA co-treatment, with mean IR area responses being attenuated by 56% in neurites and 53% in cell bodies. These data indicate that the percentage decreases in siRNA-mediated attenuation of KLS-13019-related efficacy on the inflammatory markers were similar to the percentage knockdown observed for neuritic GPR55 IR area. Similar studies conducted with cannabidiol (CBD), the parent compound of KLS-13019, produced low efficacy (25%) reversal of all inflammatory markers that were poorly attenuated (29%) by GPR55 siRNA. CBD was shown previously to be ineffective in reversing paclitaxel-induced mechanical allodynia. The present studies indicated significant differences between the anti-inflammatory properties of KLS-13019 and CBD which may play a role in their observed differences in the reversibility of mechanical allodynia in a mouse model of CIPN.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563210","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}