{"title":"Association of Telomere Length with Cognitive Impairment","authors":"Yevhenii Diukov, Natalia Bachinskaya, Andrii Dzobak, Victor Kholin, Yevheniia Kyriachenko, Oleksii Barsukov, Oksana Zabuha, Dmytro Krasnienkov","doi":"10.1007/s12031-023-02130-1","DOIUrl":"10.1007/s12031-023-02130-1","url":null,"abstract":"<div><p>Telomere attrition is attributed to Alzheimer’s disease (AD), major depressive disorder, stress levels, physical inactivity, short sleep duration, and reduced educational abilities. In this article, we tried to assess the association between the telomere length in peripheral blood leukocytes and level of cognitive impairment and its dependence on age and sex. Healthy subjects and patients with amnestic mild cognitive impairment (aMCI) and different AD stages were recruited in the study. All patients were assessed by the same standard diagnostic procedure, including neurological examination—Mini-Mental State Examination (MMSE). Blood samples from 66 subjects (18 men and 48 women, mean age 71.2 ± 0.56 years) were collected for DNA extraction from peripheral mononuclear cells (PBMC). Relative telomere length (RTL) was measured by monochrome multiplex polymerase chain reaction. The data obtained in the study indicate that RTL in PBMCs has a statistically significant association with MMSE score (<i>p</i> < 0.02). Moreover, the sex-specific difference was observed for the association between telomere length and various parameters of MMSE. Also, it has been found that a decrease in RTL by one unit is associated with an increase in the odds to get AD at a ratio of 2.54 (95% CI, 1.25 to 5.17). The results obtained in this research are in coherence with other studies that telomere length may be a valuable biomarker of cognitive decline. However, the potential need for longitudinal studies of telomere length, in order to estimate the influence of hereditary and environmental factors, remains.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"448 - 455"},"PeriodicalIF":3.1,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4259396","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":"RNA Sequencing of Intraoperative Peritumoral Tissues Reveals Potential Pathways Involved in Glioma-Related Seizures","authors":"Krishan Kumar, Vivek Dubey, Syeda S. Zaidi, Manjari Tripathi, Fouzia Siraj, Mehar Chand Sharma, P. Sarat Chandra, Ramesh Doddamani, Aparna Banerjee Dixit, Jyotirmoy Banerjee","doi":"10.1007/s12031-023-02125-y","DOIUrl":"10.1007/s12031-023-02125-y","url":null,"abstract":"<div><p>Tumor-induced changes in the peritumoral neocortex play a crucial role in generation of seizures. This study aimed to investigate the molecular mechanisms potentially involved in peritumoral epilepsy in low-grade gliomas (LGGs). Intraoperative peritumoral brain tissues resected from LGG patients with seizures (pGRS) or without seizures (pGNS) were used for RNA sequencing (RNA-seq). Comparative transcriptomics was performed to identify differentially expressed genes (DEGs) in pGRS compared to pGNS using deseq2 and edgeR packages (R). Gene set enrichment analysis (GSEA) using Gene Ontology terms and Kyoto Encyclopedia of Genes & Genomes (KEGG) pathways was performed using the clusterProfiler package (R). The expression of key genes was validated at the transcript and protein levels in the peritumoral region using real-time PCR and immunohistochemistry, respectively. A total of 1073 DEGs were identified in pGRS compared to pGNS, of which 559 genes were upregulated and 514 genes were downregulated (log2 fold-change ≥ 2, padj < 0.001). The DEGs in pGRS were highly enriched in the “Glutamatergic Synapse” and “Spliceosome” pathways, with increased expression of <i>GRIN2A (NR2A)</i>, <i>GRIN2B (NR2B)</i>, <i>GRIA1 (GLUR1)</i>, <i>GRIA3 (GLUR3)</i>, <i>GRM5</i>, <i>CACNA1C</i>, <i>CACNA1A</i>, and <i>ITPR2</i>. Moreover, increased immunoreactivity was observed for NR2A, NR2B, and GLUR1 proteins in the peritumoral tissues of GRS. These findings suggest that altered glutamatergic signaling and perturbed Ca<sup>2+</sup> homeostasis may be potential causes of peritumoral epilepsy in gliomas. This explorative study identifies important genes/pathways that merit further characterization for their potential involvement in glioma-related seizures.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"437 - 447"},"PeriodicalIF":3.1,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4091432","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 Profiling of Hippocampus After Cerebral Hypoperfusion in Mice","authors":"Zengyu Zhang, Zimin Guo, Pengpeng Jin, Hualan Yang, Mengting Hu, Yuan Zhang, Zhilan Tu, Shuangxing Hou","doi":"10.1007/s12031-023-02123-0","DOIUrl":"10.1007/s12031-023-02123-0","url":null,"abstract":"<div><p>Chronic cerebral hypoperfusion (CCH) is considered to be one of the major mechanism in the pathogenesis of vascular cognitive impairment (VCI). Increased inflammatory cells, particularly microglia, often parallel hypoperfusion-induced gray matter damage such as hippocampal lesions, but the exact mechanism remains largely unknown. To understand the pathological mechanisms, we analyzed hippocampus-specific transcriptome profiles after cerebral hypoperfusion. The mouse hypoperfusion model was induced by employing the 0.16/0.18 mm bilateral common carotid artery stenosis (BCAS) procedure. Cerebral blood flow (CBF) was assessed after 3-week hypoperfusion. Pathological changes were evaluated via hematoxylin staining and immunofluorescence staining. RNA-sequencing (RNA-seq) was performed using RNA samples of sham- or BCAS-operated mice, followed by quantitative real-time PCR (qRT-PCR) validation. We found that the 0.16/0.18 mm BCAS induced decreased CBF, hippocampal neuronal loss, and microglial activation. Furthermore, GSEA between sham and BCAS mice showed activation of interferon-beta signaling along with inflammatory immune responses. In addition, integrative analysis with published single-cell RNA-seq revealed that up-regulated differentially expressed genes (DEGs) were enriched in a distinct cell type of “microglia,” and down-regulated DEGs were enriched in “CA1 pyramidal,” not in “interneurons” or “S1 pyramidal.” This database of transcriptomic profiles of BCAS-hypoperfusion will be useful for future studies to explore potential targets for vascular cognitive dysfunction.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"423 - 436"},"PeriodicalIF":3.1,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-023-02123-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4089745","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 Efficacy of Fisetin Against VPA-Induced Autistic Neurobehavioral Alterations by Targeting Dysregulated Redox Homeostasis","authors":"Sweety Mehra, Aitizaz Ul Ahsan, Madhu Sharma, Muskan Budhwar, Mani Chopra","doi":"10.1007/s12031-023-02127-w","DOIUrl":"10.1007/s12031-023-02127-w","url":null,"abstract":"<div><p>Autism is a neurodevelopmental condition, and it's associated pathophysiology, viz., oxidative stress and altered cellular homeostasis, has been extensively intertwined with behavioral impairments. Therefore, targeting oxidative stress and redox cellular homeostasis could be beneficial in relieving autistic-like symptoms. For this purpose, we examined a library of nutraceutical compounds that led us to a bioflavonoid fisetin. Autism-like neurobehavior was induced by subjecting the pregnant rodents to valproic acid at the time of neural tube closure (GD12.5). In this novel study, fisetin was evaluated for its neuroprotective potential at gestational (GD13 until delivery) and post-weaning developmental windows (PND 23–32) in VPA-induced rodent model of autism. Developmental VPA exposure increased intracellular ROS production, oxidative stress, altered AChE and ATPases in brain regions, and induced autistic-like behavioral impairments (social, repetitive, stereotyped, and sensorimotor). The present findings suggested that gestational and post-weaning fisetin treatment significantly improved the behavioral impairments by attenuating elevated oxidative stress, ROS, lipid peroxidation, and re-establishing redox homeostasis. Also, it effectively reinstated the reduced levels of endogenous antioxidants, glutathione, AChE, and ATPases by its antioxidant potential. Therefore, fisetin with its properties could be used as a potential therapeutic agent in overcoming the symptoms associated with autism.</p><h3>Graphical Abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"403 - 422"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4038555","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":"Gene Panel Sequencing Analysis Revealed a Strong Contribution of Rare Coding Variants to the Risk of Parkinson’s Disease in Sporadic Moroccan Patients","authors":"Imane Smaili, Houyam Tibar, Mounia Rahmani, Najlaa Machkour, Rachid Razine, Hajar Naciri Darai, Naima Bouslam, Ali Benomar, Wafa Regragui, Ahmed Bouhouche","doi":"10.1007/s12031-023-02128-9","DOIUrl":"10.1007/s12031-023-02128-9","url":null,"abstract":"<div><p>Parkinson’s disease (PD) is a neurodegenerative movement disorder which can be either familial or sporadic. While it is well known that monogenic mutations are not a very common cause of PD, GWAS studies have shown that an additional fraction of the PD heritability could be explained by rare or common variants. To identify the rare variants that could influence the risk of PD in the Moroccan population, a cohort of 94 sporadic PD patients negative for the <i>LRRK2</i> G2019S mutation was subjected to NGS gene panel sequencing, and gene dosage using the MLPA method. Mean age of onset at enrollment was 51.7 ± 11.51 years, and 60% of patients were men. We identified 70 rare variants under 0.5% of frequency in 16 of the 20 genes analyzed, of which 7 were novel. Biallelic disease-causing variants in genes with recessive inheritance were found in 5 PD cases (5.31%), whereas 13 patients (13.8%) carried likely pathogenic variants in genes with dominant inheritance. Moreover, 8 patients (8.5%) carried a single variant in <i>MAPT</i> or <i>POLG</i>, whereas co-occurrence of rare variants involving more than one gene was observed in 28 patients (30%). PD patients with variants in recessive genes had a younger mean age at onset than patients with dominant ones (33.40 (12.77) vs. 53.15 (6.63), <i>p</i> < 0.001), while their clinical features were similar. However, patients with rare variants in the risk factor genes or in more than one gene tended to have less resting tremor (<i>p</i> < 0.04), but more dystonia (<i>p</i> < 0.006) and dementia (<i>p</i> < 0.002) than those without any rare variants in known PD-associated genes. Our results showed a significant enrichment of rare variants particularly in <i>LRRK2</i>, <i>VPS13C</i>, <i>POLG</i>, and <i>MAPT</i> and underline their impact on the risk of sporadic form of the disease.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"391 - 402"},"PeriodicalIF":3.1,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5183676","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}
Riya Ben Patel, Akhilesh Kumar Bajpai, Kavitha Thirumurugan
{"title":"Differential Expression of MicroRNAs and Predicted Drug Target in Amyotrophic Lateral Sclerosis","authors":"Riya Ben Patel, Akhilesh Kumar Bajpai, Kavitha Thirumurugan","doi":"10.1007/s12031-023-02124-z","DOIUrl":"10.1007/s12031-023-02124-z","url":null,"abstract":"<div><p>ALS (Amyotrophic Lateral Sclerosis) is a rare type of neurodegenerative disease. It shows progressive degradation of motor neurons in the brain and spinal cord. At present, there is no treatment available that can completely cure ALS. The available treatments can only increase a patient’s life span by a few months. Recently, microRNAs (miRNAs), a sub-class of small non-coding RNAs have been shown to play an essential role in the diagnosis, prognosis, and therapy of ALS. Our study focuses on analyzing differential miRNA profiles and predicting drug targets in ALS using bioinformatics and computational approach. The study identifies eight highly differentially expressed miRNAs in ALS patients, four of which are novel. We identified 42 <i>hub</i> genes for these eight highly expressed miRNAs with Amyloid Precursor Protein (<i>APP)</i> as a candidate gene among them for highly expressed down-regulated miRNA, hsa-miR-455-3p using protein–protein interaction network and Cytoscape analysis. A novel association has been found between hsa-miR-455-3p/APP/serotonergic pathway using KEGG pathway analysis. Also, molecular docking studies have revealed curcumin as a potential drug target that may be used for the treatment of ALS. Thus, the present study has identified four novel miRNA biomarkers: hsa-miR-3613-5p, hsa-miR-24, hsa-miR-3064-5p, and hsa-miR-4455. There is a formation of a novel axis, hsa-miR-455-3p/APP/serotonergic pathway, and curcumin is predicted as a potential drug target for ALS.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"375 - 390"},"PeriodicalIF":3.1,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5164815","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 of Rab7B, But Not of Rab7A, Which Antagonistically Regulates Oligodendroglial Cell Morphological Differentiation, Recovers Tunicamycin-Induced Defective Differentiation in FBD-102b Cells","authors":"Nana Fukushima, Remina Shirai, Takanari Sato, Sayumi Nakamura, Arisa Ochiai, Yuki Miyamoto, Junji Yamauchi","doi":"10.1007/s12031-023-02117-y","DOIUrl":"10.1007/s12031-023-02117-y","url":null,"abstract":"<div><p>In the central nervous system (CNS), insulative myelin sheaths are generated from the differentiated plasma membranes of oligodendrocytes (oligodendroglial cells) and surround neuronal axons to achieve saltatory conduction. Despite the functional involvement of myelin sheaths in the CNS, the molecular mechanism by which oligodendroglial cells themselves undergo differentiation of plasma membranes remains unclear. It also remains to be explored whether their signaling mechanisms can be applied to treating diseases of the oligodendroglial cells. Here, we describe that Rab7B of Rab7 subfamily small GTPases negatively regulates oligodendroglial cell morphological differentiation using FBD-102b cells, which are model cells undergoing differentiation of oligodendroglial precursors. Knockdown of Rab7B or Rab7A by the respective specific siRNAs in cells positively or negatively regulated morphological differentiation, respectively. Consistently, these changes were supported by changes on differentiation- and myelination-related structural protein and protein kinase markers. We also found that knockdown of Rab7B has the ability to recover inhibition of morphological differentiation following tunicamycin-induced endoplasmic reticulum (ER) stress, which mimics one of the major molecular pathological causes of hereditary hypomyelinating disorders in oligodendroglial cells, such as Pelizaeus-Merzbacher disease (PMD). These results suggest that the respective molecules among very close Rab7 homologues exhibit differential roles in morphological differentiation and that knocking down Rab7B can recover defective differentiating phenotypes under ER stress, thereby adding Rab7B to the list of molecular therapeutic cues taking advantage of signaling mechanisms for oligodendroglial diseases like PMD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"363 - 374"},"PeriodicalIF":3.1,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5164817","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":"Spatial Distribution of Neurons Expressing Single, Double, and Triple Molecular Characteristics of Glutamatergic, Dopaminergic, or GABAergic Neurons in the Mouse Ventral Tegmental Area","authors":"Shaohua Ma, Hao Zhong, Xuemei Liu, Liping Wang","doi":"10.1007/s12031-023-02121-2","DOIUrl":"10.1007/s12031-023-02121-2","url":null,"abstract":"<div><p>The ventral tegmental area (VTA) is a heterogeneous midbrain area that plays a significant role in diverse neural processes such as reward, aversion, and motivation. The VTA contains three main neuronal populations, namely, dopamine (DA), γ-aminobutyric acid (GABA), and glutamate neurons, but some neurons exhibit combinatorial molecular characteristics of dopaminergic, GABAergic, or glutamatergic neurons. However, little information is available regarding detailed distribution of neurons with single, double, and triple molecular characteristics of glutamatergic, dopaminergic, or GABAergic neurons in mice. We present a topographical distribution map of three main neuronal populations expressing a single molecular characteristic of dopaminergic, GABAergic, or glutamatergic neurons, and four neuronal populations co-expressing double or triple molecular characteristics in combinatorial manners, in the mouse VTA, following analysis of triple fluorescent in situ hybridization for the simultaneous detection of tyrosine hydroxylase (TH, marker for dopaminergic neurons), vesicular glutamate transporter 2 (VGLUT2, marker for glutamatergic neurons), and glutamic acid decarboxylase 2 (GAD2, marker for GABAergic neurons) mRNA. We found that the vast majority of neurons expressed a single type of mRNA, and these neurons were intermingled with neurons co-expressing double or triple combinations of VGLUT2, TH, or GAD2 in the VTA. These seven neuronal populations were differentially distributed in the VTA sub-nuclei across the rostro-caudal and latero-medial axes. This histochemical study will lead to a deeper understanding of the complexity of neuronal molecular characteristics in different VTA sub-nuclei, and potentially facilitate clarification of diverse functions of the VTA.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"345 - 362"},"PeriodicalIF":3.1,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5057461","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}
Qiongni Zhu, Zhimin Zhu, Stephen James Renaud, Lei Hu, Ying Guo
{"title":"The Oncogenic Role of Cyclin-Dependent Kinase Inhibitor 2C in Lower-Grade Glioma","authors":"Qiongni Zhu, Zhimin Zhu, Stephen James Renaud, Lei Hu, Ying Guo","doi":"10.1007/s12031-023-02120-3","DOIUrl":"10.1007/s12031-023-02120-3","url":null,"abstract":"<div><p>Lower-grade gliomas (LGGs) are slow-growing, indolent tumors that usually affect younger patients and present a therapeutic challenge due to the heterogeneity of their clinical presentation. Dysregulation of cell cycle regulatory factors is implicated in the progression of many tumors, and drugs that target cell cycle machinery have shown efficacy as promising therapeutic approaches. To date, however, no comprehensive study has examined how cell cycle-related genes affect LGG outcomes. The cancer genome atlas (TCGA) data were used as the training set for differential analysis of gene expression and patient outcomes; the Chinese glioma genome atlas (CGGA) was used for validation. Levels of one candidate protein, cyclin-dependent kinase inhibitor 2C (<i>CDKN2C</i>), and its relationship to clinical prognosis were determined using a tissue microarray containing 34 LGG tumors. A nomogram was constructed to model the putative role of candidate factors in LGG. Cell type proportion analysis was performed to evaluate immune cell infiltration in LGG. Various genes encoding cell cycle regulatory factors showed increased expression in LGG and were significantly related to isocitrate dehydrogenase and chromosome arms 1p and 19q mutation status. <i>CDKN2C</i> expression independently predicted the outcome of LGG patients. High M2 macrophage values along with elevated <i>CDKN2C</i> expression were associated with poorer prognosis in LGG patients. <i>CDKN2C</i> plays an oncogenic role in LGG, which is associated with M2 macrophages.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"327 - 344"},"PeriodicalIF":3.1,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4944129","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 Sequencing of CeRNA Network Constructing in Status Epilepticus Mice Treated by Low-Frequency Repetitive Transcranial Magnetic Stimulation","authors":"Shaotian Zhang, Huihui Zou, Xiaopei Zou, Jiaqia Ke, Bofang Zheng, Xinrun Chen, Xianju Zhou, Jiana Wei","doi":"10.1007/s12031-023-02108-z","DOIUrl":"10.1007/s12031-023-02108-z","url":null,"abstract":"<div><p>It is shown that great progress was recently made in the treatment of repetitive transcranial magnetic stimulation (rTMS) for neurological and psychiatric diseases. This study aimed to address how rTMS exerted it therapeutic effects by regulating competitive endogenous RNAs (ceRNAs) of lncRNA-miRNA-mRNA. The distinction of lncRNA, miRNA and mRNA expression in male status epilepticus (SE) mice treated by two different ways, low-frequency rTMS (LF-rTMS) vs. sham rTMS, was analyzed by high-throughput sequencing. The Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. Gene–Gene Cross Linkage Network was established; pivotal genes were screened out. qRT-PCR was used to verify gene–gene interactions. Our results showed that there were 1615 lncRNAs, 510 mRNAs, and 17 miRNAs differentially which were expressed between the LF-rTMS group and the sham rTMS group. The expression difference of these lncRNAs, mRNAs, and miRNAs by microarray detection were consistent with the results by qPCR. GO functional enrichment showed that immune-associated molecular mechanisms, biological processes, and GABA-A receptor activity played a role in SE mice treated with LF-rTMS. KEGG pathway enrichment analysis revealed that differentially expressed genes were correlated to T cell receptor signaling pathway, primary immune deficiency and Th17 cell differentiation signaling pathway. Gene–gene cross linkage network was established on the basis of Pearson’s correlation coefficient and miRNA. In conclusion, LF-rTMS alleviates SE through regulating the GABA-A receptor activity transmission, improving immune functions, and biological processes, suggesting the underlying ceRNA molecular mechanisms of LF-rTMS treatment for epilepsy.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 4-5","pages":"316 - 326"},"PeriodicalIF":3.1,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-023-02108-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4135212","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}