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, n = 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 (p < 0.05) antioxidant enzyme activities such as SOD, CAT, GPx, GSH, and TSH and prevented increases (p < 0.05) 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.
{"title":"Prepubertal Repeated Berberine Supplementation Enhances Cerebrocerebellar Functions by Modulating Neurochemical and Behavioural Changes in Wistar Rats.","authors":"Solomon Owumi, Joseph Chimezie, Moses Otunla, Bayode Oluwawibe, Harieme Agbarogi, Mayowa Anifowose, Uche Arunsi, Olatunde Owoeye","doi":"10.1007/s12031-024-02250-2","DOIUrl":"https://doi.org/10.1007/s12031-024-02250-2","url":null,"abstract":"<p><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, n = 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 (p < 0.05) antioxidant enzyme activities such as SOD, CAT, GPx, GSH, and TSH and prevented increases (p < 0.05) 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>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"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}
Pub Date : 2024-07-20DOI: 10.1007/s12031-024-02248-w
Gang Lei, Xiangbo Wu, Shuijie Zhang, Xiaoyun Tong, Gang Zhou
Acupuncture is a traditional Chinese therapy with treating potential against cognitive dysfunction. MicroRNA-21-3p (miR-21-3p) is well characterized for its benefits on neural tissues. The current study hypothesizes that the acupuncture aiming "Du" channel could attenuate IS-induced neural disorders by modulating the function of REST/miR-21-3p axis. Complications associated with IS are induced by a middle cerebral artery occlusion (MCAO) model in vivo. The disorders are then handled with the acupuncture with nimodipine as the positive control. It is found that the acupuncture improved cognitive function, reduced brain apoptosis, and increased the viable neuron number of model rats. Additionally, the production of cytokines is also suppressed by the acupuncture. At the molecular level, the level of miR-21-3p was up-regulated, while the level of REST was down-regulated by the acupuncture. The changes in miR-REST/21-3p contributed to the inhibition of PDCD4. Collectively, the findings in the current study highlight that miR-21-3p is associated with the anti-IS function of the acupuncture, which is mediated by the inhibition of REST.
针灸是一种具有治疗认知功能障碍潜力的传统中医疗法。微RNA-21-3p(miR-21-3p)对神经组织的益处已被证实。本研究假设,针刺 "杜 "字穴可通过调节REST/miR-21-3p轴的功能,减轻IS诱发的神经紊乱。IS相关并发症是由体内大脑中动脉闭塞(MCAO)模型诱发的。然后以尼莫地平为阳性对照,通过针灸治疗这些并发症。结果发现,针灸改善了模型大鼠的认知功能,减少了大脑凋亡,增加了存活神经元的数量。此外,针灸还抑制了细胞因子的产生。在分子水平上,针灸上调了 miR-21-3p 的水平,下调了 REST 的水平。miR-REST/21-3p 的变化有助于抑制 PDCD4。综上所述,本研究的结果表明,miR-21-3p 与针灸的抗 IS 功能有关,而针灸的抗 IS 功能是通过抑制 REST 介导的。
{"title":"Acupuncture Therapy Modulating \"Du\" Channel Attenuates Ischemic Stroke-induced Disorders by Modulating REST-mediated miR-21/PDCD4 Signaling Transduction.","authors":"Gang Lei, Xiangbo Wu, Shuijie Zhang, Xiaoyun Tong, Gang Zhou","doi":"10.1007/s12031-024-02248-w","DOIUrl":"10.1007/s12031-024-02248-w","url":null,"abstract":"<p><p>Acupuncture is a traditional Chinese therapy with treating potential against cognitive dysfunction. MicroRNA-21-3p (miR-21-3p) is well characterized for its benefits on neural tissues. The current study hypothesizes that the acupuncture aiming \"Du\" channel could attenuate IS-induced neural disorders by modulating the function of REST/miR-21-3p axis. Complications associated with IS are induced by a middle cerebral artery occlusion (MCAO) model in vivo. The disorders are then handled with the acupuncture with nimodipine as the positive control. It is found that the acupuncture improved cognitive function, reduced brain apoptosis, and increased the viable neuron number of model rats. Additionally, the production of cytokines is also suppressed by the acupuncture. At the molecular level, the level of miR-21-3p was up-regulated, while the level of REST was down-regulated by the acupuncture. The changes in miR-REST/21-3p contributed to the inhibition of PDCD4. Collectively, the findings in the current study highlight that miR-21-3p is associated with the anti-IS function of the acupuncture, which is mediated by the inhibition of REST.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730937","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}
Pub Date : 2024-07-18DOI: 10.1007/s12031-024-02246-y
Joseph Levine, Illana Gozes
{"title":"Editorial: The Current Categorical Concept of Schizophrenia is Inadequate: Should we Look at the Current State of Affairs for Compensatory Processes?","authors":"Joseph Levine, Illana Gozes","doi":"10.1007/s12031-024-02246-y","DOIUrl":"https://doi.org/10.1007/s12031-024-02246-y","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632265","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}
Pub Date : 2024-07-17DOI: 10.1007/s12031-024-02243-1
Fusheng Wei, Ting Chen, Yuanlu Huang, Yuxuan Yang, Xiaoe Cheng, Lei Yang
The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72 mol/L), ZD7288 (50 μmol/L), and KN-62 (10 μmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.
{"title":"Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.","authors":"Fusheng Wei, Ting Chen, Yuanlu Huang, Yuxuan Yang, Xiaoe Cheng, Lei Yang","doi":"10.1007/s12031-024-02243-1","DOIUrl":"10.1007/s12031-024-02243-1","url":null,"abstract":"<p><p>The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72 mol/L), ZD7288 (50 μmol/L), and KN-62 (10 μmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625555","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}
Pub Date : 2024-07-12DOI: 10.1007/s12031-024-02229-z
Lei Li, Ying Wang
Ischemic stroke is the leading cause of long-term disability in adults, accounting for 80% of stroke cases. Diffusion weighted imaging (DWI) examination is the main test for acute ischemic stroke, but in recent years, several studies have shown that some patients show negative DWI examination after the onset of ischemic stroke with symptoms of significant neurological deficits. In this study, we investigated potential biomarkers related to immune metabolism in the peripheral blood of DWI-negative versus DWI-positive patients after ischemic stroke and explored their possible regulatory processes in ischemic stroke. The datasets related to ischemic stroke were downloaded from the GEO database, immune-related genes and metabolism-related genes were obtained from the ImmPort database and MSigDB database, respectively, and immune-related differential genes were obtained based on immune scores using the algorithm of the R software package "GSVA." Candidate genes were selected based on intersections, hub genes were screened using the algorithm in Cytoscape software, and finally, GeneMANIA analysis, GSEA enrichment analysis, subcellular localization, gene transcription factor and gene-drug interaction networks, and disease correlation analyses were performed for the hub genes. Five hub genes (GART, TYMS, PPAT, CTPS1, and PAICS) were obtained by PPI network analysis and software analysis. Among them, PPAT and PAICS may be the real hub genes with consistent and significantly differentiated results from the discovery and validation sets. The functions of these hub genes may be related to pathways such as nucleotide biosynthetic processes. The constructed hub gene ceRNA network showed that hsa-10a-5p is the key miRNA connecting PAICS and multiple lncRNAs in this study. Differential genes related to immunity and metabolism in DWI-negative and DWI-positive patients after IS were identified using bioinformatics analysis, and their pathways and related TF-RNAs, miRNAs, and lncRNAs were identified. These genes may be considered effective targets for the diagnosis and treatment of ischemic stroke.
{"title":"Identification of Potential Biomarkers for Patients with DWI-Negative Ischemic Stroke.","authors":"Lei Li, Ying Wang","doi":"10.1007/s12031-024-02229-z","DOIUrl":"10.1007/s12031-024-02229-z","url":null,"abstract":"<p><p>Ischemic stroke is the leading cause of long-term disability in adults, accounting for 80% of stroke cases. Diffusion weighted imaging (DWI) examination is the main test for acute ischemic stroke, but in recent years, several studies have shown that some patients show negative DWI examination after the onset of ischemic stroke with symptoms of significant neurological deficits. In this study, we investigated potential biomarkers related to immune metabolism in the peripheral blood of DWI-negative versus DWI-positive patients after ischemic stroke and explored their possible regulatory processes in ischemic stroke. The datasets related to ischemic stroke were downloaded from the GEO database, immune-related genes and metabolism-related genes were obtained from the ImmPort database and MSigDB database, respectively, and immune-related differential genes were obtained based on immune scores using the algorithm of the R software package \"GSVA.\" Candidate genes were selected based on intersections, hub genes were screened using the algorithm in Cytoscape software, and finally, GeneMANIA analysis, GSEA enrichment analysis, subcellular localization, gene transcription factor and gene-drug interaction networks, and disease correlation analyses were performed for the hub genes. Five hub genes (GART, TYMS, PPAT, CTPS1, and PAICS) were obtained by PPI network analysis and software analysis. Among them, PPAT and PAICS may be the real hub genes with consistent and significantly differentiated results from the discovery and validation sets. The functions of these hub genes may be related to pathways such as nucleotide biosynthetic processes. The constructed hub gene ceRNA network showed that hsa-10a-5p is the key miRNA connecting PAICS and multiple lncRNAs in this study. Differential genes related to immunity and metabolism in DWI-negative and DWI-positive patients after IS were identified using bioinformatics analysis, and their pathways and related TF-RNAs, miRNAs, and lncRNAs were identified. These genes may be considered effective targets for the diagnosis and treatment of ischemic stroke.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589338","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}
Pub Date : 2024-07-12DOI: 10.1007/s12031-024-02247-x
Masum Öztürk, Fatma Subaşı Turgut, Davut Akbalık, Mustafa Erhan Demirkıran, İbrahim Kaplan
Erythropoietin (EPO) has neuroprotective effects by increasing oxidative stress resistance and stabilizing redox balance. Ischemic-modified albumin (IMA) is a product of protein oxidation, and recent evidence suggests that IMA can be used as an indicator of oxidative damage. This study aimed to investigate serum EPO and IMA levels in obsessive-compulsive disorder (OCD) patients and to investigate the relationship between EPO and IMA levels and clinical variables such as disease duration and disease severity. A total of 68 adolescents (11-18 years old), including 35 OCD patients (18 males/17 females) and 33 healthy controls (14 males/19 females) without comorbid disorders matched for age, gender, and BMI, were included in the study. The enzyme-amplified chemiluminescence technique determined serum EPO levels, and serum IMA levels were determined by the spectrophotometric method. Serum EPO levels were lower in OCD patients compared to healthy controls (p = 0.002; Z = - 3.123), and serum IMA levels (ABSU) were significantly higher in the OCD group (p = 0.005). A significant positive correlation was found between IMA levels and the duration of OCD symptoms (p = 0.015, r = 0.409). The study's findings contribute to the growing body of evidence implicating inflammatory and oxidative processes in the pathogenesis of OCD. The potential of EPO and IMA levels as diagnostic biomarkers for OCD aligns with the ongoing efforts to identify reliable biological markers for the disorder. The positive correlation of IMA levels with the duration of OCD shows the importance of early detection of oxidative damage.
促红细胞生成素(EPO)可增强抗氧化应激能力并稳定氧化还原平衡,从而起到保护神经的作用。缺血修饰白蛋白(IMA)是蛋白质氧化的产物,最近的证据表明,IMA可作为氧化损伤的指标。本研究旨在调查强迫症(OCD)患者的血清 EPO 和 IMA 水平,并研究 EPO 和 IMA 水平与病程和疾病严重程度等临床变量之间的关系。研究共纳入了 68 名青少年(11-18 岁),包括 35 名强迫症患者(18 名男性/17 名女性)和 33 名无合并症的健康对照组(14 名男性/19 名女性)(年龄、性别和体重指数均匹配)。采用酶扩增化学发光技术测定血清 EPO 水平,采用分光光度法测定血清 IMA 水平。与健康对照组相比,强迫症患者的血清 EPO 水平较低(p = 0.002;Z = - 3.123),而强迫症组的血清 IMA 水平(ABSU)明显较高(p = 0.005)。IMA水平与强迫症症状持续时间之间存在明显的正相关(p = 0.015,r = 0.409)。越来越多的证据表明,炎症和氧化过程与强迫症的发病机制有关。EPO和IMA水平有可能成为强迫症的诊断生物标志物,这与目前为确定强迫症的可靠生物标志物所做的努力不谋而合。IMA 水平与强迫症持续时间的正相关性表明了早期检测氧化损伤的重要性。
{"title":"Serum Erythropoietin and Ischemic-Modified Albumin Levels in Adolescents with Obsessive-Compulsive Disorder.","authors":"Masum Öztürk, Fatma Subaşı Turgut, Davut Akbalık, Mustafa Erhan Demirkıran, İbrahim Kaplan","doi":"10.1007/s12031-024-02247-x","DOIUrl":"10.1007/s12031-024-02247-x","url":null,"abstract":"<p><p>Erythropoietin (EPO) has neuroprotective effects by increasing oxidative stress resistance and stabilizing redox balance. Ischemic-modified albumin (IMA) is a product of protein oxidation, and recent evidence suggests that IMA can be used as an indicator of oxidative damage. This study aimed to investigate serum EPO and IMA levels in obsessive-compulsive disorder (OCD) patients and to investigate the relationship between EPO and IMA levels and clinical variables such as disease duration and disease severity. A total of 68 adolescents (11-18 years old), including 35 OCD patients (18 males/17 females) and 33 healthy controls (14 males/19 females) without comorbid disorders matched for age, gender, and BMI, were included in the study. The enzyme-amplified chemiluminescence technique determined serum EPO levels, and serum IMA levels were determined by the spectrophotometric method. Serum EPO levels were lower in OCD patients compared to healthy controls (p = 0.002; Z = - 3.123), and serum IMA levels (ABSU) were significantly higher in the OCD group (p = 0.005). A significant positive correlation was found between IMA levels and the duration of OCD symptoms (p = 0.015, r = 0.409). The study's findings contribute to the growing body of evidence implicating inflammatory and oxidative processes in the pathogenesis of OCD. The potential of EPO and IMA levels as diagnostic biomarkers for OCD aligns with the ongoing efforts to identify reliable biological markers for the disorder. The positive correlation of IMA levels with the duration of OCD shows the importance of early detection of oxidative damage.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589339","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}
Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI.
{"title":"Regulation of MicroRNAs After Spinal Cord Injury in Adult Zebrafish.","authors":"Wenyuan Shen, Jun Cai, Jinze Li, Wenchang Li, Pengcheng Shi, Xiumei Zhao, Shiqing Feng","doi":"10.1007/s12031-024-02242-2","DOIUrl":"https://doi.org/10.1007/s12031-024-02242-2","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578652","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}
Pub Date : 2024-07-10DOI: 10.1007/s12031-024-02239-x
Jozsef Gal, Calvin Vary, Carlos A Gartner, Gregory A Jicha, Erin L Abner, Yulica S Ortega, Ibrahim Choucair, Donna M Wilcock, Ruth S Nelson, Peter T Nelson
Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management. Participants (n = 29) had been autopsied and had antemortem CSF draws in a longitudinal cohort of older adults at the University of Kentucky AD Research Center. Cases were designated as LATE-NC + if they had LATE-NC stage > 1 (n = 9); the remaining 20 cases were designated LATE-NC-. This convenience sample of CSF specimens was analyzed in two separate processes: From one group, aliquots were depleted of highly abundant proteins using affinity spin columns. Tryptic digests of sample proteins were subjected to liquid chromatographic separation and mass spectrometry. Relative quantification was performed using Sciex software. Peptides referent to a total of 949 proteins were identified in the samples depleted of abundant proteins, and 820 different proteins were identified in the non-depleted samples. When the Bonferroni/false-discovery statistical correction was applied to account for having made multiple comparison tests, only 4 proteins showed differential expression (LATE-NC + vs LATE-NC-) in the non-depleted samples (RBP4, MIF, IGHG3, and ITM2B). Post hoc western blots confirmed that RBP4 expression was higher in the LATE-NC + cases at the group level. In summary, an exploratory assessment of proteomes of autopsy-confirmed LATE-NC and non-LATE-NC CSF did not demonstrate a clear-cut proteomic fingerprint that distinguished the two groups. There was, however, an increase in RBP4 protein levels in CSF from LATE-NC cases.
与痴呆症相关的常见神经病理变化包括阿尔茨海默病神经病理变化(ADNC)和边缘系统为主的年龄相关 TDP-43 脑病神经病理变化(LATE-NC)。生物流体蛋白质组学为了解痴呆症的病理生物学提供了一个窗口,生物流体检测的信息有助于指导临床治疗。肯塔基大学老年痴呆症研究中心(University of Kentucky AD Research Center)的老年人纵向队列中的参与者(n = 29)均接受过尸检,并在死前提取了脑脊液。如果病例的 LATE-NC 阶段大于 1(n = 9),则将其命名为 LATE-NC +;其余 20 个病例命名为 LATE-NC-。对这一方便取样的 CSF 标本进行了两个不同的分析过程:其中一组样本的等分样品使用亲和旋柱去除高含量蛋白质。对样本蛋白质的胰蛋白酶消化物进行液相色谱分离和质谱分析。使用 Sciex 软件进行相对定量。在去除了高含量蛋白质的样本中,共鉴定出 949 种蛋白质的肽段,而在未去除了高含量蛋白质的样本中,则鉴定出 820 种不同的蛋白质。当应用 Bonferroni/false-discovery 统计校正以考虑多重比较测试时,只有 4 种蛋白质(RBP4、MIF、IGHG3 和 ITM2B)在非耗尽样本中显示出差异表达(LATE-NC + vs LATE-NC-)。事后的 Western 印迹证实,在 LATE-NC + 病例组中,RBP4 的表达较高。总之,对尸检证实的 LATE-NC 和非 LATE-NC CSF 蛋白质组的探索性评估并未显示出区分两组的明确蛋白质组指纹。不过,LATE-NC病例CSF中的RBP4蛋白水平有所增加。
{"title":"Exploratory Mass Spectrometry of Cerebrospinal Fluid from Persons with Autopsy-Confirmed LATE-NC.","authors":"Jozsef Gal, Calvin Vary, Carlos A Gartner, Gregory A Jicha, Erin L Abner, Yulica S Ortega, Ibrahim Choucair, Donna M Wilcock, Ruth S Nelson, Peter T Nelson","doi":"10.1007/s12031-024-02239-x","DOIUrl":"10.1007/s12031-024-02239-x","url":null,"abstract":"<p><p>Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management. Participants (n = 29) had been autopsied and had antemortem CSF draws in a longitudinal cohort of older adults at the University of Kentucky AD Research Center. Cases were designated as LATE-NC + if they had LATE-NC stage > 1 (n = 9); the remaining 20 cases were designated LATE-NC-. This convenience sample of CSF specimens was analyzed in two separate processes: From one group, aliquots were depleted of highly abundant proteins using affinity spin columns. Tryptic digests of sample proteins were subjected to liquid chromatographic separation and mass spectrometry. Relative quantification was performed using Sciex software. Peptides referent to a total of 949 proteins were identified in the samples depleted of abundant proteins, and 820 different proteins were identified in the non-depleted samples. When the Bonferroni/false-discovery statistical correction was applied to account for having made multiple comparison tests, only 4 proteins showed differential expression (LATE-NC + vs LATE-NC-) in the non-depleted samples (RBP4, MIF, IGHG3, and ITM2B). Post hoc western blots confirmed that RBP4 expression was higher in the LATE-NC + cases at the group level. In summary, an exploratory assessment of proteomes of autopsy-confirmed LATE-NC and non-LATE-NC CSF did not demonstrate a clear-cut proteomic fingerprint that distinguished the two groups. There was, however, an increase in RBP4 protein levels in CSF from LATE-NC cases.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578632","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}
Circular RNAs (circRNAs) are a subclass of non-coding RNAs which have demonstrated potential as biomarkers for Alzheimer's disease (AD). In this study, we conducted a comprehensive exploration of the circRNA transcriptome within AD brain tissues. Specifically, we assessed circRNA expression patterns in the dorsolateral prefrontal cortex collected from nine AD-afflicted individuals and eight healthy controls. Utilising two circRNA detection tools, CIRI2 and CIRCexplorer2, we detected thousands of circRNAs and performed a differential expression analysis. CircRNAs which exhibited statistically significantly differential expression were identified as AD-specific differentially expressed circRNAs. Notably, our investigation revealed 120 circRNAs with significant upregulation and 1325 circRNAs displaying significant downregulation in AD brains when compared to healthy brain tissue. Additionally, we explored the expression profiles of the linear RNA counterparts corresponding to differentially expressed circRNAs in AD-afflicted brains and discovered that the linear RNA counterparts exhibited no significant changes in the levels of expression. We used CRAFT tool to predict that circUBE4B had potential to target miRNA named as hsa-miR-325-5p, ultimately regulated CD44 gene. This study provides a comprehensive overview of differentially expressed circRNAs in the context of AD brains, underscoring their potential as molecular biomarkers for AD. These findings significantly enhance our comprehension of AD's underlying pathophysiological mechanisms, offering promising avenues for future diagnostic and therapeutic developments.
{"title":"Investigation of the Circular Transcriptome in Alzheimer's Disease Brain.","authors":"Yulan Gao, Si-Mei Xu, Yuning Cheng, Konii Takenaka, Grace Lindner, Michael Janitz","doi":"10.1007/s12031-024-02236-0","DOIUrl":"10.1007/s12031-024-02236-0","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a subclass of non-coding RNAs which have demonstrated potential as biomarkers for Alzheimer's disease (AD). In this study, we conducted a comprehensive exploration of the circRNA transcriptome within AD brain tissues. Specifically, we assessed circRNA expression patterns in the dorsolateral prefrontal cortex collected from nine AD-afflicted individuals and eight healthy controls. Utilising two circRNA detection tools, CIRI2 and CIRCexplorer2, we detected thousands of circRNAs and performed a differential expression analysis. CircRNAs which exhibited statistically significantly differential expression were identified as AD-specific differentially expressed circRNAs. Notably, our investigation revealed 120 circRNAs with significant upregulation and 1325 circRNAs displaying significant downregulation in AD brains when compared to healthy brain tissue. Additionally, we explored the expression profiles of the linear RNA counterparts corresponding to differentially expressed circRNAs in AD-afflicted brains and discovered that the linear RNA counterparts exhibited no significant changes in the levels of expression. We used CRAFT tool to predict that circUBE4B had potential to target miRNA named as hsa-miR-325-5p, ultimately regulated CD44 gene. This study provides a comprehensive overview of differentially expressed circRNAs in the context of AD brains, underscoring their potential as molecular biomarkers for AD. These findings significantly enhance our comprehension of AD's underlying pathophysiological mechanisms, offering promising avenues for future diagnostic and therapeutic developments.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562338","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}
Pub Date : 2024-07-05DOI: 10.1007/s12031-024-02240-4
Richa Shrivastava, Puneet Gandhi, Sandeep K Sorte, Adesh Shrivastava
High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.
{"title":"Characterizing the Linkage of Systemic Hypoxia and Angiogenesis in High-Grade Glioma to Define the Changes in Tumor Microenvironment for Predicting Prognosis.","authors":"Richa Shrivastava, Puneet Gandhi, Sandeep K Sorte, Adesh Shrivastava","doi":"10.1007/s12031-024-02240-4","DOIUrl":"https://doi.org/10.1007/s12031-024-02240-4","url":null,"abstract":"<p><p>High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533268","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}