NeuroMolecular Medicine最新文献

{"title":"Effect of 2-Week Naringin Supplementation on Neurogenesis and BDNF Levels in Ischemia-Reperfusion Model of Rats.","authors":"Esen Yilmaz, Gozde Acar, Ummugulsum Onal, Ender Erdogan, Abdulkerim Kasim Baltaci, Rasim Mogulkoc","doi":"10.1007/s12017-023-08771-0","DOIUrl":"10.1007/s12017-023-08771-0","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is the leading cause of mortality and disability worldwide with more than half of survivors living with serious neurological sequelae; thus, it has recently attracted a lot of attention in the field of medical study.</p><p><strong>Purpose: </strong>The aim of this study was to determine the effect of naringin supplementation on neurogenesis and brain-derived neurotrophic factor (BDNF) levels in the brain in experimental brain ischemia-reperfusion.</p><p><strong>Study design: </strong>The research was carried out on 40 male Wistar-type rats (10-12 weeks old) obtained from the Experimental Animals Research and Application Center of Selçuk University. Experimental groups were as follows: (1) Control group, (2) Sham group, (3) Brain ischemia-reperfusion group, (4) Brain ischemia-reperfusion + vehicle group (administered for 14 days), and (5) Brain ischemia-reperfusion + Naringin group (100 mg/kg/day administered for 14 days).</p><p><strong>Methods: </strong>In the ischemia-reperfusion groups, global ischemia was performed in the brain by ligation of the right and left carotid arteries for 30 min. Naringin was administered to experimental animals by intragastric route for 14 days following reperfusion. The training phase of the rotarod test was started 4 days before ischemia-reperfusion, and the test phase together with neurological scoring was performed the day before and 1, 7, and 14 days after the operation. At the end of the experiment, animals were sacrificed, and then hippocampus and frontal cortex tissues were taken from the brain. Double cortin marker (DCX), neuronal nuclear antigen marker (NeuN), and BDNF were evaluated in hippocampus and frontal cortex tissues by Real-Time qPCR analysis and immunohistochemistry methods.</p><p><strong>Results: </strong>While ischemia-reperfusion increased the neurological score values, DCX, NeuN, and BDNF levels decreased significantly after ischemia in the hippocampus and frontal cortex tissues. However, naringin supplementation restored the deterioration to a certain extent.</p><p><strong>Conclusion: </strong>The results of the study show that 2 weeks of naringin supplementation may have protective effects on impaired neurogenesis and BDNF levels after brain ischemia and reperfusion in rats.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060050","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":"Uncovering Sex-Specific Epigenetic Regulatory Mechanism Involving H3k9me2 in Neural Inflammation, Damage, and Recovery in the Internal Carotid Artery Occlusion Mouse Model.","authors":"Mydhili Radhakrishnan, Vincy Vijay, B Supraja Acharya, Papia Basuthakur, Shashikant Patel, Kalyani Soren, Arvind Kumar, Sumana Chakravarty","doi":"10.1007/s12017-023-08768-9","DOIUrl":"https://doi.org/10.1007/s12017-023-08768-9","url":null,"abstract":"<p><p>Cerebral ischemic stroke is one of the foremost global causes of death and disability. Due to inadequate knowledge in its sequential disease mechanisms, therapeutic efforts to mitigate acute ischemia-induced brain injury are limited. Recent studies have implicated epigenetic mechanisms, mostly histone lysine acetylation/deacetylation, in ischemia-induced neural damage and death. However, the role of lysine methylation/demethylation, another prevalent epigenetic mechanism in cerebral ischemia has not undergone comprehensive investigation, except a few recent reports, including those from our research cohort. Considering the impact of sex on post-stroke outcomes, we studied both male and female mice to elucidate molecular details using our recently developed Internal Carotid Artery Occlusion (ICAO) model, which induces mild to moderate cerebral ischemia, primarily affecting the striatum and ventral hippocampus. Here, we demonstrate for the first time that female mice exhibit faster recovery than male mice following ICAO, evaluated through neurological deficit score and motor coordination assessment. Furthermore, our investigation unveiled that dysregulated histone lysine demethylases (KDMs), particularly kdm4b/jmjd2b are responsible for the sex-specific variance in the modulation of inflammatory genes. Building upon our prior reportage blocking KDMs by DMOG (Dimethyloxalylglycine) and thus preventing the attenuation in H3k9me2 reduced the post-ICAO transcript levels of the inflammatory molecules and neural damage, our present study delved into investigating the differential role of H3k9me2 in the regulation of pro-inflammatory genes in female vis-à-vis male mice underlying ICAO-induced neural damage and recovery. Overall, our results reveal the important role of epigenetic mark H3k9me2 in mediating sex-specific sequential events in inflammatory response, elicited post-ICAO.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972774","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":"Effects of Chronic Hypertension on the Energy Metabolism of Cerebral Cortex Mitochondria in Normotensive and in Spontaneously Hypertensive Rats During Aging.","authors":"Roberto Federico Villa, Federica Ferrari, Antonella Gorini","doi":"10.1007/s12017-023-08772-z","DOIUrl":"10.1007/s12017-023-08772-z","url":null,"abstract":"<p><p>In this study the subcellular modifications undergone by cerebral cortex mitochondrial metabolism in chronic hypertension during aging were evaluated. The catalytic properties of regulatory energy-linked enzymes of Tricarboxylic Acid Cycle (TCA), Electron Transport Chain (ETC) and glutamate metabolism were assayed on non-synaptic mitochondria (FM, located in post-synaptic compartment) and on intra-synaptic mitochondria of pre-synaptic compartment, furtherly divided in \"light\" (LM) and \"heavy\" (HM) mitochondria, purified form cerebral cortex of normotensive Wistar Kyoto Rats (WKY) versus Spontaneously Hypertensive Rats (SHR) at 6, 12 and 18 months. During physiological aging, the metabolic machinery was differently expressed in pre- and post-synaptic compartments: LM and above all HM were more affected by aging, displaying lower ETC activities. In SHR at 6 months, FM and LM showed an uncoupling between TCA and ETC, likely as initial adaptive response to hypertension. During pathological aging, HM were particularly affected at 12 months in SHR, as if the adaptive modifications in FM and LM at 6 months granted a mitochondrial functional balance, while at 18 months all the neuronal mitochondria displayed decreased metabolic fluxes versus WKY. This study describes the effects of chronic hypertension on cerebral mitochondrial energy metabolism during aging through functional proteomics of enzymes at subcellular levels, i.e. in neuronal soma and synapses. In addition, this represents the starting point to envisage an experimental physiopathological model which could be useful also for pharmacological studies, to assess drug actions during the development of age-related pathologies that could coexist and/or are provoked by chronic hypertension.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932268","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":"Amelioration of Astrocyte-Mediated Neuroinflammation by EI-16004 Confers Neuroprotection in an MPTP-induced Parkinson's Disease Model.","authors":"Jaehoon Kim, Seulah Lee, Dong Geun Hong, Seonguk Yang, Cong So Tran, Jinsook Kwak, Min-Ju Kim, Thenmozhi Rajarathinam, Ki Wung Chung, Young-Suk Jung, Akihito Ishigami, Seung-Cheol Chang, Haeseung Lee, Hwayoung Yun, Jaewon Lee","doi":"10.1007/s12017-023-08769-8","DOIUrl":"10.1007/s12017-023-08769-8","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder that results in motor impairment due to dopaminergic neuronal loss. The pathology of PD is closely associated with neuroinflammation, which can be characterized by astrocyte activation. Thus, targeting the inflammatory response in astrocytes might provide a novel therapeutic approach. We conducted a luciferase assay on an in-house chemical library to identify compounds with anti-inflammatory effects capable of reducing MPP⁺-induced NF-κB activity in astrocytes. Among the compounds identified, EI-16004, a novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides, exhibited a significant anti-inflammatory effect by significantly reducing MPP⁺-induced astrocyte activation. Biochemical analysis and docking simulation indicated that EI-16004 inhibited the MPP⁺-induced phosphorylation of p65 by attenuating ERK phosphorylation, and EI-16004 reduced pro-inflammatory cytokine and chemokine levels in astrocytes. In vivo studies on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in male C57BL/6 mice showed that EI-16004 ameliorated motor impairment and protected against dopaminergic neuronal loss, and EI-16004 effectively mitigated the MPTP-induced astrocyte activation in striatum (STR) and substantia nigra (SN). These results indicate EI-16004 is a potential neuroprotective agent for the prevention and treatment of astrocyte-mediated neuroinflammatory conditions in PD.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642672","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":"Author Correction: Potential of Quercetin to Protect Cadmium Induced Cognitive Deficits in Rats by Modulating NMDA‑R Mediated Downstream Signaling and PI3K/AKT-Nrf2/ARE Signaling Pathways in Hippocampus.","authors":"Anugya Srivastava, Anima Kumari, Pankaj Jagdale, Anjaneya Ayanur, Aditya Bhushan Pant, Vinay Kumar Khanna","doi":"10.1007/s12017-023-08765-y","DOIUrl":"10.1007/s12017-023-08765-y","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680376","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":"Increased IL-6 Levels and the Upregulation of Iron Regulatory Biomarkers Contribute to the Progression of Japanese Encephalitis Virus Infection's Pathogenesis.","authors":"Anjali Singh, Sneha Ghildiyal, Prabhaker Mishra, Gajendra Singh, Himanshu Dandu, Alok Kumar","doi":"10.1007/s12017-023-08762-1","DOIUrl":"10.1007/s12017-023-08762-1","url":null,"abstract":"<p><p>Integrated analysis of iron regulatory biomarkers and inflammatory response could be an important strategy for Japanese encephalitis viral (JEV) infection disease management. In the present study, the inflammatory response was assessed by measuring serum Interleukin-6 (IL-6) levels using ELISA, and the transcription levels of iron homeostasis regulators were analyzed via RT-PCR. Furthermore, inter-individual variation in the transferrin gene was analyzed by PCR-RFLP and their association with clinical symptoms, susceptibility, severity, and outcomes was assessed through binary logistic regression and classification and regression tree (CART) analysis. Our findings revealed elevated levels of IL-6 in serum as well as increased expression of hepcidin (HAMP), transferrin (TF), and transferrin receptor-1 (TFR1) mRNA in JEV infection cases. Moreover, we found a genetic variation in TF (rs4481157) associated with clinical symptoms of meningoencephalitis. CART analysis indicates that individuals with the wild-type TF genotype are more susceptible to moderate JEV infection, while those with the homozygous type are in the high-risk group to develop a severe JEV condition. In summary, the study highlights that JEV infection induces alteration in both IL-6 levels and iron regulatory processes, which play pivotal roles in the development of JEV disease pathologies.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425509","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":"MicroRNAs as a Tool for Differential Diagnosis of Neuromuscular Disorders.","authors":"Nahla O Mousa, Ahmed Abdellatif, Nagia Fahmy, Hassan El-Fawal, Ahmed Osman","doi":"10.1007/s12017-023-08763-0","DOIUrl":"10.1007/s12017-023-08763-0","url":null,"abstract":"<p><p>Neuromuscular disorders (NMD) are a class of progressive disorders that are characterized by wasting of the muscles. Some of the disorders like Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), congenital muscular dystrophies (CMDs), limb-girdle muscular dystrophies (LGMD), and mild spinal muscular atrophy (SMA) type III share several presenting clinical features, and hence, diagnosis is usually a challenging task. In this study, the diagnostic potential of some species of microRNAs (miRNAs) that are known to play roles in normal and pathological contexts of myocytes (myomiRs) were evaluated to assess their potential in differential diagnosis of NMDs. In this study, seventy-four patients with different neuromuscular disorders along with thirty age-matched healthy control subjects were enrolled. Peripheral blood samples were collected from enrolled subjects followed by miRNA extraction and reverse transcription followed by quantification of the circulating levels of the studied miRNAs (miR-499, miR-206, miR-208a, miR-223, miR-191, miR-103a-3p, miR-103a-5p), by real-time PCR and statistical analysis. The data indicated that miR-499 level showed high circulating levels in DMD patients as well as in patients with other related disorders such as BMD. However, the levels of miR-499 were much higher in DMD patients and it can be used to diagnose DMD. In addition, miR-206 can selectively differentiate between DMD and all other disorders. The results also revealed that miR-208a and miR-223 were significantly dysregulated in SMA patients, and miR-103a-3p could distinguish DMD from BMD. The expression levels of some miRNA species can be utilized in the process of differential diagnosis of NMDs and can serve as a diagnostic biomarker, and such findings will pave the way towards generating targeted therapies.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10721695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680377","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":"Effect of GNE Mutations on Cytoskeletal Network Proteins: Potential Gateway to Understand Pathomechanism of GNEM","authors":"R. Yadav, Jyoti Oswalia, Anu Ghosh, R. Arya","doi":"10.1007/s12017-022-08711-4","DOIUrl":"https://doi.org/10.1007/s12017-022-08711-4","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46794766","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":"ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19","authors":"W. Ong, R. L. Satish, D. Herr","doi":"10.1007/s12017-022-08706-1","DOIUrl":"https://doi.org/10.1007/s12017-022-08706-1","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49501315","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":"Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes","authors":"I. S. Schädlich, J. H. Vienhues, A. Jander, Marius Piepke, T. Magnus, K. Lambertsen, B. Clausen, M. Gelderblom","doi":"10.1007/s12017-022-08709-y","DOIUrl":"https://doi.org/10.1007/s12017-022-08709-y","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49556921","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}