Journal of Molecular Neuroscience最新文献

{"title":"Valproate Administration to Adult 5xFAD Mice Upregulates Expression of Neprilysin and Improves Olfaction and Memory","authors":"Dmitrii S. Vasilev,&nbsp;Nadezhda M. Dubrovskaya,&nbsp;Natalia L. Tumanova,&nbsp;Aleksandr N. Tursunov,&nbsp;Natalia N. Nalivaeva","doi":"10.1007/s12031-024-02287-3","DOIUrl":"10.1007/s12031-024-02287-3","url":null,"abstract":"<div><p>It is well known that the development of neurodegeneration, and especially Alzheimer’s disease (AD), is often accompanied by impaired olfaction which precedes memory loss. A neuropeptidase neprilysin (NEP)—a principal amyloid-degrading enzyme in the brain—was also shown to be involved in olfactory signalling. Previously we have demonstrated that 5xFAD mice develop olfactory deficit by the age of 6 months which correlated with reduced NEP expression in the brain areas involved in olfactory signalling. The aim of this study was to analyse the effect of administration of a histone deacetylase inhibitor, valproic acid (VA), to adult 5xFAD mice on their olfaction and memory as well as on brain morphology and NEP expression in the parietal cortex (PC) and hippocampus (Hip). The data obtained demonstrated that administration of VA to 7-month-old mice (200 mg/kg of body weight) for 28 days resulted in improvement of their memory in the Morris water maze as well as olfaction in the odor preference and food search tests. This correlated with increased expression of NEP in the PC and Hip as well as a reduced number of amyloid plaques in these brain areas. This strongly suggests that NEP can be considered an important therapeutic target not only in AD but also in olfactory loss.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643620","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":"Investigation of Association Between Expression of DYX1C1, KIAA0319, and ROBO1 Genes and Specific Learning Disorder in Children and Adolescents","authors":"Burcu Bayyurt,&nbsp;Nil Özbilüm Şahin,&nbsp;Cansu Mercan Işık","doi":"10.1007/s12031-024-02288-2","DOIUrl":"10.1007/s12031-024-02288-2","url":null,"abstract":"<div><p>Specific learning disorder (SLD) is prevalent worldwide and is a complex disorder with variable symptoms and significant differences among individuals. Epigenetic markers may alter susceptibility to neurodevelopmental disorders (NDDs). Aberrant expression of protein-coding (mRNA) genes in this pathology shows that the detection of epigenetic molecular biomarkers is of increasing importance in the diagnosis and treatment of individuals with SLD. We compared gene expression level of <i>dyslexia susceptibility 1 candidate gene 1</i> (<i>DYX1C1</i>), <i>dyslexia-associated protein KIAA0319</i> (<i>KIAA0319</i>), and <i>roundabout guidance receptor 1</i> (<i>ROBO1</i>) between children with SLD and healthy children by performing quantitative polymerase chain reaction (qPCR). In addition, we evaluated these gene expressions of severe children with SLD compared to non-severe and male SLD children compared to females. The expression of the <i>DYX1C1</i>, <i>KIAA0319</i>, and <i>ROBO1</i> genes was statistically significantly upregulated in children with SLD (<i>P</i> &lt; 0.05*). <i>DYX1C1</i> was also upregulated in severe SLD children (<i>P</i> = 0.03*). In addition, <i>KIAA0319</i> and <i>ROBO1</i> genes were differentially expressed in male SLD children compared to females (<i>P</i> &lt; 0.05*). Furthermore, we found that <i>DYX1C1</i> and <i>ROBO1</i> genes significantly affect the likelihood of the SLD (respectively, <i>P</i> &lt; 0.001** and <i>P</i> = 0.007*). We expect that the findings provided from this study may contribute to the determination expression level of the relevant genes in the diagnosis, prognosis, and treatment of SLD. In addition, our findings could be a guide for future epigenetics studies on the use of the <i>DYX1C1</i>, <i>KIAA0319</i>, and <i>ROBO1</i> in therapeutic applications in the SLD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611764","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":"Identification of Novel Circular RNA Targets in Key Penumbra Region of Rats After Cerebral Ischemia-Reperfusion Injury","authors":"Jiabei Ye,&nbsp;Yudong Shan,&nbsp;Xiaohong Zhou,&nbsp;Tian Tian,&nbsp;Weijuan Gao","doi":"10.1007/s12031-023-02153-8","DOIUrl":"10.1007/s12031-023-02153-8","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) are abundantly and stably expressed in the brain of mammals and humans. Some circRNAs are implicated in ischemic stroke. Therefore, we aimed to detect how circRNAs change in the key penumbra area during cerebral ischemia-reperfusion (CI/R) injury. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), during which the permanent blocking period was 2 h and reperfusion time was 24 or 72 h. Then modified neurologic severity score (mNSS), triphenyl tetrazolium chloride (TTC) staining and HE staining were used to exhibiting damage between rats in different groups. The penumbra regions of all rats were dissected and total RNA was further processed for high-throughput sequencing. CircRNA expression profiles were screened and bioinformatics analyses were conducted to investigate these differentially expressed circRNAs. Some of them were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by the establishment of a circRNA-miRNA-mRNA network and the detection of their downstream molecules. A total of 99 and 98 circRNAs were differentially expressed at CI/R 24 h and CI/R 72 h, respectively. Notably, 21 circRNAs significantly changed at both reperfusion points. Three circRNAs, namely circ.7225, circ.5415, and circ.20623 were found to be associated with CI/R injury and might be preferred targets. Common downstream miR-298-5p and Bcl-3 were found to make up the circRNA-miRNA-mRNA network. Novel circRNA targets came to light in the penumbra of rats during CI/R injury and might establish the circRNA-miRNA-mRNA relationship, thus serving as potential biomarkers for ischemic stroke treatment.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"751 - 762"},"PeriodicalIF":3.1,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10188891","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":"Evaluating Gene Expression and Methylation Profiles of TCF4, MBP, and EGR1 in Peripheral Blood of Drug-Free Patients with Schizophrenia: Correlations with Psychopathology, Intelligence, and Cognitive Impairment","authors":"Fatemeh Yazarlou,&nbsp;Mobina Tabibian,&nbsp;Asaad Azarnezhad,&nbsp;Habib Sadeghi Rad,&nbsp;Leonard Lipovich,&nbsp;Golshid Sanati,&nbsp;Hamid Mostafavi Abdolmaleky,&nbsp;Fatemeh Alizadeh","doi":"10.1007/s12031-023-02150-x","DOIUrl":"10.1007/s12031-023-02150-x","url":null,"abstract":"<div><p>Discovery and validation of new, reliable diagnostic and predictive biomarkers for schizophrenia (SCZ) are an ongoing effort. Here, we assessed the mRNA expression and DNA methylation of the TCF4, MBP, and EGR1 genes in the blood of patients with SCZ and evaluated their relationships to psychopathology and cognitive impairments. Quantitative real-time PCR and quantitative methylation-specific PCR methods were used to assess the expression level and promoter DNA methylation status of these genes in 70 drug-free SCZ patients and 72 healthy controls. The correlation of molecular changes with psychopathology and cognitive performance of participants was evaluated. We observed downregulation of TCF4 and upregulation of MBP mRNA levels in SCZ cases, relative to controls in our study. DNA methylation status at the promoter region of TCF4 demonstrated an altered pattern in SCZ as well. Additionally, TCF4 mRNA levels were inversely correlated with PANSS and Stroop total errors and positively correlated with WAIS total score and working memory, consistent with previous studies by our group. In contrast, MBP mRNA level was significantly positively correlated with PANSS and Stroop total errors and inversely correlated with WAIS total score and working memory. These epigenetic and expression signatures can help to assemble a peripheral biomarker-based diagnostic panel for SCZ.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"738 - 750"},"PeriodicalIF":3.1,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527724","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":"Early Alterations of PACAP and VIP Expression in the Female Rat Brain Following Spinal Cord Injury","authors":"Sarah Thomas Broome,&nbsp;Mawj Mandwie,&nbsp;Catherine A. Gorrie,&nbsp;Giuseppe Musumeci,&nbsp;Rubina Marzagalli,&nbsp;Alessandro Castorina","doi":"10.1007/s12031-023-02151-w","DOIUrl":"10.1007/s12031-023-02151-w","url":null,"abstract":"<div><p>Previous evidence shows that rapid changes occur in the brain following spinal cord injury (SCI). Here, we interrogated the expression of the neuropeptides pituitary adenylyl cyclase-activating peptide (PACAP), vasoactive intestinal peptides (VIP), and their binding receptors in the rat brain 24 h following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy; half of the rats received a mild contusion injury at the level of the T10 vertebrate (SCI group); the other half underwent sham surgery (sham group). Twenty-four hours post-surgery, the hypothalamus, thalamus, amygdala, hippocampus (dorsal and ventral), prefrontal cortex, and periaqueductal gray were collected. PACAP, VIP, PAC1, VPAC1, and VPAC2 mRNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, PACAP expression was increased in the hypothalamus (104–141% vs sham) and amygdala (138–350%), but downregulated in the thalamus (35–95%) and periaqueductal gray (58–68%). VIP expression was increased only in the thalamus (175–385%), with a reduction in the amygdala (51–68%), hippocampus (40–75%), and periaqueductal gray (74–76%). The expression of the PAC1 receptor was the least disturbed by SCI, with decrease expression in the ventral hippocampus (63–68%) only. The expression levels of VPAC1 and VPAC2 receptors were globally reduced, with more prominent reductions of VPAC1 vs VPAC2 in the amygdala (21–70%) and ventral hippocampus (72–75%). In addition, VPAC1 downregulation also extended to the dorsal hippocampus (69–70%). These findings demonstrate that as early as 24 h post-SCI, there are region-specific disruptions of PACAP, VIP, and related receptor transcript and protein levels in supraspinal regions controlling higher cognitive functions.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"724 - 737"},"PeriodicalIF":3.1,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10116287","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":"BMP4, SGSH, and SLC11A2 are Predicted to Be Biomarkers of Aging Associated with Programmed Cell Death","authors":"Elif Kubat Oktem","doi":"10.1007/s12031-023-02148-5","DOIUrl":"10.1007/s12031-023-02148-5","url":null,"abstract":"<div><p>Most neurodegenerative diseases are exacerbated by aging, with symptoms often worsening over time. Programmed cell death (PCD) is a controlled cell suicide mechanism that is essential for the stability, growth, and homeostasis of organisms. Understanding the effects of aging at the level of systems biology could lead to new therapeutic approaches for a broad spectrum of neurodegenerative diseases. In the absence of comprehensive functional studies on the relationship between PCD and aging of the prefrontal cortex, this study provides prefrontal brain biomarkers of aging associated with PCD that could open the way for improved therapeutic techniques for age-related neurodegenerative diseases. To this end, publicly available transcriptome data were subjected to bioinformatic analyses such as differential gene expression, functional enrichment, and the weighted gene coexpression network analysis (WGCNA). The diagnostic utility of the biomarkers was tested using a logistic regression-based prediction model. Three genes, namely <i>BMP4</i>, <i>SGSH</i>, and <i>SLC11A2</i>, were found to be aging biomarkers associated with PCD. Finally, a multifactorial regulatory network with interacting proteins, transcription factors (TFs), competing endogenous RNAs (ceRNAs), and microRNAs (miRNAs) was constructed around these biomarkers. The elements of this multifactorial regulatory network were mainly enriched in BMP signaling. Further exploration of these three biomarkers and their regulatory elements would enable the development of 3PM (predictive, preventive, and personalized) medicine for the treatment of age-related neurodegenerative diseases.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"713 - 723"},"PeriodicalIF":3.1,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10131061","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":"Spreading of Tau Protein Does Not Depend on Aggregation Propensity","authors":"Sara Rodrigues,&nbsp;Marta Anglada-Huguet,&nbsp;Katja Hochgräfe,&nbsp;Senthilvelrajan Kaniyappan,&nbsp;Susanne Wegmann,&nbsp;Eva-Maria Mandelkow","doi":"10.1007/s12031-023-02143-w","DOIUrl":"10.1007/s12031-023-02143-w","url":null,"abstract":"<div><p>The stereotypical progression of Tau pathology during Alzheimer disease has been attributed to trans-neuronal spreading of misfolded Tau proteins, followed by prion-like templated aggregation of Tau. The nature of Tau and the cellular mechanisms of Tau spreading are still under debate. We hypothesized that Tau’s propensity for aggregation would correlate with its ability to spread across synapses and propagate pathology. To study the progressive propagation of Tau proteins in brain regions relevant for Alzheimer disease, we used mice expressing near-physiological levels of full-length human Tau protein carrying pro-aggregant (TauΔK280, Tau^ΔK) or anti-aggregant (TauΔK280-PP, Tau^ΔK−PP) mutations in the entorhinal cortex (EC). To enhance Tau expression in the EC, we performed EC injections of adeno-associated virus (AAV) particles encoding Tau^ΔK or Tau^ΔK−PP. The brains of injected and non-injected EC/Tau^ΔK and EC/Tau^ΔK−PP mice were studied by immunohistological and biochemical techniques to detect Tau propagation to dentate gyrus (DG) neurons and Tau-induced pathological changes. Pro- and anti-aggregant mice had comparable low transgene expression (~0.2 times endogenous mouse Tau). They accumulated human Tau at similar rates and only in expressing EC neurons, including their axonal projections of the perforant path and presynaptic terminals in the molecular layer of the DG. Pro-aggregant EC/Tau^ΔK mice showed misfolded Tau and synaptic protein alterations in EC neurons, not observed in anti-aggregant EC/Tau^ΔK−PP mice. Additional AAV-mediated expression of Tau^ΔK or Tau^ΔK−PP in EC/Tau^ΔK or EC/Tau^ΔK−PP mice, respectively, increased the human Tau expression to ~0.65 times endogenous mouse Tau, with comparable spreading of Tau^ΔK and Tau^ΔK−PP throughout the EC. There was a low level of transcellular propagation of Tau protein, without pathological phosphorylation or misfolding, as judged by diagnostic antibodies. Additionally, Tau^ΔK but not Tau^ΔK−PP expression induced hippocampal astrogliosis. Low levels of pro- or anti-aggregant full-length Tau show equivalent distributions in EC neurons, independent of their aggregation propensity. Increasing the expression via AAV induce local Tau misfolding in the EC neurons, synaptotoxicity, and astrogliosis and lead to a low level of detectable trans-neuronal spreading of Tau. This depends on its concentration in the EC, but, contrary to expectations, does not depend on Tau’s aggregation propensity/misfolding and does not lead to templated misfolding in recipient neurons.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"693 - 712"},"PeriodicalIF":3.1,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10040547","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":"Correction: Concurrent Assessment of Oxidative Stress and MT-ATP6 Gene Profiling to Facilitate Diagnosis of Autism Spectrum Disorder (ASD) in Tamil Nadu Population","authors":"Balachandar Vellingiri,&nbsp;Dhivya Venkatesan,&nbsp;Mahalaxmi Iyer,&nbsp;Gomathi Mohan,&nbsp;Padmavathi Krishnan,&nbsp;Krothapalli Sai Krishna,&nbsp;Sangeetha R,&nbsp;Arul Narayanasamy,&nbsp;Abilash Valsala Gopalakrishnan,&nbsp;Nachimuthu Senthil Kumar,&nbsp;Mohana Devi Subramaniam","doi":"10.1007/s12031-023-02137-8","DOIUrl":"10.1007/s12031-023-02137-8","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"485 - 485"},"PeriodicalIF":3.1,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4165705","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":"An Imbalance in the Pro/mature BDNF Ratio Occurs in Multiple Brain Regions During Normal Ageing in Wild-Type Mice","authors":"Shaun Cade,&nbsp;Xin-Fu Zhou,&nbsp;Larisa Bobrovskaya","doi":"10.1007/s12031-023-02131-0","DOIUrl":"10.1007/s12031-023-02131-0","url":null,"abstract":"<div><p>The early transition to Alzheimer’s disease is characterized by a period of accelerated brain atrophy that exceeds normal ageing. Identifying the molecular basis of this atrophy could facilitate the discovery of novel drug targets. The precursor of brain-derived neurotrophic factor, a well characterized neurotrophin, is increased in the hippocampus of aged rodents, while its mature isoform is relatively stable. This imbalance could increase the risk of Alzheimer’s disease by precipitating its pathological hallmarks. However, less is known about how relative levels of these isoforms change in middle-aged mice. In addition, the underlying mechanisms that might cause an imbalance are unknown. The main aim of this study was to determine how precursor brain-derived neurotrophic factor changes relative to its mature isoform with normal brain ageing in wild type mice. A secondary aim was to determine if signaling through the neurotrophin receptor, p75 influences this ratio. An increasing ratio was identified in several brain regions, except the hippocampus, suggesting a neurotrophic imbalance occurs as early as middle age. Some changes in receptors that mediate the isoforms effects were also identified, but these did not correspond with trends in the isoforms. Relative amounts of precursor brain-derived neurotrophic factor were mostly unchanged in mutant p75 mice. The lack of changes suggested that signaling through the receptor had no influence on the ratio.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"469 - 484"},"PeriodicalIF":3.1,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-023-02131-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4579517","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":"H2S Alleviates Neuropathic Pain in Mice by Nrf2 Signaling Pathway Activation","authors":"Jun Wang,&nbsp;Nan Zhang,&nbsp;Hong-Zheng Liu,&nbsp;Jin-Liang Wang,&nbsp;Yong-Bo Zhang,&nbsp;Dong-Dong Su,&nbsp;Jun Miao","doi":"10.1007/s12031-023-02134-x","DOIUrl":"10.1007/s12031-023-02134-x","url":null,"abstract":"<div><p>Neuropathic pain is a chronic pain caused by direct damage to the peripheral or central nervous system, characterized by hyperalgesia, allodynia, and spontaneous pain. Hydrogen sulfide (H₂S) therapy has been applied for neuropathic pain treatment, although the underlying mechanisms remain unknown. In this study, we sought to ascertain whether H₂S therapy could alleviate neuropathic pain in a model of chronic constriction injury (CCI) and, if so, the potential mechanism. A CCI model was established in mice through a spinal nerve ligation method. Intrathecal injection of NaHS was used to treat CCI model mice. The thermal paw withdrawal latency (TPWL) and mechanical paw withdrawal threshold (MPWT) were used for pain threshold evaluation in mice. A series of experiments including immunofluorescence, enzyme-linked immunosorbent assay, electrophysiological test, mitochondrial DNA (mtDNA) quantification, measurement of ATP content, demethylase activity, and western blot were performed to investigate the specific mechanism of H2S treatment in neuropathic pain. Mice with CCI exposure exhibited a decrease in MPWT and TPWL, an increase in IL-1β and TNF-α expressions, elevated eEPSP amplitude, an upregulation of mtDNA, and a reduction in ATP production, whereas H₂S treatment significantly reversed these changes. Furthermore, CCI exposure induced a remarkable increase in vGlut2- and c-fos-positive as well as vGlut2- and Nrf2-positive cells, an increase in Nrf2 located in the nucleus, and an upregulation of H3K4 methylation, and H₂S treatment further enhanced these changes. In addition, ML385, a selective Nrf2 inhibitor, reversed the neuroprotective effects of H₂S. H₂S treatment mitigates CCI-induced neuropathic pain in mice. This protective mechanism is possibly linked to the activation of the Nrf2 signaling pathway in vGlut2-positive cells.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 6","pages":"456 - 468"},"PeriodicalIF":3.1,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4389742","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}