Molecular Brain最新文献_第5页

Absence of ATG9A and synaptophysin demixing on Rab5 mutation-induced giant endosomes. Rab5突变诱导的巨型内体上缺乏ATG9A和突触素脱混。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-09-02 DOI: 10.1186/s13041-024-01132-3

Jiyoung Choi, Yumei Wu, Daehun Park

引用次数: 0

Electroacupuncture reduces inflammatory damage following cerebral ischemia-reperfusion by enhancing ABCA1-mediated efferocytosis in M2 microglia. 电针通过提高 M2 小胶质细胞 ABCA1 介导的排泄功能减轻脑缺血再灌注后的炎症损伤。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-09-02 DOI: 10.1186/s13041-024-01135-0

Yu-Sha Liao, Tie-Chun Zhang, Yu-Qi Tang, Pei Yu, Ya-Ning Liu, Jing Yuan, Ling Zhao

{"title":"Electroacupuncture reduces inflammatory damage following cerebral ischemia-reperfusion by enhancing ABCA1-mediated efferocytosis in M2 microglia.","authors":"Yu-Sha Liao, Tie-Chun Zhang, Yu-Qi Tang, Pei Yu, Ya-Ning Liu, Jing Yuan, Ling Zhao","doi":"10.1186/s13041-024-01135-0","DOIUrl":"10.1186/s13041-024-01135-0","url":null,"abstract":"Ischemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"61"},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Felodipine attenuates neuroinflammatory responses and tau hyperphosphorylation through JNK/P38 signaling in tau-overexpressing AD mice. 非洛地平通过JNK/P38信号转导减轻tau过表达AD小鼠的神经炎症反应和tau高磷酸化。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-09-02 DOI: 10.1186/s13041-024-01137-y

Jeong-Woo Hwang, Jeongha Kim, Jin-Hee Park, Jinhan Nam, Ji-Yeong Jang, Aran Jo, Hyun-Ju Lee, Hyang-Sook Hoe

{"title":"Felodipine attenuates neuroinflammatory responses and tau hyperphosphorylation through JNK/P38 signaling in tau-overexpressing AD mice.","authors":"Jeong-Woo Hwang, Jeongha Kim, Jin-Hee Park, Jinhan Nam, Ji-Yeong Jang, Aran Jo, Hyun-Ju Lee, Hyang-Sook Hoe","doi":"10.1186/s13041-024-01137-y","DOIUrl":"10.1186/s13041-024-01137-y","url":null,"abstract":"We previously demonstrated that felodipine, an L-type calcium channel blocker, inhibits LPS-mediated neuroinflammatory responses in BV2 microglial cells and wild-type mice. However, the effects of felodipine on tau pathology, a hallmark of Alzheimer's disease (AD), have not been explored yet. Therefore, in the present study, we determined whether felodipine affects neuroinflammation and tau hyperphosphorylation in 3-month-old P301S transgenic mice (PS19), an early phase AD mice model for tauopathy. Felodipine administration decreased tauopathy-mediated microglial activation and NLRP3 expression in PS19 mice but had no effect on tauopathy-associated astrogliosis. In addition, felodipine treatment significantly reduced tau hyperphosphorylation at S202/Thr205 and Thr212/Ser214 residues via inhibiting JNK/P38 signaling in PS19 mice. Collectively, our results suggest that felodipine significantly ameliorates tau hyper-phosphorylation and tauopathy-associated neuroinflammatory responses in AD mice model for tauopathy and could be a novel therapeutic agent for AD.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"62"},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Running-induced neurogenesis reduces CA1 perineuronal net density without substantial temporal delay. 奔跑诱导的神经发生降低了CA1神经元周围的净密度，但没有明显的时间延迟。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-09-02 DOI: 10.1186/s13041-024-01138-x

Dylan J Terstege, Duneesha Goonetilleke, Cindy K Barha, Jonathan R Epp

{"title":"Running-induced neurogenesis reduces CA1 perineuronal net density without substantial temporal delay.","authors":"Dylan J Terstege, Duneesha Goonetilleke, Cindy K Barha, Jonathan R Epp","doi":"10.1186/s13041-024-01138-x","DOIUrl":"10.1186/s13041-024-01138-x","url":null,"abstract":"Aerobic exercise has many effects on brain function, particularly at the hippocampus. Exercise has been shown to increase the rate of adult neurogenesis within the dentate gyrus and decrease the density of perineuronal nets in area CA1. The relationship between the rate of neurogenesis and the density of perineuronal nets in CA1 is robust; however, these studies only ever examined these effects across longer time scales, with running manipulations of 4 weeks or longer. With such long periods of manipulation, the precise temporal nature of the relationship between running-induced neurogenesis and reduced perineuronal net density in CA1 is unknown. Here, we provided male and female mice with home cage access to running wheels for 0, 1, 2, or 4 weeks and quantified hippocampal neurogenesis and CA1 perineuronal net density. In doing so, we observed a 2-week delay period prior to the increase in neurogenesis, which coincided with the same delay prior to decreased CA1 perineuronal net density. These results highlight the closely linked temporal relationship between running-induced neurogenesis and decreased perineuronal net expression in CA1.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"64"},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Altered brain connectivity in mild cognitive impairment is linked to elevated tau and phosphorylated tau, but not to GAP-43 and Amyloid-β measurements: a resting-state fMRI study. 轻度认知障碍患者大脑连通性的改变与 tau 和磷酸化 tau 的升高有关，但与 GAP-43 和淀粉样蛋白-β 的测量无关：一项静息态 fMRI 研究。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-08-30 DOI: 10.1186/s13041-024-01136-z

Mohammad Sadeghi, Ali Azargoonjahromi, Hamide Nasiri, Arash Yaghoobi, Maryam Sadeghi, Seyedeh Saeideh Chavoshi, Shilan Baghaeikia, Nastaran Mahzari, Arina Valipour, Romina Razeghi Oskouei, Farshad Shahkarami, Fatemeh Amiri, Mahsa Mayeli

{"title":"Altered brain connectivity in mild cognitive impairment is linked to elevated tau and phosphorylated tau, but not to GAP-43 and Amyloid-β measurements: a resting-state fMRI study.","authors":"Mohammad Sadeghi, Ali Azargoonjahromi, Hamide Nasiri, Arash Yaghoobi, Maryam Sadeghi, Seyedeh Saeideh Chavoshi, Shilan Baghaeikia, Nastaran Mahzari, Arina Valipour, Romina Razeghi Oskouei, Farshad Shahkarami, Fatemeh Amiri, Mahsa Mayeli","doi":"10.1186/s13041-024-01136-z","DOIUrl":"10.1186/s13041-024-01136-z","url":null,"abstract":"Mild Cognitive Impairment (MCI) is a neurological condition characterized by a noticeable decline in cognitive abilities that falls between normal aging and dementia. Along with some biomarkers like GAP-43, Aβ, tau, and P-tau, brain activity and connectivity are ascribed to MCI; however, the link between brain connectivity changes and such biomarkers in MCI is still being investigated. This study explores the relationship between biomarkers like GAP-43, Aβ, tau, and P-tau, and brain connectivity. We enrolled 25 Participants with normal cognitive function and 23 patients with MCI. Levels of GAP-43, Aβ1-42, t-tau, and p-tau181p in the CSF were measured, and functional connectivity measures including ROI-to-voxel (RV) correlations and the DMN RV-ratio were extracted from the resting-state fMRI data. P-values below 0.05 were considered significant. The results showed that in CN individuals, higher connectivity within the both anterior default mode network (aDMN) and posterior DMN (pDMN) was associated with higher levels of the biomarker GAP-43. In contrast, MCI individuals showed significant negative correlations between DMN connectivity and levels of tau and P-tau. Notably, no significant correlations were found between Aβ levels and connectivity measures in either group. These findings suggest that elevated levels of GAP-43 indicate increased functional connectivity in aDMN and pDMN. Conversely, elevated levels of tau and p-tau can disrupt connectivity through various mechanisms. Thus, the accumulation of tau and p-tau can lead to impaired neuronal connectivity, contributing to cognitive decline.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"60"},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocyte-derived dominance winning reverses chronic stress-induced depressive behaviors. 源自星形胶质细胞的优势胜势可逆转慢性压力诱发的抑郁行为

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-08-27 DOI: 10.1186/s13041-024-01134-1

Kyungchul Noh, Junyoung Oh, Woo-Hyun Cho, Minkyu Hwang, Sung Joong Lee

{"title":"Astrocyte-derived dominance winning reverses chronic stress-induced depressive behaviors.","authors":"Kyungchul Noh, Junyoung Oh, Woo-Hyun Cho, Minkyu Hwang, Sung Joong Lee","doi":"10.1186/s13041-024-01134-1","DOIUrl":"10.1186/s13041-024-01134-1","url":null,"abstract":"Individuals with low social status are at heightened risk of major depressive disorder (MDD), and MDD also influences social status. While the interrelationship between MDD and social status is well-defined, the behavioral causality between these two phenotypes remains unexplored. Here, we investigated the behavioral relationships between depressive and dominance behaviors in male mice exposed to chronic restraint stress and the role of medial prefrontal cortex (mPFC) astrocytes in these behaviors. Chronic restraint stress induced both depressive and submissive behaviors. Chemogenetic mPFC astrocyte activation significantly enhanced dominance in chronic stress-induced submissive mice by increasing the persistence of defensive behavior, although it did not affect depressive behaviors. Notably, repetitive winning experiences following mPFC astrocyte stimulation exerted anti-depressive effects in chronic restraint stress-induced depressive mice. These data indicate that mPFC astrocyte-derived winning experience renders anti-depressive effects, and may offer a new strategy for treating depression caused by low status in social hierarchies by targeting mPFC astrocytes.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"59"},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protocadherin 19 regulates axon guidance in the developing Xenopus retinotectal pathway. 原粘连蛋白19调节发育中的章鱼视网膜通路的轴突导向。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-08-22 DOI: 10.1186/s13041-024-01130-5

Jane Jung, Jugeon Park, Sihyeon Park, Chul Hoon Kim, Hosung Jung

引用次数: 0

Comprehensive identification of ubiquitin-like 3 (UBL3)-interacting proteins in the mouse brain. 全面鉴定小鼠大脑中与泛素样 3 (UBL3) 相互作用的蛋白

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-08-15 DOI: 10.1186/s13041-024-01131-4

Hiroshi Ageta, Tomoki Nishioka, Hisateru Yamaguchi, Kunihiro Tsuchida, Natsumi Ageta-Ishihara

{"title":"Comprehensive identification of ubiquitin-like 3 (UBL3)-interacting proteins in the mouse brain.","authors":"Hiroshi Ageta, Tomoki Nishioka, Hisateru Yamaguchi, Kunihiro Tsuchida, Natsumi Ageta-Ishihara","doi":"10.1186/s13041-024-01131-4","DOIUrl":"10.1186/s13041-024-01131-4","url":null,"abstract":"Discovery of novel post-translational modifications provides new insights into changes in protein function, localization, and stability. They are also key elements in understanding disease mechanisms and developing therapeutic strategies. We have previously reported that ubiquitin-like 3 (UBL3) serves as a novel post-translational modifier that is highly expressed in the cerebral cortex and hippocampus, in addition to various other organs, and that 60% of proteins contained in small extracellular vesicles (sEVs), including exosomes, are influenced by UBL3. In this study, we generated transgenic mice expressing biotinylated UBL3 in the forebrain under control of the alpha-CaMKII promoter (Ubl3Tg/+). Western blot analysis revealed that the expression of UBL3 in the cerebral cortex and hippocampus was 6- to 7-fold higher than that in the cerebellum. Therefore, we performed immunoprecipitation of protein extracts from the cerebral cortex of Ubl3+/+ and Ubl3Tg/+ mice using avidin beads to comprehensively discover UBL3 interacting proteins, identifying 35 new UBL3 interacting proteins. Nine proteins were annotated as extracellular exosomes. Gene Ontology (GO) analysis suggested a new relationship between sEVs and RNA metabolism in neurodegenerative diseases. We confirmed the association of endogenous UBL3 with the RNA-binding proteins FUS and HPRT1-both listed in the Neurodegenerative Diseases Variation Database (NDDVD)-and with LYPLA1, which is involved in Huntington's disease, using immunoprecipitation (IP)-western blotting analysis. These UBL3 interacting proteins will accelerate the continued elucidation of sEV research about proteins regulated by novel post-translational modifications by UBL3 in the brain.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"57"},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson's disease. 少突胶质细胞和前体细胞的转录组变化与帕金森病的临床结果有关。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-08-13 DOI: 10.1186/s13041-024-01128-z

Mohammad Dehestani, Velina Kozareva, Cornelis Blauwendraat, Ernest Fraenkel, Thomas Gasser, Vikas Bansal

{"title":"Transcriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson's disease.","authors":"Mohammad Dehestani, Velina Kozareva, Cornelis Blauwendraat, Ernest Fraenkel, Thomas Gasser, Vikas Bansal","doi":"10.1186/s13041-024-01128-z","DOIUrl":"10.1186/s13041-024-01128-z","url":null,"abstract":"Several prior studies have proposed the involvement of various brain regions and cell types in Parkinson's disease (PD) pathology. Here, we performed snRNA-seq on the prefrontal cortex and anterior cingulate regions from a small cohort of post-mortem control and PD brain tissue. We found a significant association of oligodendrocytes (ODCs) and oligodendrocyte precursor cells (OPCs) with PD-linked risk loci and report several dysregulated genes and pathways, including regulation of tau-protein kinase activity, regulation of inclusion body assembly and protein processing involved in protein targeting to mitochondria. In an independent PD cohort with clinical measures (681 cases and 549 controls), polygenic risk scores derived from the dysregulated genes significantly predicted Montreal Cognitive Assessment (MoCA)-, and Beck Depression Inventory-II (BDI-II)-scores but not motor impairment (UPDRS-III). We extended our analysis of clinical outcome prediction by incorporating differentially expressed genes from three separate datasets that were previously published by different laboratories. In the first dataset from the anterior cingulate cortex, we identified an association between ODCs and BDI-II. In the second dataset obtained from the substantia nigra (SN), OPCs displayed an association with UPDRS-III. In the third dataset from the SN region, a distinct subtype of OPCs, labeled OPC_ADM, exhibited an association with UPDRS-III. Intriguingly, the OPC_ADM cluster also demonstrated a significant increase in PD samples. These results suggest that by expanding our focus to glial cells, we can uncover region-specific molecular pathways associated with PD symptoms.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"56"},"PeriodicalIF":3.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Database-assisted screening of autism spectrum disorder related gene set. 数据库辅助筛选自闭症谱系障碍相关基因组。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-08-09 DOI: 10.1186/s13041-024-01127-0

Éva Kereszturi

{"title":"Database-assisted screening of autism spectrum disorder related gene set.","authors":"Éva Kereszturi","doi":"10.1186/s13041-024-01127-0","DOIUrl":"10.1186/s13041-024-01127-0","url":null,"abstract":"Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication difficulties, along with repetitive behaviors. While genetic factors play a significant role in ASD, the precise genetic landscape remains complex and not fully understood, particularly in non-syndromic cases. The study performed an in silico comparison of three genetic databases. ClinVar, SFARI Gene, and AutDB were utilized to identify relevant gene subset and genetic variations associated with non-syndromic ASD. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analysis were conducted to elucidate the biological significance of the identified genes. The integrity of ASD-related gene subset and the distribution of their variations were statistically assessed. A subset of twenty overlapping genes potentially specific for non-syndromic ASD was identified. GSEA revealed enrichment of biological processes related to neuronal development and differentiation, synaptic function, and social skills, highlighting their importance in ASD pathogenesis. PPI network analysis demonstrated functional relationships among the identified genes. Analysis of genetic variations showed predominance of rare variants and database-specific distribution patterns. The results provide valuable insights into the genetic landscape of ASD and outline the genes and biological processes involved in the condition, while taking into account that the study relied exclusively on in silico analyses, which may be subject to biases inherent to database methodologies. Further research incorporating multi-omics data and experimental validation is warranted to enhance our understanding of non-syndromic ASD genetics and facilitate the development of targeted research, interventions and therapies.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"55"},"PeriodicalIF":3.3,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0