Molecular Brain最新文献_第7页

Single-molecule imaging of Tau reveals how phosphorylation affects its movement and confinement in living cells. Tau 的单分子成像揭示了磷酸化如何影响其在活细胞中的移动和封闭。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-02-12 DOI: 10.1186/s13041-024-01078-6

Pranesh Padmanabhan, Andrew Kneynsberg, Esteban Cruz, Adam Briner, Jürgen Götz

{"title":"Single-molecule imaging of Tau reveals how phosphorylation affects its movement and confinement in living cells.","authors":"Pranesh Padmanabhan, Andrew Kneynsberg, Esteban Cruz, Adam Briner, Jürgen Götz","doi":"10.1186/s13041-024-01078-6","DOIUrl":"10.1186/s13041-024-01078-6","url":null,"abstract":"Tau is a microtubule-associated protein that is regulated by post-translational modifications. The most studied of these modifications is phosphorylation, which affects Tau's aggregation and loss- and gain-of-functions, including the interaction with microtubules, in Alzheimer's disease and primary tauopathies. However, little is known about how Tau's phosphorylation state affects its dynamics and organisation at the single-molecule level. Here, using quantitative single-molecule localisation microscopy, we examined how mimicking or abrogating phosphorylation at 14 disease-associated serine and threonine residues through mutagenesis influences the behaviour of Tau in live Neuro-2a cells. We observed that both pseudohyperphosphorylated Tau (TauE14) and phosphorylation-deficient Tau (TauA14) exhibit a heterogeneous mobility pattern near the plasma membrane. Notably, we found that the mobility of TauE14 molecules was higher than wild-type Tau molecules, while TauA14 molecules displayed lower mobility. Moreover, TauA14 was organised in a filament-like structure resembling cytoskeletal filaments, within which TauA14 exhibited spatial and kinetic heterogeneity. Our study provides a direct visualisation of how the phosphorylation state of Tau affects its spatial and temporal organisation, presumably reflecting the phosphorylation-dependent changes in the interactions between Tau and its partners. We suggest that alterations in Tau dynamics resulting from aberrant changes in phosphorylation could be a critical step in its pathological dysregulation.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723337","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

Correction: The deficiency of Maged1 attenuates Parkinson's disease progression in mice. 更正：缺乏 Maged1 可减轻小鼠帕金森病的进展。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-02-09 DOI: 10.1186/s13041-023-01075-1

Jie Wang, Sheng-Ye Xu, Zhi-Yuan Ye, Zhou-Na Sun, Jia-Qi Zhang, Cui Qi, Rui Liu, Xiang Gao, Chuan He, Wei-Yan You, Jun Gao

引用次数: 0

Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice. 小鼠内侧内皮层外层的 Vb 神经元可投射到海马齿状回。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-02-05 DOI: 10.1186/s13041-024-01079-5

Naoki Yamamoto, Jun Yokose, Kritika Ramesh, Takashi Kitamura, Sachie K Ogawa

{"title":"Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice.","authors":"Naoki Yamamoto, Jun Yokose, Kritika Ramesh, Takashi Kitamura, Sachie K Ogawa","doi":"10.1186/s13041-024-01079-5","DOIUrl":"10.1186/s13041-024-01079-5","url":null,"abstract":"Entorhinal cortical (EC)-hippocampal (HPC) circuits are crucial for learning and memory. Although it was traditionally believed that superficial layers (II/III) of the EC mainly project to the HPC and deep layers (V/VI) receive input from the HPC, recent studies have highlighted the significant projections from layers Va and VI of the EC into the HPC. However, it still remains unknown whether Vb neurons in the EC provide projections to the hippocampus. In this study, using a molecular marker for Vb and retrograde tracers, we identified that the outer layer of Vb neurons in the medial EC (MEC) directly project to both dorsal and ventral hippocampal dentate gyrus (DG), with a significant preference for the ventral DG. In contrast to the distribution of DG-projecting Vb cells, anterior thalamus-projecting Vb cells are distributed through the outer to the inner layer of Vb. Furthermore, dual tracer injections revealed that DG-projecting Vb cells and anterior thalamus-projecting Vb cells are distinct populations. These results suggest that the roles of MEC Vb neurons are not merely limited to the formation of EC-HPC loop circuits, but rather contribute to multiple neural processes for learning and memory.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692367","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

The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology. 多发性硬化症的脑细胞因子乐团：从神经炎症到突触病理学。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-01-23 DOI: 10.1186/s13041-024-01077-7

Roberta Amoriello, Christian Memo, Laura Ballerini, Clara Ballerini

{"title":"The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology.","authors":"Roberta Amoriello, Christian Memo, Laura Ballerini, Clara Ballerini","doi":"10.1186/s13041-024-01077-7","DOIUrl":"10.1186/s13041-024-01077-7","url":null,"abstract":"The central nervous system (CNS) is finely protected by the blood-brain barrier (BBB). Immune soluble factors such as cytokines (CKs) are normally produced in the CNS, contributing to physiological immunosurveillance and homeostatic synaptic scaling. CKs are peptide, pleiotropic molecules involved in a broad range of cellular functions, with a pivotal role in resolving the inflammation and promoting tissue healing. However, pro-inflammatory CKs can exert a detrimental effect in pathological conditions, spreading the damage. In the inflamed CNS, CKs recruit immune cells, stimulate the local production of other inflammatory mediators, and promote synaptic dysfunction. Our understanding of neuroinflammation in humans owes much to the study of multiple sclerosis (MS), the most common autoimmune and demyelinating disease, in which autoreactive T cells migrate from the periphery to the CNS after the encounter with a still unknown antigen. CNS-infiltrating T cells produce pro-inflammatory CKs that aggravate local demyelination and neurodegeneration. This review aims to recapitulate the state of the art about CKs role in the healthy and inflamed CNS, with focus on recent advances bridging the study of adaptive immune system and neurophysiology.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542185","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

Long-term inhibition of ODC1 in APP/PS1 mice rescues amyloid pathology and switches astrocytes from a reactive to active state. 在APP/PS1小鼠体内长期抑制ODC1可挽救淀粉样病理，并使星形胶质细胞从反应状态转为活跃状态。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-01-12 DOI: 10.1186/s13041-024-01076-8

Mridula Bhalla, C Justin Lee

{"title":"Long-term inhibition of ODC1 in APP/PS1 mice rescues amyloid pathology and switches astrocytes from a reactive to active state.","authors":"Mridula Bhalla, C Justin Lee","doi":"10.1186/s13041-024-01076-8","DOIUrl":"10.1186/s13041-024-01076-8","url":null,"abstract":"Alzheimer's disease (AD) is characterized by the loss of memory due to aggregation of misphosphorylated tau and amyloid beta (Aβ) plaques in the brain, elevated release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and reactive oxygen species from astrocytes, and subsequent neurodegeneration. Recently, it was found that enzyme Ornithine Decarboxylase 1 (ODC1) acts as a bridge between the astrocytic urea cycle and the putrescine-to-GABA conversion pathway in the brain of AD mouse models as well as human patients. In this study, we show that the long-term knockdown of astrocytic Odc1 in APP/PS1 animals was sufficient to completely clear Aβ plaques in the hippocampus while simultaneously switching the astrocytes from a detrimental reactive state to a regenerative active state, characterized by proBDNF expression. Our experiments also reveal an effect of astrocytic ODC1 inhibition on the expression of genes involved in synapse pruning and organization, histone modification, apoptotic signaling and protein processing. These genes are previously known to be associated with astrocytic activation and together create a neuroregeneration-supportive environment in the brain. By inhibiting ODC1 for a long period of 3 months in AD mice, we demonstrate that the beneficial amyloid-clearing process of astrocytes can be completely segregated from the systemically harmful astrocytic response to insult. Our study reports an almost complete clearance of Aβ plaques by controlling an endogenous degradation process, which also modifies the astrocytic state to create a regeneration-supportive environment in the brain. These findings present the potential of modulating astrocytic clearance of Aβ as a powerful therapeutic strategy against AD.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432669","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

Neurexin-1-dependent circuit activity is required for the maintenance of photoreceptor subtype identity in Drosophila 果蝇感光器亚型特征的维持需要依赖 Neurexin-1 的回路活动

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-01-02 DOI: 10.1186/s13041-023-01073-3

Gabrielle Lim-Kian-Siang, Arianna R. Izawa-Ishiguro, Yong Rao

{"title":"Neurexin-1-dependent circuit activity is required for the maintenance of photoreceptor subtype identity in Drosophila","authors":"Gabrielle Lim-Kian-Siang, Arianna R. Izawa-Ishiguro, Yong Rao","doi":"10.1186/s13041-023-01073-3","DOIUrl":"https://doi.org/10.1186/s13041-023-01073-3","url":null,"abstract":"In the human and Drosophila color vision system, each photoreceptor neuron (cone cell in humans and R7/R8 photoreceptor cell in Drosophila) makes a stochastic decision to express a single photopigment of the same family with the exclusion of the others. While recent studies have begun to reveal the mechanisms that specify the generation of cone subtypes during development in mammals, nothing is known about how the mosaic of mutually exclusive cone subtypes is maintained in the mammalian retina. In Drosophila, recent work has led to the identification of several intrinsic factors that maintain the identity of R8 photoreceptor subtypes in adults. Whether and how extrinsic mechanisms are involved, however, remain unknown. In this study, we present evidence that supports that the Drosophila transsynaptic adhesion molecule Neurexin 1 (Dnrx-1) is required non-cell autonomously in R8p subtypes for the maintenance of R8y subtype identity. Silencing the activity of R8p subtypes caused a phenotype identical to that in dnrx-1 mutants. These results support a novel role for Nrx-1-dependent circuit activity in mediating the communication between R8 photoreceptor subtypes for maintaining the subtype identity in the retina.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139079650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of synaptic transmission through O-GlcNAcylation 通过 O-GlcNAcylation 调节突触传递

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-01-02 DOI: 10.1186/s13041-023-01072-4

Seunghyo Han, Jun-Nyeong Kim, Chan Ho Park, Jin-Seok Byun, Do-Yeon Kim, Hyoung-Gon Ko

引用次数: 0

Exploring Piezo1, Piezo2, and TMEM150C in human brain tissues and their correlation with brain biomechanical characteristics 探索人脑组织中的 Piezo1、Piezo2 和 TMEM150C 及其与脑生物力学特征的相关性

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-12-20 DOI: 10.1186/s13041-023-01071-5

Arjun Raha, Yuning Wu, Lily Zhong, Jatheeshan Raveenthiran, Minji Hong, Aftab Taiyab, Li Wang, Bill Wang, Fei Geng

{"title":"Exploring Piezo1, Piezo2, and TMEM150C in human brain tissues and their correlation with brain biomechanical characteristics","authors":"Arjun Raha, Yuning Wu, Lily Zhong, Jatheeshan Raveenthiran, Minji Hong, Aftab Taiyab, Li Wang, Bill Wang, Fei Geng","doi":"10.1186/s13041-023-01071-5","DOIUrl":"https://doi.org/10.1186/s13041-023-01071-5","url":null,"abstract":"Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet the underlying mechanistic model of signaling pathways in brain mechanotransduction remains enigmatic. To bridge this gap, we introduced an in situ multi-scale platform, through which we delineate comprehensive brain biomechanical traits in white matter (WM), grey-white matter junctions (GW junction), and the pons across human brain tissue from four distinct donors. We investigate the three-dimensional expression patterns of Piezo1, Piezo2, and TMEM150C, while also examining their associated histological features and mechanotransduction signaling networks, particularly focusing on the YAP/β-catenin axis. Our results showed that the biomechanical characteristics (including stiffness, spring term, and equilibrium stress) associated with Piezo1 vary depending on the specific region. Moving beyond Piezo1, our result demonstrated the significant positive correlations between Piezo2 expression and stiffness in the WM. Meanwhile, the expression of Piezo2 and TMEM150C was shown to be correlated to viscoelastic properties in the pons and WM. Given the heterogeneity of brain tissue, we investigated the three-dimensional expression of Piezo1, Piezo2, and TMEM150C. Our results suggested that three mechanosensitive proteins remained consistent across different vertical planes within the tissue sections. Our findings not only establish Piezo1, Piezo2, and TMEM150C as pivotal mechanosensors that regulate the region-specific mechanotransduction activities but also unveil the paradigm connecting brain mechanical properties and mechanotransduction activities and the variations between individuals.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138816505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathophysiology of ion channels in amyotrophic lateral sclerosis 肌萎缩性脊髓侧索硬化症的离子通道病理生理学

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-12-15 DOI: 10.1186/s13041-023-01070-6

Robin N. Stringer, Norbert Weiss

引用次数: 0

Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain 脊髓星形胶质细胞通过突触周围星形胶质细胞过程在病理性疼痛中的作用

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-12-13 DOI: 10.1186/s13041-023-01069-z

Hyoung-Gon Ko, Heejung Chun, Seunghyo Han, Bong-Kiun Kaang

{"title":"Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain","authors":"Hyoung-Gon Ko, Heejung Chun, Seunghyo Han, Bong-Kiun Kaang","doi":"10.1186/s13041-023-01069-z","DOIUrl":"https://doi.org/10.1186/s13041-023-01069-z","url":null,"abstract":"Pathological pain is caused by abnormal activity in the neural circuit that transmits nociceptive stimuli. Beyond homeostatic functions, astrocytes actively participate in regulating synaptic transmission as members of tripartite synapses. The perisynaptic astrocytic process (PAP) is the key structure that allows astrocytes to play these roles and not only physically supports synapse formation through cell adhesion molecules (CAMs) but also regulates the efficiency of chemical signaling. Accumulating evidence has revealed that spinal astrocytes are involved in pathological pain by modulating the efficacy of neurotransmitters such as glutamate and GABA through transporters located in the PAP and by directly regulating synaptic transmission through various gliotransmitters. Although various CAMs contribute to pathological pain, insufficient evidence is available as to whether astrocytic CAMs also have this role. Therefore, more in-depth research is needed on how pathological pain is induced and maintained by astrocytes, especially in the PAP surrounding the synapse, and this will subsequently increase our understanding and treatment of pathological pain.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138581143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0