Molecular Brain最新文献_第10页

TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway. TREM2 通过调节 P38 MAPK 信号通路改善自闭症谱系障碍中的小胶质细胞功能和突触发育。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-02-26 DOI: 10.1186/s13041-024-01081-x

Yi Tian, Xiao Xiao, Weiliang Liu, Shanqing Cheng, Na Qian, Ling Wang, Yang Liu, Rong Ai, Xiaoping Zhu

{"title":"TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway.","authors":"Yi Tian, Xiao Xiao, Weiliang Liu, Shanqing Cheng, Na Qian, Ling Wang, Yang Liu, Rong Ai, Xiaoping Zhu","doi":"10.1186/s13041-024-01081-x","DOIUrl":"10.1186/s13041-024-01081-x","url":null,"abstract":"Background: Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders, but the precise underlying pathogenesis remains elusive. This study aim to explore the potential mechanism of TREM2 in regulating microglia function in ASD.Materials and methods: The offspring rat model of ASD was established through prenatal exposure to valproic acid (VPA), and the behavioral symptoms of the ASD model were observed. On postnatal day (PND) 7 and PND 28, the effects of prenatally exposure to VPA on synaptic development and microglia phenotype of offspring rats were observed. Primary microglia were cultured in vitro. Lentivirus and adenovirus were utilized to interfere with TREM2 and overexpress TREM2.Results: Prenatally VPA exposure induced offspring rats to show typical ASD core symptoms, which led to abnormal expression of synapse-related proteins in the prefrontal cortex of offspring rats, changed the phenotype of microglia in offspring rats, promoted the polarization of microglia to pro-inflammatory type, and increased inflammatory response. The experimental results in vitro showed that overexpression of TREM2 could increase the expression of Gephyrin, decrease the content of CD86 protein and increase the content of CD206 protein. In addition, after the expression of TREM2 was interfered, the content of p-P38 MAPK protein increased and the content of p-ELK-1 protein decreased.Conclusion: The protective influence of TREM2 on the VPA-induced ASD model is attributed to its inhibition of the P38 MAPK pathway, this protective effect may be achieved by promoting the polarization of microglia to anti-inflammatory phenotype and improving the neuronal synaptic development.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"12"},"PeriodicalIF":3.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972740","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

Selective enhancement of fear extinction by inhibiting neuronal adenylyl cyclase 1 (AC1) in aged mice. 抑制神经元腺苷酸环化酶 1（AC1）可选择性地增强老年小鼠的恐惧消退能力。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-02-22 DOI: 10.1186/s13041-024-01083-9

Wantong Shi, Qi-Yu Chen, Yujie Ma, Jinjin Wan, Xu-Hui Li, Min Zhuo

{"title":"Selective enhancement of fear extinction by inhibiting neuronal adenylyl cyclase 1 (AC1) in aged mice.","authors":"Wantong Shi, Qi-Yu Chen, Yujie Ma, Jinjin Wan, Xu-Hui Li, Min Zhuo","doi":"10.1186/s13041-024-01083-9","DOIUrl":"10.1186/s13041-024-01083-9","url":null,"abstract":"Adenylyl cyclase 1 (AC1) is a selective subtype of ACs, which is selectively expressed in neurons. The activation of AC1 is activity-dependent, and AC1 plays an important role in cortical excitation that contributes to chronic pain and related emotional disorders. Previous studies have reported that human-used NB001 (hNB001, a selective AC1 inhibitor) produced analgesic effects in different animal models of chronic pain. However, the potential effects of hNB001 on learning and memory have been less investigated. In the present study, we found that hNB001 affected neither the induction nor the expression of trace fear, but selectively enhanced the relearning ability during the extinction in aged mice. By contrast, the same application of hNB001 did not affect recent, remote auditory fear memory, or remote fear extinction in either adult or aged mice. Furthermore, a single or consecutive 30-day oral administration of hNB001 did not affect acute nociceptive response, motor function, or anxiety-like behavior in either adult or aged mice. Our results are consistent with previous findings that inhibition of AC1 did not affect general sensory, emotional, and motor functions in adult mice, and provide strong evidence that inhibiting the activity of AC1 may be beneficial for certain forms of learning and memory in aged mice.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"11"},"PeriodicalIF":3.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10885434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932060","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

A simple and reliable method for claustrum localization across age in mice. 一种简单可靠的小鼠跨年龄耳廓定位方法。

IF 3.3 3区医学

Molecular Brain Pub Date : 2024-02-17 DOI: 10.1186/s13041-024-01082-w

Tarek Shaker, Gwyneth J Dagpa, Vanessa Cattaud, Brian A Marriott, Mariam Sultan, Mohammed Almokdad, Jesse Jackson

{"title":"A simple and reliable method for claustrum localization across age in mice.","authors":"Tarek Shaker, Gwyneth J Dagpa, Vanessa Cattaud, Brian A Marriott, Mariam Sultan, Mohammed Almokdad, Jesse Jackson","doi":"10.1186/s13041-024-01082-w","DOIUrl":"10.1186/s13041-024-01082-w","url":null,"abstract":"The anatomical organization of the rodent claustrum remains obscure due to lack of clear borders that distinguish it from neighboring forebrain structures. Defining what constitutes the claustrum is imperative for elucidating its functions. Methods based on gene/protein expression or transgenic mice have been used to spatially outline the claustrum but often report incomplete labeling and/or lack of specificity during certain neurodevelopmental timepoints. To reliably identify claustrum projection cells in mice, we propose a simple immunolabelling method that juxtaposes the expression pattern of claustrum-enriched and cortical-enriched markers. We determined that claustrum cells immunoreactive for the claustrum-enriched markers Nurr1 and Nr2f2 are devoid of the cortical marker Tle4, which allowed us to differentiate the claustrum from adjoining cortical cells. Using retrograde tracing, we verified that nearly all claustrum projection neurons lack Tle4 but expressed Nurr1/Nr2f2 markers to different degrees. At neonatal stages between 7 and 21 days, claustrum projection neurons were identified by their Nurr1-postive/Tle4-negative expression profile, a time-period when other immunolabelling techniques used to localize the claustrum in adult mice are ineffective. Finally, exposure to environmental novelty enhanced the expression of the neuronal activation marker c-Fos in the claustrum region. Notably, c-Fos labeling was mainly restricted to Nurr1-positive cells and nearly absent from Tle4-positive cells, thus corroborating previous work reporting novelty-induced claustrum activation. Taken together, this method will aid in studying the claustrum during postnatal development and may improve histological and functional studies where other approaches are not amenable.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"10"},"PeriodicalIF":3.3,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898138","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

In vitro modulation of mTOR and mGlur5 influence α-synuclein accumulation. 体外调节 mTOR 和 mGlur5 会影响 α-突触核蛋白的积累。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-02-15 DOI: 10.1186/s13041-023-01074-2

Viktoria Xing, Kyle Biggar, Stephen S G Ferguson, Shawn Hayley

引用次数: 0

Deleting IP6K1 stabilizes neuronal sodium-potassium pumps and suppresses excitability. 删除 IP6K1 可稳定神经元钠钾泵并抑制兴奋性。

IF 3.6 3区医学

Molecular Brain Pub Date : 2024-02-13 DOI: 10.1186/s13041-024-01080-y

Hongfu Jin, Aili Liu, Alfred C Chin, Chenglai Fu, Hui Shen, Weiwei Cheng

引用次数: 0

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":"17 1","pages":"7"},"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 3.3 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":"17 1","pages":"5"},"PeriodicalIF":3.3,"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 3.3 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":"17 1","pages":"4"},"PeriodicalIF":3.3,"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":"17 1","pages":"3"},"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