Journal of Experimental Neuroscience最新文献_第10页

Tau: A Common Denominator and Therapeutic Target for Neurodegenerative Disorders. Tau:神经退行性疾病的共同特征和治疗靶点。

Journal of Experimental Neuroscience Pub Date : 2018-05-01 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518772380

Alexander Maxan, Francesca Cicchetti

引用次数: 8

An Efficient System for Gene Perturbation in Embryonic Hippocampal Progenitors Using Ex Vivo Electroporation Followed by In Vitro Dissociated Cell Culture. 利用离体电穿孔和体外分离细胞培养对胚胎海马祖细胞进行基因扰动的有效系统。

Journal of Experimental Neuroscience Pub Date : 2018-04-19 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518767404

Bhavana Muralidharan, Leora D'Souza, Shubha Tole

{"title":"An Efficient System for Gene Perturbation in Embryonic Hippocampal Progenitors Using Ex Vivo Electroporation Followed by In Vitro Dissociated Cell Culture.","authors":"Bhavana Muralidharan, Leora D'Souza, Shubha Tole","doi":"10.1177/1179069518767404","DOIUrl":"https://doi.org/10.1177/1179069518767404","url":null,"abstract":"We established an efficient cell culture assay that permits combinatorial genetic perturbations in hippocampal progenitors to examine cell-autonomous mechanisms of fate specification. The procedure begins with ex vivo electroporation of isolated, intact embryonic brains, in a manner similar to in utero electroporation but with greatly improved access and targeting. The electroporated region is then dissected and transiently maintained in organotypic explant culture, followed by dissociation and plating of cells on coverslips for in vitro culture. This assay recapitulates data obtained in vivo with respect to the neuron-glia cell fate switch and can be effectively used to test intrinsic or extrinsic factors that regulate this process. The advantages of this ex vivo procedure over in utero electroporation include the fact that distinct combinations of perturbative reagents can be introduced in different embryos from a single litter, and issues related to embryonic lethality of transgenic animals can be circumvented.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518767404"},"PeriodicalIF":0.0,"publicationDate":"2018-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518767404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36098444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Test for Non-Synergistic Interactions in Phytomedicine, Just as You Do for Isolated Compounds. 测试植物药物中的非协同相互作用，就像你对分离化合物所做的那样。

Journal of Experimental Neuroscience Pub Date : 2018-04-18 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518767654

Areeba Patel, Farooq Ali Khan, Arindam Sikdar, Amit Mondal, Sunil Dutt Shukla, Sukant Khurana

{"title":"Test for Non-Synergistic Interactions in Phytomedicine, Just as You Do for Isolated Compounds.","authors":"Areeba Patel, Farooq Ali Khan, Arindam Sikdar, Amit Mondal, Sunil Dutt Shukla, Sukant Khurana","doi":"10.1177/1179069518767654","DOIUrl":"https://doi.org/10.1177/1179069518767654","url":null,"abstract":"Phytomedicine has often been used as \"alternative therapy,\" which in our opinion is unfortunate as it prevents its main actions being systematically studied, side effects explored, and toxicity tested, like all single-compound-based medicine. Our group is interested in finding which traditional or modern phytomedicines actually work and which are simply \"working\" through placebo, standardizing phytomedicine preparations, studying their toxicity, and finding active molecules in plants for modification and chemical synthesis as single compounds. Although fluctuation in efficacy due to seasonal and geographical variations in phytomedicine remains a concern, if well regulated, even plant extracts without isolated compounds can serve medicinal needs where single-compound options are currently not great. A potential concern with such phytomedicine is frequent mixing of ingredients in commercial formulations without test of synergism. Our study on the use of 2 traditional plants for Parkinson disease shows a clear lack of synergism, and to study nonsynergism better, we developed a new visualization approach. In this commentary, using our study on Parkinson disease as an example, we make a case for better evaluation of phytomedicines, especially testing for synergistic interactions. We also critique our own exploration of oxidative stress and few behavioral parameters alone to lay grounds for what we and hopefully others can do in future to extract more information from their phytomedicine studies. We hope this commentary acts as a good warning for anyone mixing 2 phytomedicines without testing.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518767654"},"PeriodicalIF":0.0,"publicationDate":"2018-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518767654","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36053671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

β-Guanidinopropionic Acid Stimulates Brain Mitochondria Biogenesis and Alters Cognitive Behavior in Nondiseased Mid-Age Mice. β-胍丙酸刺激未患病中年小鼠脑线粒体生物发生并改变认知行为

Journal of Experimental Neuroscience Pub Date : 2018-04-02 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518766524

Artem P Gureev, Ekaterina A Shaforostova, Anatoly A Starkov, Vasily N Popov

{"title":"β-Guanidinopropionic Acid Stimulates Brain Mitochondria Biogenesis and Alters Cognitive Behavior in Nondiseased Mid-Age Mice.","authors":"Artem P Gureev, Ekaterina A Shaforostova, Anatoly A Starkov, Vasily N Popov","doi":"10.1177/1179069518766524","DOIUrl":"https://doi.org/10.1177/1179069518766524","url":null,"abstract":"β-guanidinopropionic acid (β-GPA) has been used as a nutritional supplement for increasing physical strength and endurance with positive and predictable results. In muscles, it works as a nonadaptive stimulator of mitochondria biogenesis; it also increases lipid metabolism. There are data indicating that β-GPA can be also neuroprotective, but its mechanisms of action in the brain are less understood. We studied the effects of β-GPA on animal behavior and mitochondrial biogenesis in the cortex and midbrain of mid-age healthy mice. We found that even short-term 3-week-long β-GPA treatment increased the mitochondrial DNA (mtDNA) copy number in the cortex and ventral midbrain, as well as the expression of several key antioxidant and metabolic enzymes-indicators of mitochondria proliferation and the activation of Nrf2/ARE signaling cascade. At the same time, β-GPA downregulated the expression of the β-oxidation genes. Administration of β-GPA in mice for 3 weeks improved the animals' physical strength and endurance health, ie, increased their physical strength and endurance and alleviated anxiety. Thus, β-GPA might be considered an adaptogene affecting both the muscle and brain metabolism in mammals.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518766524"},"PeriodicalIF":0.0,"publicationDate":"2018-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518766524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35993646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

AP2γ: A New Player on Adult Hippocampal Neurogenesis Regulation. AP2γ:成人海马神经发生调控的新参与者

Journal of Experimental Neuroscience Pub Date : 2018-04-02 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518766897

Antonio Mateus-Pinheiro, Nuno Dinis Alves, Nuno Sousa, Luisa Pinto

{"title":"AP2γ: A New Player on Adult Hippocampal Neurogenesis Regulation.","authors":"Antonio Mateus-Pinheiro, Nuno Dinis Alves, Nuno Sousa, Luisa Pinto","doi":"10.1177/1179069518766897","DOIUrl":"https://doi.org/10.1177/1179069518766897","url":null,"abstract":"Since the recognition that the mammalian brain retains the ability to generate newborn neurons with functional relevance throughout life, the matrix of molecular regulators that govern adult neurogenesis has been the focus of much interest. In a recent study published in Molecular Psychiatry, we demonstrate Activating Protein 2γ (AP2γ), a transcription factor previously implicated in cell fate determination in the developing cortex, as a novel player in the regulation of glutamatergic neurogenesis in the adult hippocampus. Using distinct experimental approaches, we showed that AP2γ is specifically present in a subpopulation of transient amplifying progenitors, where it acts as a crucial promoter of proliferation and differentiation of adult-born glutamatergic granule neurons. Strikingly, deficiency of AP2γ in the adult brain compromises the generation of new glutamatergic neurons, with impact on the function of cortico-limbic circuits. Here, we share our view on how AP2γ integrates the transcriptional orchestration of glutamatergic neurogenesis in the adult hippocampus, and consequently, how it emerges as a novel molecular candidate to study the translation of environmental pressures into alterations of brain neuroplasticity in homeostatic, but also in neuropathological contexts.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518766897"},"PeriodicalIF":0.0,"publicationDate":"2018-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518766897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35993647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

The Role for Exosomal microRNAs in Disruption of Regulatory T Cell Homeostasis in Multiple Sclerosis. 外泌体microrna在多发性硬化症调节性T细胞稳态破坏中的作用。

Journal of Experimental Neuroscience Pub Date : 2018-03-26 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518764892

Kimitoshi Kimura, Hirohiko Hohjoh, Takashi Yamamura

{"title":"The Role for Exosomal microRNAs in Disruption of Regulatory T Cell Homeostasis in Multiple Sclerosis.","authors":"Kimitoshi Kimura, Hirohiko Hohjoh, Takashi Yamamura","doi":"10.1177/1179069518764892","DOIUrl":"https://doi.org/10.1177/1179069518764892","url":null,"abstract":"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which myelin and oligodendrocytes are the main targets recognized by inflammatory CD4+ T cells reactive to myelin peptides. Regulatory CD4+ T (Treg) cells normally keep homeostasis of the immune system by inhibiting detrimental effects of inflammatory T cells. However, Treg cells are reduced in patients with MS for unknown reason. This commentary highlights a novel function of circulating exosomes to inhibit the differentiation of Treg cells in MS. Our recent work has demonstrated that the circulating exosomes, a member of extracellular vesicles, of patients with MS exert this effect by transferring let-7i to naive CD4+ T cells. The transferred let-7i subsequently causes a decreased expression of insulin like growth factor 1 receptor (IGF1R) and transforming growth factor β receptor 1 (TGFBR1), leading to the inhibition of Treg cell differentiation. Thus, extrinsic microRNAs transferred by exosomes might have an active role in triggering autoimmune diseases. We hypothesize that extracellular vesicles including exosomes can be a communication tool between the gut microbiota and the host immune system. Further research in this area will expand the knowledge about the precise mechanism of autoimmune diseases and can lead to a new therapeutic approach.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518764892"},"PeriodicalIF":0.0,"publicationDate":"2018-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518764892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35981326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Targeting Histone Demethylase LSD1/KDM1a in Neurodegenerative Diseases. 靶向组蛋白去甲基酶LSD1/KDM1a在神经退行性疾病中的作用

Journal of Experimental Neuroscience Pub Date : 2018-03-20 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518765743

Susanna Ambrosio, Barbara Majello

引用次数: 14

The Convergence of Dopamine and α-Synuclein: Implications for Parkinson's Disease. 多巴胺和α-突触核蛋白的聚合:对帕金森病的影响。

Journal of Experimental Neuroscience Pub Date : 2018-03-08 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518761360

Danielle E Mor, Harry Ischiropoulos

{"title":"The Convergence of Dopamine and α-Synuclein: Implications for Parkinson's Disease.","authors":"Danielle E Mor, Harry Ischiropoulos","doi":"10.1177/1179069518761360","DOIUrl":"https://doi.org/10.1177/1179069518761360","url":null,"abstract":"In Parkinson's disease (PD), the loss of dopamine-producing neurons in the substantia nigra (SN) leads to severe motor impairment, and pathological inclusions known as Lewy bodies contain aggregated α-synuclein protein. The relationship of α-synuclein aggregation and dopaminergic degeneration is unclear. This commentary highlights a recent study showing that the interaction of α-synuclein with dopamine may be an important mechanism underlying disease. Elevating dopamine levels in mice expressing human α-synuclein with the A53T familial PD mutation recapitulated key features of PD, including progressive neurodegeneration of the SN and decreased ambulation. The toxicity of dopamine was dependent on α-synuclein expression; hence, raising dopamine levels in nontransgenic mice did not result in neuronal injury. This interaction is likely mediated through soluble α-synuclein oligomers, which had modified conformations and were more abundant as a result of dopamine elevation in the mouse brain. Specific mutation of the dopamine interaction motif in the C-terminus of α-synuclein rescued dopamine neurons from degeneration in Caenorhabditis elegans models. Here, these findings are discussed, particularly regarding possible mechanisms of oligomer toxicity, relevance of these models to sporadic and autosomal recessive forms of PD, and implications for current PD treatment.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518761360"},"PeriodicalIF":0.0,"publicationDate":"2018-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518761360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35930170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Single-Cell Transcriptomics Reveals Regulators of Neuronal Migration and Maturation During Brain Development. 单细胞转录组学揭示大脑发育过程中神经元迁移和成熟的调节因子。

Journal of Experimental Neuroscience Pub Date : 2018-03-08 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518760783

Daniel Pensold, Geraldine Zimmer

{"title":"Single-Cell Transcriptomics Reveals Regulators of Neuronal Migration and Maturation During Brain Development.","authors":"Daniel Pensold, Geraldine Zimmer","doi":"10.1177/1179069518760783","DOIUrl":"https://doi.org/10.1177/1179069518760783","url":null,"abstract":"The correct establishment of inhibitory circuits is crucial for cortical functionality and defects during the development of γ-aminobutyric acid-expressing cortical interneurons contribute to the pathophysiology of psychiatric disorders. A critical developmental step is the migration of cortical interneurons from their site of origin within the subpallium to the cerebral cortex, orchestrated by intrinsic and extrinsic signals. In addition to genetic networks, epigenetic mechanisms such as DNA methylation by DNA methyltransferases (DNMTs) are suggested to drive stage-specific gene expression underlying developmental processes. The mosaic structure of the interneuron generating domains producing a variety of interneurons for diverse destinations complicates research on regulatory instances of cortical interneuron migration. To this end, we performed single-cell transcriptome analysis revealing Dnmt1 expression in subsets of migrating interneurons. We found that DNMT1 preserves the migratory morphology in part through transcriptional control over Pak6 that promotes neurite complexity in postmigratory cells. In addition, we identified Ccdc184, a gene of unknown function, to be highly expressed in postmitotic interneurons. Single-cell mRNA sequencing revealed a positive correlation of Ccdc184 with cell adhesion-associated genes pointing to potential implications of CCDC184 in processes relying on cell-cell adhesion-like migration or morphological differentiation of interneurons that deserves further investigations.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518760783"},"PeriodicalIF":0.0,"publicationDate":"2018-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518760783","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35924721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Wrapping Glial Morphogenesis and Signaling Control the Timing and Pattern of Neuronal Differentiation in the Drosophila Lamina. 包裹性胶质细胞的形态发生和信号传导控制果蝇皮层神经元分化的时间和模式。

Journal of Experimental Neuroscience Pub Date : 2018-03-04 eCollection Date: 2018-01-01 DOI: 10.1177/1179069518759294

Anthony M Rossi, Vilaiwan M Fernandes

{"title":"Wrapping Glial Morphogenesis and Signaling Control the Timing and Pattern of Neuronal Differentiation in the Drosophila Lamina.","authors":"Anthony M Rossi, Vilaiwan M Fernandes","doi":"10.1177/1179069518759294","DOIUrl":"https://doi.org/10.1177/1179069518759294","url":null,"abstract":"Various regions of the developing brain coordinate their construction so that the correct types and numbers of cells are generated to build a functional network. We previously discovered that wrapping glia in the Drosophila visual system are essential for coordinating retinal and lamina development. We showed that wrapping glia, which ensheath photoreceptor axons, respond to an epidermal growth factor cue from photoreceptors by secreting insulins. Wrapping glial insulins activate the mitogen-activated protein kinase (MAPK) pathway downstream of insulin receptor in lamina precursors to induce neuronal differentiation. The signaling relay via wrapping glia introduces a delay that allows the lamina to assemble the correct stoichiometry and physical alignment of precursors before differentiating and imposes a stereotyped spatiotemporal pattern that is relevant for specifying the individual lamina neuron fates. Here, we further describe how wrapping glia morphogenesis correlates with the timing of lamina neuron differentiation by 2-photon live imaging. We also show that although MAPK activity in lamina precursors drives neuronal differentiation, the upstream receptor driving MAPK activation in lamina precursors and the ligand secreted by wrapping glia to trigger it differentially affect lamina neuron differentiation. These results highlight differences in MAPK signaling properties and confirm that communication between photoreceptors, wrapping glia, and lamina precursors must be precisely controlled to build a complex neural network.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518759294"},"PeriodicalIF":0.0,"publicationDate":"2018-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518759294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35905358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7