Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47.105
Filtrar
1.
Adv Exp Med Biol ; 1175: 15-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583583

RESUMO

As the nervous system evolved from the diffused to centralised form, the neurones were joined by the appearance of the supportive cells, the neuroglia. Arguably, these non-neuronal cells evolve into a more diversified cell family than the neurones are. The first ancestral neuroglia appeared in flatworms being mesenchymal in origin. In the nematode C. elegans proto-astrocytes/supportive glia of ectodermal origin emerged, albeit the ensheathment of axons by glial cells occurred later in prawns. The multilayered myelin occurred by convergent evolution of oligodendrocytes and Schwann cells in vertebrates above the jawless fishes. Nutritive partitioning of the brain from the rest of the body appeared in insects when the hemolymph-brain barrier, a predecessor of the blood-brain barrier was formed. The defensive cellular mechanism required specialisation of bona fide immune cells, microglia, a process that occurred in the nervous system of leeches, bivalves, snails, insects and above. In ascending phylogeny, new type of glial cells, such as scaffolding radial glia, appeared and as the bran sizes enlarged, the glia to neurone ratio increased. Humans possess some unique glial cells not seen in other animals.


Assuntos
Evolução Biológica , Neuroglia/citologia , Animais , Caenorhabditis elegans , Humanos , Bainha de Mielina , Neurônios/citologia , Oligodendroglia/citologia
2.
Adv Exp Med Biol ; 1169: 1-30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487016

RESUMO

In this chapter, heterogeneity is explored in the context of the ventricular-subventricular zone, the largest stem cell niche in the mammalian brain. This niche generates up to 10,000 new neurons daily in adult mice and extends over a large spatial area with dorso-ventral and medio-lateral subdivisions. The stem cells of the ventricular-subventricular zone can be subdivided by their anatomical position and transcriptional profile, and the stem cell lineage can also be further subdivided into stages of pre- and post-natal quiescence and activation. Beyond the stem cells proper, additional differences exist in their interactions with other cellular constituents of the niche, including neurons, vasculature, and cerebrospinal fluid. These variations in stem cell potential and local interactions are discussed, as well as unanswered questions within this system.


Assuntos
Encéfalo , Ventrículos Laterais , Células-Tronco Neurais , Nicho de Células-Tronco , Animais , Encéfalo/citologia , Linhagem da Célula , Ventrículos Laterais/citologia , Camundongos , Células-Tronco Neurais/citologia , Neurônios/citologia , Nicho de Células-Tronco/fisiologia
3.
Adv Exp Med Biol ; 1169: 31-53, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487017

RESUMO

The discovery of neural stem cells in the adult mammalian hippocampus has attracted attention and controversy, which both continue to this day. Hippocampal neural stem cells and their immediate progeny, amplifying neuroprogenitor cells, give rise to neurons and astrocytes in the region. Envisioned as possible key for tissue regeneration, whether mobilized endogenously or transplanted exogenously, neural stem cells have been in the eye of both public and science over the course of the past 20 years. These cells are a heterogeneous population, and here, we review different aspects of their heterogeneity from morphology to metabolism and response to different stimuli.


Assuntos
Hipocampo , Células-Tronco Neurais , Animais , Astrócitos/citologia , Diferenciação Celular , Hipocampo/citologia , Humanos , Células-Tronco Neurais/citologia , Neurogênese , Neurônios/citologia
4.
Nihon Yakurigaku Zasshi ; 154(3): 133-137, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527363

RESUMO

Hydrogen sulfide (H2S) has been focused as a biological mediator, which modulates signal transduction and protects cells and tissues from oxidative stress. H2S is also expected as a neuroprotectant because it has a neuroprotective activity. Endogenous H2S is mainly generated from L-cysteine. However, it is difficult to use L-cysteine as a neuroprotectant because of its neurotoxicity. In 2013, a novel biogenesis pathway of H2S from D-cysteine has been identified. In this pathway, D-amino acid oxidase (DAO) converts D-cysteine to 3-mercaptopyruvate (3MP), followed by the generation of H2S from 3MP by 3-mercaptopyrvate sulfurtransferase. DAO is especially abundant in cerebellum among various brain regions and mediates efficient generation of H2S from D-cysteine in the cerebellar tissues. In addition, D-cysteine has more potent neuroprotective activity in cerebellar primary neurons than L-cysteine. Cerebella Purkinje cells (PCs) are characterized by the highly-branched dendrites and are important for cerebellar functions. The dendritic shrinkage and degeneration of PCs are frequently observed in patients and model mice of cerebellar ataxias. We revealed that D-cysteine enhanced dendritic development of primary cultured PCs, but L-cysteine impaired the dendritic development. This effect of D-cysteine was inhibited by DAO inhibitors and reproduced by 3MP and a H2S donor, suggesting that this enhancement of dendritic development is caused by the production of H2S from D-cysteine. Taken together, D-cysteine would be available as a neuroprotectant against cerebellar ataxias, which are accompanied with dendritic shrinkage of cerebellar PCs.


Assuntos
Cisteína/metabolismo , Sulfeto de Hidrogênio/metabolismo , Neurônios/citologia , Fármacos Neuroprotetores/metabolismo , Animais , Células Cultivadas , D-Aminoácido Oxidase/antagonistas & inibidores , D-Aminoácido Oxidase/metabolismo , Humanos , Camundongos , Neurogênese , Estresse Oxidativo , Células de Purkinje/citologia
5.
Dokl Biochem Biophys ; 486(1): 184-186, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367817

RESUMO

To perform optogenetic prosthetics of the retinal ganglion cell receptive field, a bicistronic genetic construct carrying the genes encoding the excitatory (channelrhodopsin-2) and inhibitory (Guillardia theta anion channelrhodopsin GtACR2) rhodopsins was created. A characteristic feature of this construct was the combination of these two genes with a mutant IRES insertion between them, which ensures the exact ratio of expression levels of the first and second genes in each transfected cell. Illumination of the central part of the neuron with light with a wavelength of 470 nm induced the action potential generation in the cell. Stimulation of the peripheral neuronal region with light induced the inhibition of action potential generation. Thus, using optogenetics methods, we simulated the ON-OFF interaction in the retinal ganglion cell receptive field. Theoretically, this construct can be used for optogenetic prosthetics of degenerative retina in the case of its delivery to the ganglion cells with lentiviral vectors.


Assuntos
Channelrhodopsins/genética , Optogenética/métodos , Retina/patologia , Células Ganglionares da Retina/metabolismo , Animais , Luz , Neurônios/citologia , Neurônios/metabolismo , Neurônios/efeitos da radiação , Ratos , Retina/efeitos da radiação , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/efeitos da radiação , Transfecção
6.
Results Probl Cell Differ ; 67: 337-357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31435802

RESUMO

Neurons are polarized cells with long branched axons and dendrites. Microtubule generation and organization machineries are crucial to grow and pattern these complex cellular extensions. Microtubule organizing centers (MTOCs) concentrate the molecular machinery for templating microtubules, stabilizing the nascent polymer, and organizing the resultant microtubules into higher-order structures. MTOC formation and function are well described at the centrosome, in the spindle, and at interphase Golgi; we review these studies and then describe recent results about how the machineries acting at these classic MTOCs are repurposed in the postmitotic neuron for axon and dendrite differentiation. We further discuss a constant tug-of-war interplay between different MTOC activities in the cell and how this process can be used as a substrate for transcription factor-mediated diversification of neuron types.


Assuntos
Diferenciação Celular , Centro Organizador dos Microtúbulos/metabolismo , Neurônios/citologia , Axônios , Centrossomo , Microtúbulos
7.
Results Probl Cell Differ ; 67: 359-375, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31435803

RESUMO

Neurons forming the central nervous system are generated by neural stem and progenitor cells, via a process called neurogenesis (Götz and Huttner, Nat Rev Mol Cell Biol, 6:777-788, 2005). In this book chapter, we focus on neurogenesis in the dorsolateral telencephalon, the rostral-most region of the neural tube, which contains the part of the central nervous system that is most expanded in mammals (Borrell and Reillo, Dev Neurobiol, 72:955-971, 2012; Wilsch-Bräuninger et al., Curr Opin Neurobiol 39:122-132, 2016). We will discuss recent advances in the dissection of the cell biological mechanisms of neurogenesis, with particular attention to the organization and function of the Golgi apparatus and its relationship to the centrosome.


Assuntos
Polaridade Celular , Complexo de Golgi/metabolismo , Células-Tronco Neurais/citologia , Células Neuroepiteliais/citologia , Neurogênese , Neurônios/citologia , Animais , Centrossomo
8.
Adv Exp Med Biol ; 1155: 869-874, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468453

RESUMO

Our group previously reported that taurine has a protective capacity on the hippocampus and cerebellum of arsenic (As)-exposed mouse. In the present study, we explore whether taurine demonstrates protection against As toxicity in primary cortical neurons. Primary cortical neurons were exposed to various concentrations of arsenite and cell viability was assessed to confirm the toxicity of As on cortical neurons. The protection of taurine was examined after primary cortical neurons were treating with arsenite and taurine for 24 h. The cell viability was examined by MTT and caspase-3 activity assay. The expression of Bax and Bcl-2 was determined by western blot. The results showed that As exposure reduced cell viability and enhanced the activity of caspase-3, which were markedly inhibited by taurine treatment. The expression of Bax and Bcl-2 were disturbed by As exposure, which were reversed by taurine. These results indicated that taurine expose protective effect on As-exposed primary cortical neurons and its mechanism maybe involved the regulation of Bax/Bcl-2.


Assuntos
Arsênico/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Taurina/farmacologia , Animais , Apoptose , Sobrevivência Celular , Células Cultivadas , Camundongos , Neurônios/citologia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
9.
Adv Exp Med Biol ; 1155: 923-934, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468457

RESUMO

Diabetic neuropathy (DN) is the most common chronic complication of DM and its major pathological changes show axonal dysfunction, atrophy and loss. However, there are few reports that taurine promotes neurite growth of dorsal root ganglion (DRG) cells. In current study, DRG neurons were exposed to high glucose (HG) with or without taurine. The neurite outgrowth of DRG neurons was observed by fluorescent immunohistochemistry method. Expression of Gap-43, Akt, phosphorylated Akt, mTOR and phosphorylated mTOR was determined by Western blot assay. Our results showed that HG significantly decreased the neurite outgrowth and expression of Gap-43 in DRG neurons. Moreover, phosphorylated levels of Akt and mTOR were downregulated in DRG neurons exposed to HG. On the contrary, taurine supplementation significantly reversed the decreased neurite outgrowth and Gap-43 expression, and the downregulated phosphorylated levels of Akt and mTOR. However, the protective effects of taurine were blocked in the presence of PI3K antagonists LY294002 or Akt antagonists Perifosine. These results indicate that taurine promotes neurite outgrowth of DRG neurons exposed to HG via activating Akt/mTOR signal pathway.


Assuntos
Gânglios Espinais/citologia , Neurônios/efeitos dos fármacos , Taurina/farmacologia , Células Cultivadas , Proteína GAP-43/metabolismo , Glucose , Humanos , Neuritos/efeitos dos fármacos , Neurônios/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
10.
Sheng Li Xue Bao ; 71(4): 527-536, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440749

RESUMO

The aim of this study was to investigate whether G protein-coupled estrogen receptor (GPER) could alleviate hippocampal neuron injury under cerebral ischemia-reperfusion injury (CIRI) by acting on endoplasmic reticulum stress (ERS). The CIRI animal model was established by middle cerebral artery occlusion (MCAO). Female ovariectomized (OVX) Sprague-Dawley (SD) female rats were randomly divided into 4 groups: control, ischemia-reperfusion injury (MCAO), vehicle (MCAO+DMSO), and GPER-specific agonist G1 (MCAO+G1) groups. The neurobehavioral score was assessed by the Longa score method, the morphological changes of the neurons were observed by the Nissl staining, the cerebral infarction was detected by the TTC staining, and the neural apoptosis in the hippocampal CA1 region was detected by TUNEL staining. The distribution and expression of GRP78 (78 kDa glucose-regulated protein 78) in the hippocampal CA1 region were observed by immunofluorescent staining. The protein expression levels of GRP78, Caspase-12, CHOP and Caspase-3 were detected by Western blot, and the mRNA expression levels of GRP78, Caspase-12, and CHOP were detected by the real-time PCR. The results showed that the neurobehavioral score, cerebral infarct volume, cellular apoptosis index, as well as GRP78, Caspase-12 and CHOP protein and mRNA expression levels in the MCAO group were significantly higher than those of control group. And G1 reversed the above-mentioned changes in the MCAO+G1 group. These results suggest that the activation of GPER can decrease the apoptosis of hippocampal neurons and relieve CIRI, and its mechanism may involve the inhibition of ERS.


Assuntos
Isquemia Encefálica , Estresse do Retículo Endoplasmático , Neurônios/citologia , Receptores Estrogênicos/fisiologia , Receptores Acoplados a Proteínas-G/agonistas , Traumatismo por Reperfusão , Animais , Apoptose , Região CA1 Hipocampal/citologia , Caspase 12/metabolismo , Caspase 3/metabolismo , Feminino , Proteínas de Choque Térmico/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismo
11.
Sheng Li Xue Bao ; 71(4): 597-603, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440757

RESUMO

Central nervous system injury leads to irreversible neuronal loss and glial scar formation, which ultimately results in persistent neurological dysfunction. Regenerative medicine suggests that replenishing missing neurons may be an ideal approach to repair the damage. Recent researches showed that many mature cells could be transdifferentiated into functional neurons by reprogramming. Therefore, reprogramming endogenous glia in situ to produce functional neurons shows great potential and unique advantage for repairing neuronal damage and treating neurodegenerative diseases. The present review summarized the current research progress on in situ transdifferentiation in the central nervous system, focusing on the cell types, characteristics and research progress of glial cells that could be transdifferentiated in situ, in order to provide theoretical basis for the development of new therapeutic strategies of neuronal injury and further clinical application.


Assuntos
Transdiferenciação Celular , Reprogramação Celular , Sistema Nervoso Central/citologia , Neuroglia/citologia , Neurônios/citologia , Humanos , Doenças Neurodegenerativas
12.
Chem Biodivers ; 16(8): e1900299, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31287220

RESUMO

The biotransformation of huperzine B (hupB), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. One new compound, 8α,15α-epoxyhuperzine B (1), along with two known oxygenated hupB analogs, 16-hydroxyhuperzine B (2) and carinatumin B (3), was isolated and identified. The structures of all the isolates were deduced by spectroscopic methods including NMR, MS, IR, and UV spectra. The known compounds 2 and 3 were obtained from a microbial source for the first time. To the best of our knowledge, it is the first report on the microbial transformation of hupB and would facilitate further structural modification of hupB by chemo-enzymatic method. In the LPS-induced neuro-inflammation injury assay, 8α,15α-epoxyhuperzine B (1) exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with an EC50 of 40.1 nm.


Assuntos
Alcaloides/química , Huperzia/química , Alcaloides/metabolismo , Alcaloides/farmacologia , Biotransformação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Huperzia/metabolismo , Lipopolissacarídeos/toxicidade , Conformação Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia
13.
Genome Biol ; 20(1): 142, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315641

RESUMO

We develop CellSIUS (Cell Subtype Identification from Upregulated gene Sets) to fill a methodology gap for rare cell population identification for scRNA-seq data. CellSIUS outperforms existing algorithms for specificity and selectivity for rare cell types and their transcriptomic signature identification in synthetic and complex biological data. Characterization of a human pluripotent cell differentiation protocol recapitulating deep-layer corticogenesis using CellSIUS reveals unrecognized complexity in human stem cell-derived cellular populations. CellSIUS enables identification of novel rare cell populations and their signature genes providing the means to study those populations in vitro in light of their role in health and disease.


Assuntos
Análise de Célula Única/métodos , Transcriptoma , Algoritmos , Linhagem Celular , Humanos , Neurônios/citologia
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(3): 256-261, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31257809

RESUMO

OBJECTIVE: To investigate the effects of optical genetic techniques on new neurons through the Wnt/ß-Catenin pathway. METHODS: Neural stem cells (ESCs)were extracted from the cerebral cortex of fetal rat and transfected by lentivirus carrying DCX-ChR2-EGFP gene and the expression of DCX of newborn neurons differentiated from neural stem cells were observed. All cells were divided into 3 groups(n=9): control group, NSCs+EGFP and NSCs+ChR2 groups. The control group was normal cultured NSCs (NSCs group); the neural stem cells in NSCs+EGFP group were transfected with lentivirus carrying EGFP gene. The neural stem cells in NSCs+ChR2 group were infected with lentivirus carrying DCX-ChR2-EGFP gene. After 48 hours of lentivirus infection, 470 nm blue laser irradiation was performed for 3 consecutive days. NeuN+ positive cell density(the maturation of neural stem cells)and the ratio of NeuN+/Hoechst in each group were observed. Western blot was used to detect the expression levels of MAP2, NeuN, Neurog2, NeuroD1 and GluR2. Western blot was used to detect the expressions of ß-catenin and TCF4 associated with Wnt/ß-catenin signaling channel. Verapamil (100 µmol/L, L-type calcium channel blockers) and Dkk1 (50 µg/ml, ß-catenin inhibitor) were used to treat stem cells of the NSCs+ChR2 group and then the expressions of MAP2, NeuN, Neurog2, NeuroD1 and GluR were detected by Western blot. RESULTS: After 3 days of 470 nm blue laser irradiation, NeuN+ positive cell density(the maturation of neural stem cells)and the ratio of NeuN+/Hoechst, the expression levels of the protein MAP2, NeuN, Neurog2, NeuroD1, GluR and the protein ß-catenin and TCF4 associated with Wnt/ß-catenin signaling channel detected by Western blot were significantly increased in the group of NSCs+ChR2, compared with NSCs and NSCs+EGFP groups. The expressions of MAP2, NeuN, Neurog2, NeuroD1 and GluR were remarkably decreased after treated by verapamil and Dkk1 in the group of NSCs+ChR2. It was proved that the opening of ChR2 channel producing cationic influx promoted the maturation of neural stem cells and induced by the Wnt/ß-catenin signaling pathway. CONCLUSION: Optical genetic promoted the maturation of newborn neurons through the Wnt/ß-catenin signaling pathway.


Assuntos
Células-Tronco Neurais/citologia , Neurônios/citologia , Optogenética , Via de Sinalização Wnt , Animais , Células Cultivadas , Ratos , Transfecção
15.
Nat Commun ; 10(1): 2907, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266958

RESUMO

Single-nucleus RNA-seq (snRNA-seq) enables the interrogation of cellular states in complex tissues that are challenging to dissociate or are frozen, and opens the way to human genetics studies, clinical trials, and precise cell atlases of large organs. However, such applications are currently limited by batch effects, processing, and costs. Here, we present an approach for multiplexing snRNA-seq, using sample-barcoded antibodies to uniquely label nuclei from distinct samples. Comparing human brain cortex samples profiled with or without hashing antibodies, we demonstrate that nucleus hashing does not significantly alter recovered profiles. We develop DemuxEM, a computational tool that detects inter-sample multiplets and assigns singlets to their sample of origin, and validate its accuracy using sex-specific gene expression, species-mixing and natural genetic variation. Our approach will facilitate tissue atlases of isogenic model organisms or from multiple biopsies or longitudinal samples of one donor, and large-scale perturbation screens.


Assuntos
Anticorpos/análise , Núcleo Celular/genética , Genômica/métodos , Análise de Célula Única/métodos , Idoso , Idoso de 80 Anos ou mais , Animais , Núcleo Celular/química , Núcleo Celular/metabolismo , DNA/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/química , Neurônios/citologia , Neurônios/metabolismo , Córtex Pré-Frontal/química , Córtex Pré-Frontal/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2588-2593, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359728

RESUMO

The PK-PD correlation models by using pharmacodynamics and pharmacokinetics were applied to study the material basis of Naomaitong,a clinical empirical prescription for the treatment of cerebral apoplexy,in inhibiting the death of PC12 nerve cells induced by Na_2S_2O_4 and Glu. In this experiment,PC12 cell death models induced by Na_2S_2O_4 and Glu were established respectively.With LDH lateral leakage and NO content as pharmacodynamic indexes,PK-PD model was established by SVM algorithm to evaluate the effective components of Naomaitong in inhibiting neural cell death. The results showed that the positive correlation of emodin methyl ether-8-O-ß-D-glucopyranoside,aloe emodin,chrysophanol,rhein,emodin,ginsenoside Rg1,ginsenoside Rc,3'-methoxypuerarin and ligustilide was significant,obviously improving the LDH release and NO content. The results indicated that the contribution of Radix Puerariae Lobatae Radix and Rhei Radix et Rhizoma in Naomaitong could protect the nerve cell death induced by Na_2S_2O_4 and Glu respectively. PK-PD model was used to screen the neuroprotective components in Naomaitong,revealing the possible pharmacodynamic material basis of Naomaitong in the treatment of cerebral ischemia injury.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Animais , Células PC12 , Ratos
17.
Nature ; 571(7765): 349-354, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292549

RESUMO

Ascidian embryos highlight the importance of cell lineages in animal development. As simple proto-vertebrates, they also provide insights into the evolutionary origins of cell types such as cranial placodes and neural crest cells. Here we have determined single-cell transcriptomes for more than 90,000 cells that span the entirety of development-from the onset of gastrulation to swimming tadpoles-in Ciona intestinalis. Owing to the small numbers of cells in ascidian embryos, this represents an average of over 12-fold coverage for every cell at every stage of development. We used single-cell transcriptome trajectories to construct virtual cell-lineage maps and provisional gene networks for 41 neural subtypes that comprise the larval nervous system. We summarize several applications of these datasets, including annotating the synaptome of swimming tadpoles and tracing the evolutionary origin of cell types such as the vertebrate telencephalon.


Assuntos
Linhagem da Célula/genética , Ciona intestinalis/citologia , Ciona intestinalis/genética , Análise de Célula Única , Transcriptoma , Animais , Sequência de Bases , Evolução Biológica , Ciona intestinalis/classificação , Ciona intestinalis/crescimento & desenvolvimento , Gastrulação , Redes Reguladoras de Genes , Larva/citologia , Larva/genética , Sistema Nervoso/citologia , Sistema Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Notocorda/citologia , Notocorda/embriologia , Especificidade de Órgãos , Sinapses/genética , Sinapses/metabolismo
18.
Nat Commun ; 10(1): 2693, 2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217419

RESUMO

The kinesin-3 KIF1C is a fast organelle transporter implicated in the transport of dense core vesicles in neurons and the delivery of integrins to cell adhesions. Here we report the mechanisms of autoinhibition and release that control the activity of KIF1C. We show that the microtubule binding surface of KIF1C motor domain interacts with its stalk and that these autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21. The FERM domain of PTPN21 stimulates dense core vesicle transport in primary hippocampal neurons and rescues integrin trafficking in KIF1C-depleted cells. In vitro, human full-length KIF1C is a processive, plus-end directed motor. Its landing rate onto microtubules increases in the presence of either PTPN21 FERM domain or the cargo adapter Hook3 that binds the same region of KIF1C tail. This autoinhibition release mechanism allows cargo-activated transport and might enable motors to participate in bidirectional cargo transport without undertaking a tug-of-war.


Assuntos
Cinesina/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Vesículas Citoplasmáticas/metabolismo , Hipocampo/citologia , Humanos , Integrinas/metabolismo , Microscopia Intravital/métodos , Cinesina/genética , Cinesina/isolamento & purificação , Camundongos , Proteínas Associadas aos Microtúbulos/isolamento & purificação , Microtúbulos/metabolismo , Neurônios/citologia , Cultura Primária de Células , Ligação Proteica , Domínios Proteicos , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteínas Tirosina Fosfatases não Receptoras/isolamento & purificação , RNA Interferente Pequeno/metabolismo , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Imagem Individual de Molécula/métodos
19.
Nat Commun ; 10(1): 2736, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227718

RESUMO

Reconstruction and annotation of volume electron microscopy data sets of brain tissue is challenging but can reveal invaluable information about neuronal circuits. Significant progress has recently been made in automated neuron reconstruction as well as automated detection of synapses. However, methods for automating the morphological analysis of nanometer-resolution reconstructions are less established, despite the diversity of possible applications. Here, we introduce cellular morphology neural networks (CMNs), based on multi-view projections sampled from automatically reconstructed cellular fragments of arbitrary size and shape. Using unsupervised training, we infer morphology embeddings (Neuron2vec) of neuron reconstructions and train CMNs to identify glia cells in a supervised classification paradigm, which are then used to resolve neuron reconstruction errors. Finally, we demonstrate that CMNs can be used to identify subcellular compartments and the cell types of neuron reconstructions.


Assuntos
Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais (Computação) , Neurônios/citologia , Sinapses , Algoritmos , Animais , Encéfalo/citologia , Conjuntos de Dados como Assunto , Estudos de Viabilidade , Masculino , Microscopia Eletrônica , Passeriformes
20.
Chem Biol Interact ; 309: 108686, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31152735

RESUMO

Acetylcholinesterase (EC3.1.1.7; AChE) is a key enzyme in the cholinergic system. Emerging evidence has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a typical persistent organic pollutant, suppressed neuronal AChE activity via dysregulation of different biosynthesis processes in human and rat neuronal cells. In the nervous system, astrocytes protect neurons from environmental pollutants. As a known target cell of TCDD, the astrocyte might be involved in TCDD effects on neuronal AChE. Therefore, in the present study, we found astrocyte-derived conditioned medium (ACM) could induce AChE activity preferentially in mature neurons in the absence of TCDD. The enzymatic activity of AChE was generally decreased in cultured cortical neurons upon direct treatment with TCDD (0.003-0.01 nM). This trend of changes in AChE activity was not significantly altered in immature neurons exposed to ACM produced in the presence of TCDD (TACM group), but reversed in mature neurons. Compared with effects of treatment with ACM plus TCDD (ACMT), a significant differential effect on AChE activity was found in the TACM group in response to TCDD treatment specifically in immature neurons, suggesting the presence of a TCDD-specific active component derived from the astrocyte. Inconsistent alterations in expression and enzymatic activities of the AChE T subunit (AChET) and the proline-rich membrane anchor (PRiMA) were found, suggesting that a mechanism of action beyond the transcriptional level might be involved. These data indicate that the astrocyte might play a protective role in TCDD-induced alterations of neuronal AChE in certain stages of differentiation.


Assuntos
Acetilcolinesterase/metabolismo , Meios de Cultivo Condicionados/química , Expressão Gênica/efeitos dos fármacos , Dibenzodioxinas Policloradas/farmacologia , Acetilcolinesterase/genética , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Dibenzodioxinas Policloradas/química , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA