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1.
Science ; 367(6484): 1303-1304, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32193309
2.
Science ; 367(6484): 1372-1376, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32193327

RESUMO

The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating engineered-enzyme targeting and polymer chemistry, we genetically instructed specific living neurons to guide chemical synthesis of electrically functional (conductive or insulating) polymers at the plasma membrane. Electrophysiological and behavioral analyses confirmed that rationally designed, genetically targeted assembly of functional polymers not only preserved neuronal viability but also achieved remodeling of membrane properties and modulated cell type-specific behaviors in freely moving animals. This approach may enable the creation of diverse, complex, and functional structures and materials within living systems.


Assuntos
Compostos de Anilina/química , Ascorbato Peroxidases/genética , Engenharia Genética , Neurônios/fisiologia , Nitrocompostos/química , Fenilenodiaminas/química , Polímeros/química , Potenciais de Ação , Animais , Ascorbato Peroxidases/metabolismo , Caenorhabditis elegans , Membrana Celular/metabolismo , Sobrevivência Celular , Células Cultivadas , Condutividade Elétrica , Células HEK293 , Hipocampo , Humanos , Potenciais da Membrana , Camundongos , Neurônios Motores/fisiologia , Células Musculares/fisiologia , Neurônios/enzimologia , Técnicas de Patch-Clamp , Polímeros/metabolismo , Ratos , Transdução Genética
3.
Nature ; 579(7798): 256-259, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132709

RESUMO

Most cortical synapses are local and excitatory. Local recurrent circuits could implement amplification, allowing pattern completion and other computations1-4. Cortical circuits contain subnetworks that consist of neurons with similar receptive fields and increased connectivity relative to the network average5,6. Cortical neurons that encode different types of information are spatially intermingled and distributed over large brain volumes5-7, and this complexity has hindered attempts to probe the function of these subnetworks by perturbing them individually8. Here we use computational modelling, optical recordings and manipulations to probe the function of recurrent coupling in layer 2/3 of the mouse vibrissal somatosensory cortex during active tactile discrimination. A neural circuit model of layer 2/3 revealed that recurrent excitation enhances sensory signals by amplification, but only for subnetworks with increased connectivity. Model networks with high amplification were sensitive to damage: loss of a few members of the subnetwork degraded stimulus encoding. We tested this prediction by mapping neuronal selectivity7 and photoablating9,10 neurons with specific selectivity. Ablation of a small proportion of layer 2/3 neurons (10-20, less than 5% of the total) representing touch markedly reduced responses in the spared touch representation, but not in other representations. Ablations most strongly affected neurons with stimulus responses that were similar to those of the ablated population, which is also consistent with network models. Recurrence among cortical neurons with similar selectivity therefore drives input-specific amplification during behaviour.


Assuntos
Modelos Neurológicos , Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Animais , Simulação por Computador , Camundongos , Tato/fisiologia
4.
Zhen Ci Yan Jiu ; 45(1): 33-9, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144906

RESUMO

OBJECTIVE: To explore the effect of moxibustion of acupoints of Governor Vessel on learning-memory ability and expression of the receptor for advanced glycation end products (RAGE), low density lipoprotein (LDL) receptor related protein-1 (LRP-1), ß-amyloid precursor protein (APP) and neuronal ultrastructure of the frontal cortex and hippocampus in vascular dementia (VD) rats, so as to investigate its underlying mechanisms in relieving VD. METHODS: A total of 24 male SD rats were randomized into normal, model, and moxibustion groups (n=8 rats in each group). The VD model was established by occlusion of the bilateral common carotid arteries for 20 min and reperfusion for 10 min which was repeated for 3 times. Moxibustion was applied to "Baihui" (GV20), "Dazhui"(GV14) and "Fengfu"(GV16)for 30 min, once daily for 4 weeks. The learning-memory ability was evaluated by using Morris water maze tests. At the end of experiments, the frontal lobe of cerebral cortex and hippocampus tissues were collected for detecting the expression of RAGE and LRP-1 proteins with Western blot, and RAGE, LRP-1 and APP mRNAs with quantitative real-time PCR, respectively. The ultrastructure of neurons in the frontal cortex and hippocampal CA1 region was observed with transmission electron microscopy. RESULTS: Following modeling, Morris water maze tests showed that the average escape latency of the model group and moxibustion group was significantly prolonged on the 4th day of modeling (P<0.01). The expression levels of RAGE protein and mRNA and APP mRNA were significantly increased (P<0.01), while those of LRP-1 protein and mRNA in the cortex and hippocampus remarkably decreased in the model group relevant to the normal group (P<0.01). Following moxibustion, modeling-induced increase of expression of RAGE protein and mRNA and APP mRNA, and down-regulation of expression of LRP-1 protein and mRNA were reversed in the moxibustion group relevant to the model group (P<0.01). Results of electron microscopy showed dilation of the mitochondria with disappearance of the cristae, partial vacuolar degeneration or dissolved external membrane, and cytoplasmic edema with basic disappearance of the rough endoplasmic reticulum and glycogen particles in neurons of the frontal cortex and hippocampal CA1 region after modeling, which was relatively milder in the moxibustion group. CONCLUSION: Moxibustion of acupoints of the Governor Vessel may reduce the content of APP in the frontal cortex and hippocampus by regulating the expression of RAGE and LRP-1 proteins and mRNA in VD rats.


Assuntos
Demência Vascular , Moxibustão , Animais , Lobo Frontal , Hipocampo , Masculino , Neurônios , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada
5.
Science ; 367(6482): 1105-1112, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139538

RESUMO

The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to the dorsomedial hypothalamus (DMH), a hypothalamic autonomic center. Genetic ablation and optogenetics revealed that the DP/DTT→DMH pathway drives thermogenic, hyperthermic, and cardiovascular sympathetic responses to psychosocial stress without contributing to basal homeostasis. This pathway also mediates avoidance behavior from psychosocial stressors. Given the variety of stress responses driven by the DP/DTT→DMH pathway, the DP/DTT can be a potential target for treating psychosomatic disorders.


Assuntos
Núcleo Hipotalâmico Dorsomedial/metabolismo , Comportamento Social , Estresse Psicológico/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Animais , Emoções/fisiologia , Feminino , Ácido Glutâmico/metabolismo , Homeostase , Masculino , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Prosencéfalo/metabolismo , Transtornos Psicofisiológicos/terapia , Ratos , Ratos Endogâmicos LEC , Ratos Wistar , Transdução de Sinais
6.
Neuron ; 105(3): 395-397, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32027826

RESUMO

A current major challenge lies in controlling molecularly defined brain receptor and channel populations to investigate their function in vivo. In this issue of Neuron, Acosta-Ruiz et al. (2020) developed a highly versatile molecular toolkit to efficiently manipulate specific metabotropic glutamate receptor subtypes in brain circuits with light.


Assuntos
Receptores de Glutamato Metabotrópico , Encéfalo , Ligantes , Neurônios
7.
Neuron ; 105(3): 402-404, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32027829

RESUMO

A vast array of animal behavior-from locomotion to human speech-is thought to consist of different hierarchical levels, but its neural implementation remains poorly understood. In this issue of Neuron, Kaplan et al. (2020) identify neuronal circuit dynamics responsible for multiple levels and timescales of hierarchical locomotion control in Caenorhabditis elegans.


Assuntos
Proteínas de Caenorhabditis elegans , Neurônios , Animais , Caenorhabditis elegans , Humanos , Locomoção , Sistema Nervoso
8.
Neuron ; 105(4): 589-591, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32078790

RESUMO

Balance between excitation and inhibition (E-I balance) in neural circuits is believed to be tightly regulated. To the contrary, in this issue of Neuron, Bridi et al. (2020) reveal that inverse oscillations of synaptic inhibition and excitation lead to peaks and valleys in E-I balance across the 24 h day.


Assuntos
Córtex Visual , Neurônios
9.
Neuron ; 105(4): 591-593, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32078791

RESUMO

In this issue of Neuron, Ashrafi et al. (2020) identify a feedforward signaling mechanism that couples neuronal activity to the homeostatic maintenance of axonal and synaptic ATP production. This mechanism is achieved via changes in cytoplasmic calcium and activation of brain-specific, mitochondrial MICU3.


Assuntos
Cálcio , Transmissão Sináptica , Trifosfato de Adenosina , Homeostase , Neurônios
11.
Artigo em Chinês | MEDLINE | ID: mdl-32074751

RESUMO

Objective: To research the auditory nerve transduction effects under multi-wavelength pulsed laser stimulations within a safe and acceptable signal range. Methods: The real-time detection of intracellular calcium concentration was adopted by specific fluorescent indicator staining based on calcium imager. The spiral ganglion cells of mice were cultured in vitro. After fluorescent indicating, morphologic observation under optical microscope, Fura-2 calcium ion fluorescence excitation, intact morphology cells selection, fixing the optical fiber, the spiral ganglion cells were irradiated by different wavelength laser, including visible light (450 nm) and near infrared light (808 nm,1 065 nm). The intracellular calcium concentration was monitored by calcium ion imaging. Results: When 450 nm laser stimulated spiral ganglion cells, the intracellular calcium concentration was strongly increased, however, for other wavelength laser stimulation, there was no obvious relative response. And the sensitivity expression of the nerve cells under laser was related with the location of laser fiber. Cells closer to the fiber produced more obvious changes in calcium ion concentration, while for cells farther away from the fiber, the change amplitudes were weaker although the number of changes in calcium ion concentration was consistent. Conclusion: The spiral ganglion cells of mice can induce a signal transduction response under the action of laser, and the response has laser wavelength selectivity.


Assuntos
Sinalização do Cálcio , Lasers , Transdução de Sinais , Gânglio Espiral da Cóclea/citologia , Animais , Células Cultivadas , Camundongos , Neurônios , Gânglio Espiral da Cóclea/efeitos da radiação
12.
BMC Med Genet ; 21(1): 26, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32028920

RESUMO

BACKGROUND: While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. METHODS: In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed. RESULTS: A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, 17p13.3 duplication and 3p deletion, were observed in the second case. This double chromosomal aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3,17)(p26.2;p13.3). CONCLUSIONS: 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have an uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums.


Assuntos
Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Lisencefalia/genética , Neurônios/patologia , Translocação Genética/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Proteínas 14-3-3/genética , Moléculas de Adesão Celular/genética , Movimento Celular/genética , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 3/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/diagnóstico , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/fisiopatologia , Hibridização Genômica Comparativa , Contactinas/genética , Feminino , Dosagem de Genes/genética , Estudos de Associação Genética , Humanos , Hibridização in Situ Fluorescente , Lisencefalia/diagnóstico , Lisencefalia/fisiopatologia , Meiose/genética , Proteínas Associadas aos Microtúbulos/genética , Neurônios/metabolismo , Fenótipo , Trissomia/genética
13.
Adv Exp Med Biol ; 1218: 93-101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060873

RESUMO

Notch signaling is required for maintaining neural stem cells (NSCs) in the developing brain. NSCs have potential to give rise to many neuronal types in the early telencephalon, and the potential decreases as embryonic development proceeds. Nepro, which encodes a unique nucleolar protein and is activated downstream of Notch, is essential for maintaining NSCs in the early telencephalon. Nepro is also expressed at basal levels and required for maintaining the preimplantation embryo, by repressing mitochondria-associated p53 apoptotic signaling. Notch signaling also controls dendritic complexity in mitral cells, major projection neurons in the olfactory bulb, showing that many steps of neural development involve Notch signaling.


Assuntos
Blastocisto/citologia , Blastocisto/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Animais , Neurogênese , Neurônios/citologia , Neurônios/metabolismo , Receptores Notch/metabolismo
15.
Adv Clin Exp Med ; 29(1): 135-145, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011832

RESUMO

BACKGROUND: Anesthetics, such as isoflurane, sevoflurane, ketamine, and desflurane, are commonly used in clinics. Specifically, isoflurane is one of the most commonly used inhalational anesthetics, which can be used in surgery patients of all ages, including children. OBJECTIVES: The aim of the study was to investigate the mechanisms of vitexin against isoflurane-induced neurotoxicity. MATERIAL AND METHODS: Reference memory testing was performed for 5 days (4 trials, 2 per day) before anesthesia. Reversal testing was performed on the 3rd day after anesthesia. The cell viability and apoptosis of PC-12 cells were detected using MTT and TUNEL assays, respectively. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum tumor necrosis factor α (TNF­α), interleukin 6 (IL­6), glutathione (GSH), and superoxide dismutase (SOD) concentrations. The concentration of reactive oxygen species (ROS) was detected using ROS measurement. Expression of miR-409 was determined using quantitative reverse-transcription polymerase chain reaction (qPT-PCR). Protein expression levels were detected using western blotting. RESULTS: Rats treated with isoflurane showed significant increases in the escape latency periods (ELP) and the apoptosis of hippocampus neuron cells; this effect was reversed by 3 mg/kg or 10 mg/kg of vitexin (p < 0.05). Further testing showed that isoflurane could significantly decrease the cell viability and increase the apoptosis of PC-12, the expression of inflammatory cytokines (TNF­α and IL­6) and ROS (p < 0.05). However, these results were reversed by 10/100 µM of vitexin. In addition, vitexin could significantly increase the expression of miR-409 (p < 0.05). Further studies showed that overexpression of miR-409 could significantly promote the effect of vitexin on isoflurane-induced neurotoxicity (p < 0.05). Finally, overexpression miR-409 could significantly increase the expression of p-AMPK/t-AMPK and p-GSK3ß/t-GSK3ß. CONCLUSIONS: Vitexin has protective effects against isoflurane-induced neurotoxicity by targeting miR-409 and the AMPK/GSK3ß pathway.


Assuntos
Anestésicos Inalatórios , Apigenina/farmacologia , Isoflurano/farmacologia , MicroRNAs/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP , Animais , Apoptose/efeitos dos fármacos , Criança , Ensaio de Imunoadsorção Enzimática , Glutationa/sangue , Glicogênio Sintase Quinase 3 beta , Humanos , Interleucina-6/sangue , MicroRNAs/genética , Ratos , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
16.
Zoolog Sci ; 37(1): 42-49, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32068373

RESUMO

For seasonal adaptation, the brown-winged green bug Plautia stali (Hemiptera: Pentatomidae) enters reproductive diapause by suppressing juvenile hormone biosynthesis. Plautia stali myoinhibitory peptides (Plast-MIPs) are known to have allatostatic effects and to suppress juvenile hormone biosynthesis. We examined Plast-MIP-producing neurons in the brain with immunohistochemistry and Fourier transform ion cyclotron resonance mass spectrometry. Rabbit polyclonal antiserum against Plast-MIP revealed immunoreactive cells in seven regions of the brain, including the posterior antennal lobe, basal optic lobe, dorsal anterior protocerebrum, ventrolateral protocerebrum, pars intercerebralis, posterior protocerebrum, and dorsal posterior region to the calyx of the mushroom body, aside from the gnathal ganglion. Anatomical locations of the immunoreactive cells in the pars intercerebralis and dorsal posterior region to the mushroom body calyx partly overlapped with the cell body location stained by retrograde dye fills from the corpus allatum and corpus cardiacum complex. Direct mass spectrometry revealed the molecular ion peaks corresponding to the predictive mass of Plast-MIPs in the pars intercerebralis and the corpus allatum-corpus cardiacum complex. Plast-MIP immunoreactivity in different cell types suggests that Plast-MIPs have different functions in the cephalic ganglia. Considering the anatomical location of neurons projecting to the corpus allatum-corpus cardiacum and results of mass spectrometry, Plast-MIP immunoreactive cells in the pars intercerebralis may play a role in suppressing juvenile hormone biosynthesis.


Assuntos
Encéfalo/metabolismo , Hemípteros/fisiologia , Proteínas de Insetos/metabolismo , Neuropeptídeos/metabolismo , Animais , Diapausa de Inseto/fisiologia , Feminino , Hemípteros/metabolismo , Imuno-Histoquímica , Hormônios Juvenis/biossíntese , Neurônios/metabolismo
17.
Klin Monbl Augenheilkd ; 237(2): 128-132, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32040975

RESUMO

The development of neuroprotective and regenerative therapies in the central nervous system (CNS) poses a major challenge in clinical and basic research. In contrast to the peripheral nervous system, which has a comparatively high intrinsic regenerative capacity, this characteristic is poorly developed in the adult CNS. In this review, some basic growth mechanisms of CNS neurons will be highlighted, as well as factors that prevent successful regeneration after injury. Primarily in the context of glaucoma, preclinical and clinical studies are presented which can improve the understanding of neurodegenerative processes in the optical system and thus provide the basis for current and future therapeutic strategies.


Assuntos
Sistema Nervoso Central , Neuroproteção , Glaucoma , Humanos , Regeneração Nervosa , Neurônios
18.
Science ; 367(6477): 510-511, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32001643
19.
J Neurosci ; 40(5): 944-954, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996470

RESUMO

The brilliant and often prescient hypotheses of Ramon y Cajal have proven foundational for modern neuroscience, but his statement that "In adult centers the nerve paths are something fixed, ended, immutable … " is an exception that did not stand the test of empirical study. Mechanisms of cellular and circuit-level plasticity continue to shape and reshape many regions of the adult nervous system long after the neurodevelopmental period. Initially focused on neurons alone, the field has followed a meteoric trajectory in understanding of activity-regulated neurodevelopment and ongoing neuroplasticity with an arc toward appreciating neuron-glial interactions and the role that each neural cell type plays in shaping adaptable neural circuity. In this review, as part of a celebration of the 50th anniversary of Society for Neuroscience, we provide a historical perspective, following this arc of inquiry from neuronal to neuron-glial mechanisms by which activity and experience modulate circuit structure and function. The scope of this consideration is broad, and it will not be possible to cover the wealth of knowledge about all aspects of activity-dependent circuit development and plasticity in depth.


Assuntos
Encéfalo/metabolismo , Rede Nervosa/metabolismo , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Animais , Encéfalo/citologia , Humanos , Rede Nervosa/citologia
20.
Nature ; 577(7789): 176-177, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31907452

Assuntos
Galáxias , Neurônios
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