Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Filtros adicionais











Tipo de estudo
País/Região como assunto
Intervalo de ano
1.
J Comp Neurol ; 526(16): 2631-2646, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30136724

RESUMO

In the postnatal mammalian brain, neural stem cells of the ventricular-subventricular zone continue to generate doublecortin (Dcx)-expressing immature neurons. Throughout life, these immature neurons migrate to the olfactory bulb through the rostral migratory stream (RMS). In this study, we investigated the distribution of these putative immature neurons using enhanced green fluorescent protein (EGFP) expression in the area surrounding the RMS of the juvenile Dcx-EGFP mice. Through the combined use of an optical clearing reagent (a 2,2'-thiodiethanol solution) and two-photon microscopy, we visualized three-dimensionally the EGFP-positive cells in the entire RMS and its surroundings. The resulting wide-field and high-definition images along with computational image processing methods developed in this study were used to comprehensively determine the position of the EGFP-positive cells. Our findings revealed that the EGFP-positive cells were heterogeneously distributed in the area surrounding the RMS. In addition, the orientation patterns of the leading process of these cells, which displayed the morphology of migrating immature neurons, differed depending on their location. These novel results provide highly precise morphological information for immature neurons and suggest that a portion of immature neurons may be detached from the RMS and migrate in various directions.

2.
J Neurosci ; 38(19): 4598-4609, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29661967

RESUMO

In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss-of-function and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell-cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB.SIGNIFICANCE STATEMENT In the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 (disabled-1) decrease the cell-cell adhesion between chain-forming neuroblasts, which involves adherens junction-like structures. Our results suggest that Fyn-mediated regulation of the cell-cell adhesion of neuroblasts is critical for their detachment from chains in the postnatal brain.

3.
EMBO J ; 37(4)2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29348324

RESUMO

Newborn neurons maintain a very simple, bipolar shape, while they migrate from their birthplace toward their destinations in the brain, where they differentiate into mature neurons with complex dendritic morphologies. Here, we report a mechanism by which the termination of neuronal migration is maintained in the postnatal olfactory bulb (OB). During neuronal deceleration in the OB, newborn neurons transiently extend a protrusion from the proximal part of their leading process in the resting phase, which we refer to as a filopodium-like lateral protrusion (FLP). The FLP formation is induced by PlexinD1 downregulation and local Rac1 activation, which coincide with microtubule reorganization and the pausing of somal translocation. The somal translocation of resting neurons is suppressed by microtubule polymerization within the FLP The timing of neuronal migration termination, controlled by Sema3E-PlexinD1-Rac1 signaling, influences the final positioning, dendritic patterns, and functions of the neurons in the OB These results suggest that PlexinD1 signaling controls FLP formation and the termination of neuronal migration through a precise control of microtubule dynamics.


Assuntos
Movimento Celular , Extensões da Superfície Celular/fisiologia , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurogênese , Neurônios/citologia , Neurônios/fisiologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Glicoproteínas/genética , Glicoproteínas/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
4.
Cell Stem Cell ; 22(1): 128-137.e9, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29276142

RESUMO

Radial glia (RG) are embryonic neural stem cells (NSCs) that produce neuroblasts and provide fibers that act as a scaffold for neuroblast migration during embryonic development. Although they normally disappear soon after birth, here we found that RG fibers can persist in injured neonatal mouse brains and act as a scaffold for postnatal ventricular-subventricular zone (V-SVZ)-derived neuroblasts that migrate to the lesion site. This injury-induced maintenance of RG fibers has a limited time window during post-natal development and promotes directional saltatory movement of neuroblasts via N-cadherin-mediated cell-cell contacts that promote RhoA activation. Transplanting an N-cadherin-containing scaffold into injured neonatal brains likewise promotes migration and maturation of V-SVZ-derived neuroblasts, leading to functional improvements in impaired gait behaviors. Together these results suggest that RG fibers enable postnatal V-SVZ-derived neuroblasts to migrate toward sites of injury, thereby enhancing neuronal regeneration and functional recovery from neonatal brain injuries.

5.
Cell Rep ; 20(4): 960-972, 2017 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-28746879

RESUMO

Motile cilia in ependymal cells, which line the cerebral ventricles, exhibit a coordinated beating motion that drives directional cerebrospinal fluid (CSF) flow and guides neuroblast migration. At the apical cortex of these multi-ciliated cells, asymmetric localization of planar cell polarity (PCP) proteins is required for the planar polarization of microtubule dynamics, which coordinates cilia orientation. Daple is a disheveled-associating protein that controls the non-canonical Wnt signaling pathway and cell motility. Here, we show that Daple-deficient mice present hydrocephalus and their ependymal cilia lack coordinated orientation. Daple regulates microtubule dynamics at the anterior side of ependymal cells, which in turn orients the cilial basal bodies required for the directional cerebrospinal fluid flow. These results demonstrate an important role for Daple in planar polarity in motile cilia and provide a framework for understanding the mechanisms and functions of planar polarization in the ependymal cells.


Assuntos
Proteínas de Transporte/metabolismo , Epêndima/metabolismo , Hidrocefalia/metabolismo , Microtúbulos/metabolismo , Animais , Proteínas de Transporte/genética , Movimento Celular/genética , Movimento Celular/fisiologia , Polaridade Celular/genética , Polaridade Celular/fisiologia , Cílios/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
6.
J Neurochem ; 141(6): 835-847, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28251650

RESUMO

Adult neurogenesis was first observed nearly 60 years ago, and it has since grown into an important neurochemistry research field. Much recent research has focused on the treatment of brain diseases through neuronal regeneration with endogenously generated neurons. In the adult brain, immature neurons called neuroblasts are continuously generated in the ventricular-subventricular zone (V-SVZ). These neuroblasts migrate rapidly through the rostral migratory stream to the olfactory bulb, where they mature and are integrated into the neuronal circuitry. After brain insult, some of the neuroblasts in the V-SVZ migrate toward the lesion to repopulate the injured tissue. This notable migratory capacity of V-SVZ-derived neuroblasts is important for efficiently regenerating neurons in remote areas of the brain. As these neurons migrate for long distances through adult brain tissue, they are supported by various guidance cues and structures that act as scaffolds. Some of these mechanisms are unique to neuroblast migration in the adult brain, and are not involved in migration in the developing brain. Here, we review the latest findings on the mechanisms of neuroblast migration in the adult brain under physiological and pathological conditions, and discuss various issues that still need to be resolved. This article is part of the mini review series "60th Anniversary of the Japanese Society for Neurochemistry".


Assuntos
Encéfalo/crescimento & desenvolvimento , Movimento Celular/fisiologia , Células-Tronco Neurais/citologia , Neurogênese/fisiologia , Neurônios/citologia , Animais , Mapeamento Encefálico , Humanos
7.
Shinrigaku Kenkyu ; 87(2): 198-204, 2016 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-27476271

RESUMO

This study focused on the differences between two, subtypes of envy known as "benign envy" and "malicious envy" as personality traits, and examined the effects of these traits on academic achievement. Two hundred fifty-one university students participated in the study. Both benign envy and malicious envy were found to be independent as also found in a previous study by Lange & Crusius (2015), and a high criterion-related validity was revealed by an association with characteristic variables such as dispositional envy and self-esteem. The students with higher levels of benign envy were found to set goals higher, and as a result achieved higher levels of academic performance. In contrast, no such effect was found for malicious envy. The importance of focusing more attention on the positive aspects of the emotion of envy is discussed.


Assuntos
Logro , Personalidade , Adolescente , Feminino , Humanos , Masculino , Estudantes
8.
Arch Toxicol ; 90(8): 1949-58, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27055686

RESUMO

The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at ≥20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H.


Assuntos
Poluentes Atmosféricos/toxicidade , Hexanóis/toxicidade , Exposição por Inalação/efeitos adversos , Bulbo Olfatório/efeitos dos fármacos , Mucosa Olfatória/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos Endogâmicos ICR , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/imunologia , Bulbo Olfatório/imunologia , Bulbo Olfatório/patologia , Mucosa Olfatória/imunologia , Mucosa Olfatória/patologia , Tamanho do Órgão/efeitos dos fármacos , Fatores de Tempo
9.
J Comp Neurol ; 524(15): 2982-92, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-26991819

RESUMO

In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Envelhecimento/fisiologia , Epêndima/citologia , Nicho de Células-Tronco/fisiologia , Telencéfalo/citologia , Peixe-Zebra/fisiologia , Envelhecimento/patologia , Animais , Animais Geneticamente Modificados , Movimento Celular/fisiologia , Cílios/ultraestrutura , Epêndima/crescimento & desenvolvimento , Epêndima/fisiologia , Epêndima/ultraestrutura , Imuno-Histoquímica , Microscopia Confocal , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Telencéfalo/crescimento & desenvolvimento , Telencéfalo/fisiologia , Telencéfalo/ultraestrutura , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/crescimento & desenvolvimento
10.
Neurochem Res ; 41(1-2): 222-30, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26572545

RESUMO

In many animal species, the production of new neurons (neurogenesis) occurs throughout life, in a specialized germinal region called the ventricular-subventricular zone (V-SVZ). In this region, neural stem cells undergo self-renewal and generate neural progenitor cells and new neurons. In the olfactory system, the new neurons migrate rostrally toward the olfactory bulb, where they differentiate into mature interneurons. V-SVZ-derived new neurons can also migrate toward sites of brain injury, where they contribute to neural regeneration. Recent studies indicate that two major branches of the Wnt signaling pathway, the Wnt/ß-catenin and Wnt/planar cell polarity pathways, play essential roles in various facets of adult neurogenesis. Here, we review the Wnt signaling-mediated regulation of adult neurogenesis in the V-SVZ under physiological and pathological conditions.


Assuntos
Ventrículos Cerebrais/metabolismo , Neurônios/citologia , Transdução de Sinais , Proteínas Wnt/metabolismo , Animais , Diferenciação Celular , Movimento Celular , Polaridade Celular , Proliferação de Células , Camundongos , beta Catenina/metabolismo
11.
Front Cell Neurosci ; 9: 146, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25941474

RESUMO

Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

12.
Tissue Eng Part A ; 21(1-2): 193-201, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25010638

RESUMO

After brain injury, neuroblasts generated from endogenous neural stem cells migrate toward the injured site using blood vessels as a scaffold, raising the possibility of reconstructing blood vessel network scaffolds as a strategy for promoting endogenous neuronal regeneration. In this study, we designed biomaterials based on the components and morphology of blood vessel scaffolds, and examined their ability to guide the migration of neuroblasts into a brain lesion site in mice. Transplanted porous sponge containing components of the basement membrane (BM) matrix enhanced neuroblast migration into the lesion, and detailed morphological examination suggested that the infiltrating cells used the BM sponge as a migration scaffold. Laminin (LN)-rich porous sponge also enhanced the migration of neuroblasts into the lesion, whereas BM gel and gelatin porous sponge did not. We conclude that the transplantation of LN-rich porous sponge promotes neuroblast migration into cortical lesions. This study highlights the possibility of using artificial blood vessel scaffolds to promote the regeneration of injured cerebral cortex.


Assuntos
Movimento Celular/efeitos dos fármacos , Córtex Cerebral/patologia , Laminina/farmacologia , Neurônios/citologia , Tecidos Suporte/química , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Membrana Basal/química , Camundongos Endogâmicos ICR , Microglia/citologia , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Poríferos , Porosidade
13.
Nat Commun ; 5: 4532, 2014 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-25074242

RESUMO

Throughout life, new neurons generated in the ventricular-subventricular zone take the long journey to the olfactory bulb. The intracellular mechanisms that precisely control the neurons' migration speed, enabling their well-organized movement, remain unclear. Rho signalling is known to affect the morphology and movement of various cell types, including neurons. Here we identify Gem-interacting protein (Gmip), a RhoA-specific GTPase-activating protein, as a key factor in saltatory neuronal migration. RhoA is activated at the proximal leading process of migrating neurons, where Gmip is also localized and negatively regulates RhoA. Gmip controls the saltatory movement of neurons that regulate their migration speed and 'stop' positions in the olfactory bulb, thereby altering the neural circuitry. This study demonstrates that Gmip serves as a brake for the RhoA-mediated movement of neuronal somata, and highlights the significance of speed control in the well-organized neuronal migration and the maintenance of neuronal circuits in the postnatal brain.


Assuntos
Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Movimento Celular/fisiologia , Proteínas Ativadoras de GTPase/metabolismo , Neurônios/fisiologia , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Western Blotting , Bromodesoxiuridina , Imuno-Histoquímica , Imunoprecipitação , Espectrometria de Massas , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Microscopia Confocal , Interferência de RNA , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Imagem com Lapso de Tempo , Proteínas de Transporte Vesicular/metabolismo
14.
Front Neurosci ; 8: 53, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24672424

RESUMO

Neural stem cells in the mammalian adult brain continuously produce new neurons throughout life. Accumulating evidence in rodents suggests that various aspects of adult neurogenesis, including the genesis, migration, and maturation of new neurons, are regulated by factors derived from blood vessels and their microenvironment. Brain injury enhances both neurogenesis and angiogenesis, thereby promoting the cooperative regeneration of neurons and blood vessels. In this paper, we briefly review the mechanisms for the vascular regulation of adult neurogenesis in the ventricular-subventricular zone under physiological and pathological conditions, and discuss their clinical potential for brain regeneration strategies.

15.
J Neurochem ; 128(6): 790-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24188721

RESUMO

New neurons generated in the ventricular-subventricular zone in the post-natal brain travel toward the olfactory bulb by using a collective cell migration process called 'chain migration.' These new neurons show a saltatory movement of their soma, suggesting that each neuron cycles through periods of 'rest' during migration. Here, we investigated the role of the resting neurons in chain migration using post-natal mouse brain, and found that they undergo a dynamic morphological change, in which a deep indentation forms in the cell body. Inhibition of Rac1 activity resulted in less indentation of the new neurons in vivo. Live cell imaging using a Förster resonance energy transfer biosensor revealed that Rac1 was activated at the sites of contact between actively migrating and resting new neurons. On the cell surface of resting neurons, Rac1 activation coincided with the formation of the indentation. Furthermore, Rac1 knockdown prevented the indentation from forming and impaired migration along the resting neurons. These results suggest that Rac1 regulates a morphological change in the resting neurons, which allows them to serve as a migratory scaffold, and thereby non-cell-autonomously promotes chain migration.


Assuntos
Comunicação Celular/fisiologia , Movimento Celular/fisiologia , Ventrículos Cerebrais/citologia , Neurônios/fisiologia , Neuropeptídeos/fisiologia , Bulbo Olfatório/citologia , Proteínas rac1 de Ligação ao GTP/fisiologia , Animais , Ventrículos Cerebrais/crescimento & desenvolvimento , Camundongos , Neurogênese/fisiologia , Bulbo Olfatório/crescimento & desenvolvimento , Técnicas de Cultura de Órgãos , Imagem com Lapso de Tempo
16.
Keio J Med ; 62(1): 13-28, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23563788

RESUMO

Even in the adult brain, new neurons are continuously generated from endogenous neural stem cells that reside in two restricted regions: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus. These new neurons are integrated into the mature neuronal circuitry and become involved in various functions, thereby contributing to structural and functional plasticity in the adult brain. In this review, we summarize our recent findings on the regulatory mechanisms of SVZ neurogenesis under physiological and pathological conditions in various animal models. Some of these findings were presented in the Kitazato Prize Lecture at Keio University School of Medicine in 2011.


Assuntos
Giro Denteado/fisiologia , Ventrículos Laterais/fisiologia , Células-Tronco Neurais/citologia , Neurogênese , Neurônios/citologia , Adulto , Animais , Diferenciação Celular , Movimento Celular , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Giro Denteado/lesões , Giro Denteado/fisiopatologia , Regulação da Expressão Gênica , Humanos , Ventrículos Laterais/lesões , Ventrículos Laterais/fisiopatologia , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Recuperação de Função Fisiológica , Via de Sinalização Wnt
17.
J Antibiot (Tokyo) ; 66(3): 165-70, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23361358

RESUMO

In the course of screening for an inhibitor of farnesyl transferase (FTase), we identified two compounds, N-benzyl-aclacinomycin A (ACM) and N-allyl-ACM, which are new derivatives of ACM. N-benzyl-ACM and N-allyl-ACM inhibited FTase activity with IC50 values of 0.86 and 2.93 µM, respectively. Not only ACM but also C-10 epimers of each ACM derivative failed to inhibit FTase. The inhibition of FTase by N-benzyl-ACM and N-allyl-ACM seems to be specific, because these two compounds did not inhibit geranylgeranyltransferase or geranylgeranyl pyrophosphate (GGPP) synthase up to 100 µM. In cultured A431 cells, N-benzyl-ACM and N-allyl-ACM also blocked both the membrane localization of H-Ras and activation of the H-Ras-dependent PI3K/Akt pathway. In addition, they inhibited epidermal growth factor (EGF)-induced migration of A431 cells. Thus, N-benzyl-ACM and N-allyl-ACM inhibited EGF-induced migration of A431 cells by inhibiting the farnesylation of H-Ras and subsequent H-Ras-dependent activation of the PI3K/Akt pathway.


Assuntos
Aclarubicina/análogos & derivados , Aclarubicina/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Farnesiltranstransferase/antagonistas & inibidores , Aclarubicina/administração & dosagem , Alquil e Aril Transferases/efeitos dos fármacos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Fator de Crescimento Epidérmico/administração & dosagem , Genes ras/efeitos dos fármacos , Geranil-Geranildifosfato Geranil-Geraniltransferase/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
18.
PLoS One ; 7(11): e48431, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23133633

RESUMO

Sensory input is essential for the normal development of sensory centers in the brain, such as the somatosensory, visual, auditory, and olfactory systems. Visual deprivation during a specific developmental stage, called the critical period, results in severe and irreversible functional impairments in the primary visual cortex. Olfactory deprivation in the early postnatal period also causes significant developmental defects in the olfactory bulb, the primary center for olfaction. Olfactory bulb interneurons are continuously generated from neural stem cells in the ventricular-subventricular zone, suggesting that the olfactory system has plasticity even in adulthood. Here, we investigated the effect of transient neonatal olfactory deprivation on the addition of interneurons to the glomerular layer of the adult mouse olfactory bulb. We found that the addition of one subtype of interneurons was persistently inhibited even after reopening the naris. BrdU pulse-chase experiments revealed that the neonatal olfactory deprivation predominantly affected an early phase in the maturation of this neuronal subtype in the olfactory bulb. Subjecting the mice to odor stimulation for 6 weeks after naris reopening resulted in significant recovery from the histological and functional defects caused by the olfactory deprivation. These results suggest that a subtype-specific critical period exists for olfactory bulb neurogenesis, but that this period is less strict and more plastic compared with the critical periods for other systems. This study provides new insights into the mechanisms of postnatal neurogenesis and a biological basis for the therapeutic effect of olfactory training.


Assuntos
Neurogênese/fisiologia , Bulbo Olfatório/patologia , Olfato/fisiologia , Animais , Bromodesoxiuridina/farmacologia , Núcleo Celular/metabolismo , Imuno-Histoquímica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Odorantes , Privação Sensorial/fisiologia , Córtex Visual/fisiologia
19.
Psychol Rep ; 111(1): 322-34, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23045875

RESUMO

The aim of this study was to construct a model of the elicitation of schadenfreude through vengeance, envy, and trait anger. Japanese undergraduates (239 men, 284 women) completed questionnaires assessing dispositional vengeance, trait anger, and empathy. Then, participants read two scenarios: one about a target person's success and one about his or her misfortune. After reading the first scenario, the participants were asked to rate their envy toward the target person, then their feelings of schadenfreude after the second. A Japanese version of the Vengeance Scale was developed, and its construct validity and test-retest reliability were confirmed. Structural equation modeling was applied to examine how dispositional vengeance, trait anger, and envy were related to schadenfreude. The results indicated that envy and dispositional vengeance were significantly related to scores on the schadenfreude scale, with no gender effect, whereas vengeance was associated with envy only for women.


Assuntos
Agressão/psicologia , Ira , Caráter , Hostilidade , Ciúmes , Adolescente , Empatia , Feminino , Humanos , Japão , Masculino , Teoria da Construção Pessoal , Inventário de Personalidade , Autoimagem , Fatores Sexuais , Desejabilidade Social , Adulto Jovem
20.
Stem Cells Int ; 2012: 915160, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23093979

RESUMO

Recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain. Some of these new neurons migrate to injured brain tissues and differentiate into mature neurons, suggesting that such new neurons may be able to replace neurons lost to degenerative disease or injury and improve or repair neurological deficits. Here, we tested whether delivering growth factors via gelatin hydrogel microspheres would support neurogenesis in the SVZ. Insulin-like growth factor-1 (IGF-1)-containing microspheres increased the number of new neurons in the SVZ. Hepatocyte growth factor (HGF)-containing microspheres increased the number of new neurons migrating from the SVZ towards the injured striatum in a stroke model in mouse. These results suggest that the strategy of using gelatin hydrogel microspheres to achieve the sustained release of growth factors holds promise for the clinical regeneration of damaged brain tissues from endogenous neural stem cells in the adult SVZ.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA