Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nat Commun ; 14(1): 6499, 2023 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-37838794

RESUMO

Previous work has shown that motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursor cells (OLPs) in the brains of adult mice. In the present study we ask whether OL production is also required for non-motor learning and cognition, using T-maze and radial-arm-maze tasks that tax spatial working memory. We find that maze training stimulates OLP proliferation and OL production in the medial prefrontal cortex (mPFC), anterior corpus callosum (genu), dorsal thalamus and hippocampal formation of adult male mice; myelin sheath formation is also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional-knockout mice strongly impairs training-induced improvements in maze performance. We find a strong positive correlation between the performance of individual wild type mice and the scale of OLP proliferation and OL generation during training, but not with the number or intensity of c-Fos+ neurons in their mPFC, underscoring the important role played by OL lineage cells in cognitive processing.


Assuntos
Treino Cognitivo , Memória de Curto Prazo , Humanos , Camundongos , Animais , Masculino , Oligodendroglia , Camundongos Knockout , Cognição , Bainha de Mielina/fisiologia
2.
FASEB J ; 34(1): 1465-1480, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914590

RESUMO

Cardiolipin (CL) is a hallmark phospholipid of mitochondria and plays a significant role in maintaining the mitochondrial structure and functions. Despite the physiological importance of CL, mutant organisms, yeast, Arabidopsis, C elegans, and Drosophila, which lack CL synthase (Crls1) gene and consequently are deprived of CL, are viable. Here we report conditional Crls1-deficient mice using targeted insertion of loxP sequences flanking the functional domain of CRLS1 enzyme. Homozygous null mutant mice exhibited early embryonic lethality at the peri-implantation stage. We generated neuron-specific Crls1 knockout (cKO) mice by crossing with Camk2α-Cre mice. Neuronal loss and gliosis were gradually manifested in the forebrains, where CL levels were significantly decreased. In the surviving neurons, malformed mitochondria with bubble-like or onion-like inner membrane structures were observed. We showed decreased supercomplex assembly and reduced enzymatic activities of electron transport chain complexes in the forebrain of cKO mice, resulting in affected mitochondrial calcium dynamics, a slower rate of Ca2+ uptake and a smaller calcium retention capacity. These observations clearly demonstrate indispensable roles of CL as well as of Crls1 gene in mammals.


Assuntos
Sinalização do Cálcio , Cardiolipinas/metabolismo , Embrião de Mamíferos/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Prosencéfalo/embriologia , Animais , Cálcio/metabolismo , Cardiolipinas/genética , Embrião de Mamíferos/patologia , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/patologia , Neurônios/patologia , Prosencéfalo/patologia , Transferases (Outros Grupos de Fosfato Substituídos)/deficiência , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
3.
J Neurochem ; 148(3): 413-425, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30152001

RESUMO

Multiple sclerosis (MS) is an autoimmune disease characterized by immune-mediated inflammation, which attacks the myelin sheath. MS pursues a relapsing and remitting course with varying intervals between symptoms. The main clinical pathological features include inflammation, myelin sheath destruction and plaque formation in the central nervous system (CNS). We previously reported that cystatin F (CysF) expression is induced in demyelinating lesions that are accompanied by active remyelination (referred to as shadow plaques) but is down-regulated in chronic demyelinated lesions (plaques) in the spinal cord of MS patients and in several murine models of demyelinating disease. CysF is a cathepsin protease inhibitor whose major target is cathepsin C (CatC), which is co-expressed in demyelinating regions in Plp4e/- mice, a model of chronic demyelination. Here, we report the time course of CatC and CysF expression and describe the symptoms in a mouse experimental autoimmune encephalomyelitis (EAE) model using CatC knockdown (KD) and CatC over-expression (OE) mice. In myelin oligodendrocyte glycoprotein (MOG)-EAE, CatC positive cells were found to infiltrate the CNS at an early stage prior to any clinical signs, in comparison to WT mice. CysF expression was not observed at this early stage, but appeared later within shadow plaques. CatC expression was found in chronic demyelinated lesions but was not associated with CysF expression, and CatCKD EAE mouse showed delayed demyelination. Whereas, CatCOE in microglia significantly increased severity of demyelination in the MOG-EAE model. Thus, these results demonstrate that CatC plays a major role in MOG-EAE.


Assuntos
Encéfalo/metabolismo , Catepsina C/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Degeneração Neural/metabolismo , Medula Espinal/metabolismo , Animais , Encéfalo/patologia , Cistatinas/metabolismo , Encefalomielite Autoimune Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Glicoproteína Mielina-Oligodendrócito/imunologia , Degeneração Neural/patologia , Medula Espinal/patologia
4.
Sci Rep ; 8(1): 6701, 2018 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-29712939

RESUMO

Secretory lysosomes are required for the specialised functions of various types of differentiated cells. In osteoclasts, the lysosomal proton pump V-ATPase (vacuolar-type ATPase) is targeted to the plasma membrane via secretory lysosomes and subsequently acidifies the extracellular compartment, providing optimal conditions for bone resorption. However, little is known about the mechanism underlying this trafficking of secretory lysosomes. Here, we demonstrate that the lysosome-specific a3 isoform of the V-ATPase a subunit plays an indispensable role in secretory lysosome trafficking, together with Rab7, a small GTPase involved in organelle trafficking. In osteoclasts lacking a3, lysosomes were not transported to the cell periphery, and Rab7 was not localised to lysosomes but diffused throughout the cytoplasm. Expression of dominant-negative (GDP-bound form) Rab7 inhibited lysosome trafficking in wild-type cells. Furthermore, a3 directly interacted with the GDP-bound forms of Rab7 and Rab27A. These findings reveal a novel role for the proton pump V-ATPase in secretory lysosome trafficking and an unexpected mechanistic link with Rab GTPases.


Assuntos
Lisossomos/genética , ATPases Vacuolares Próton-Translocadoras/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab27 de Ligação ao GTP/genética , Animais , Citoplasma/genética , Regulação Enzimológica da Expressão Gênica , Guanosina Difosfato/genética , Humanos , Lisossomos/enzimologia , Camundongos , Camundongos Knockout , Organelas/genética , Isoformas de Proteínas/genética , Transporte Proteico/genética , proteínas de unión al GTP Rab7
5.
Neurosci Res ; 136: 33-47, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29481883

RESUMO

GPRC5B is a membrane glycoprotein robustly expressed in mouse cerebellar Purkinje cells (PCs). Its function is unknown. In Gprc5b-/- mice that lack GPRC5B, PCs develop distal axonal swellings in deep cerebellar nuclei (DCN). Numerous misshapen mitochondria, which generated excessive amounts of reactive oxygen species (ROS), accumulated in these distal axonal swellings. In primary cell cultures of Gprc5b-/- PCs, pharmacological reduction of ROS prevented the appearance of such swellings. To examine the physiological role of GPRC5B in PCs, we analyzed cerebellar synaptic transmission and cerebellum-dependent motor learning in Gprc5b-/- mice. Patch-clamp recordings in cerebellum slices in vitro revealed that the induction of long-term depression (LTD) at parallel fiber-PC synapses was normal in adult Gprc5b-/- mice, whereas the induction of long-term potentiation (LTP) at mossy fiber-DCN neuron synapses was attenuated in juvenile Gprc5b-/- mice. In Gprc5b-/- mice, long-term motor learning was impaired in both the rotarod test and the horizontal optokinetic response eye movement (HOKR) test. These observations suggest that GPRC5B plays not only an important role in the development of distal axons of PCs and formation of synapses with DCN neurons, but also in the synaptic plasticity that underlies long-term motor learning.


Assuntos
Cerebelo/fisiologia , Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Células de Purkinje/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Depressão Sináptica de Longo Prazo/fisiologia , Camundongos Transgênicos , Receptores Acoplados a Proteínas G/deficiência , Sinapses/genética
6.
Elife ; 62017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28608780

RESUMO

Myelin, made by oligodendrocytes, is essential for rapid information transfer in the central nervous system. Oligodendrocyte precursors (OPs) receive glutamatergic synaptic input from axons but how this affects their development is unclear. Murine OPs in white matter express AMPA receptor (AMPAR) subunits GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, which respectively reduced or abolished AMPAR-mediated input to OPs. In both double- and triple-knockouts OP proliferation and number were unchanged but ~25% fewer oligodendrocytes survived in the subcortical white matter during development. In triple knockouts, this shortfall persisted into adulthood. The oligodendrocyte deficit resulted in ~20% fewer myelin sheaths but the average length, number and thickness of myelin internodes made by individual oligodendrocytes appeared normal. Thus, AMPAR-mediated signalling from active axons stimulates myelin production in developing white matter by enhancing oligodendrocyte survival, without influencing myelin synthesis per se.


Assuntos
Bainha de Mielina/metabolismo , Células Precursoras de Oligodendrócitos/fisiologia , Receptores de AMPA/metabolismo , Animais , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Camundongos , Camundongos Knockout , Receptores de AMPA/genética
7.
Glia ; 65(6): 917-930, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28251676

RESUMO

In demyelinating diseases such as multiple sclerosis (MS), an imbalance between the demyelination and remyelination rates underlies the degenerative processes. Microglial activation is observed in demyelinating lesions; however, the molecular mechanism responsible for the homeostatic/environmental change remains elusive. We previously found that cystatin F (CysF), a cysteine protease inhibitor, is selectively expressed in microglia only in actively demyelinating/remyelinating lesions but ceases expression in chronic lesions, suggesting its role in remyelination. Here, we report the effects of manipulating the expression of CysF and cathepsin C (CatC), a key target of CysF, in a murine model of transgenic demyelinating disease, Plp4e/- . During the active remyelinating phase, both CysF knockdown (CysFKD) and microglial-selective CatC overexpression (CatCOE) showed a worsening of the demyelination in Plp4e/- transgenic mice. Conversely, during the chronic demyelinating phase, CatC knockdown (CatCKD) ameliorated the demyelination. Our results suggest that the balance between CatC and CysF expression controls the demyelination and remyelination process.


Assuntos
Encéfalo/metabolismo , Catepsina C/metabolismo , Cistatinas/metabolismo , Doenças Desmielinizantes/metabolismo , Bainha de Mielina/metabolismo , Animais , Encéfalo/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Catepsina C/genética , Células Cultivadas , Cistatinas/genética , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Progressão da Doença , Marcação de Genes , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Microglia/patologia , Proteína Proteolipídica de Mielina/genética , Proteína Proteolipídica de Mielina/metabolismo , Bainha de Mielina/patologia , RNA Mensageiro/metabolismo
8.
Elife ; 62017 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-28130923

RESUMO

Myelination speeds conduction of the nerve impulse, enhancing cognitive power. Changes of white matter structure contribute to learning, and are often assumed to reflect an altered number of myelin wraps. We now show that, in rat optic nerve and cerebral cortical axons, the node of Ranvier length varies over a 4.4-fold and 8.7-fold range respectively and that variation of the node length is much less along axons than between axons. Modelling predicts that these node length differences will alter conduction speed by ~20%, similar to the changes produced by altering the number of myelin wraps or the internode length. For a given change of conduction speed, the membrane area change needed at the node is >270-fold less than that needed in the myelin sheath. Thus, axon-specific adjustment of node of Ranvier length is potentially an energy-efficient and rapid mechanism for tuning the arrival time of information in the CNS.


Assuntos
Axônios/fisiologia , Condução Nervosa , Nós Neurofibrosos/fisiologia , Animais , Bioestatística , Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Modelos Biológicos , Nervo Óptico/citologia , Nervo Óptico/fisiologia , Ratos
9.
Glia ; 65(1): 150-168, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27748972

RESUMO

Astrocytes have recently been shown to provide physiological support for various brain functions, although little is known about their involvement in white matter integrity. Several inherited infantile-onset leukoencephalopathies, such as Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts (MLC), implicate astrocytic involvement in the formation of white matter. Several mouse models of MLC had been generated by knocking out the Mlc1 gene; however, none of those models was reported to show myelin abnormalities prior to formation of the myelin sheath. Here we generated a new Mlc1 knockout mouse and a Mlc1 overexpressing mouse, and demonstrate that astrocyte-specific Mlc1 overexpression causes infantile-onset abnormalities of the white matter in which astrocytic swelling followed by myelin membrane splitting are present, whereas knocking out Mlc1 does not, and only shows myelin abnormalities after 12 months of age. Biochemical analyses demonstrated that MLC1 interacts with the Na+ /K+ ATPase and that overexpression of Mlc1 results in decreased activity of the astrocytic Na+ /K+ pump. In contrast, no changes in Na+ /K+ pump activity were observed in Mlc1 KO mice, suggesting that the reduction in Na+ /K+ pump activity resulting from Mlc1 overexpression causes astrocytic swelling. Our infantile-onset leukoencephalopathy model based on Mlc1 overexpression may provide an opportunity to further explore the roles of astrocytes in white matter development and structural integrity. We established a novel mouse model for infantile-onset leukoencephalopathy by the overexpression of Mlc1. Mlc1 overexpression reduced activity of the astrocytic sodium pump, which may underlie white matter edema followed by myelin membrane splitting. GLIA 2016 GLIA 2017;65:150-168.


Assuntos
Astrócitos/metabolismo , Cistos/metabolismo , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/metabolismo , Proteínas de Membrana/genética , Substância Branca/metabolismo , Animais , Membrana Celular/metabolismo , Cistos/genética , Modelos Animais de Doenças , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Proteínas de Membrana/deficiência , Proteínas de Membrana/metabolismo , Camundongos Transgênicos , Mutação/genética
10.
PLoS One ; 11(11): e0166732, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27855200

RESUMO

Opalin, a central nervous system-specific myelin protein phylogenetically unique to mammals, has been suggested to play a role in mammalian-specific myelin. To elucidate the role of Opalin in mammalian myelin, we disrupted the Opalin gene in mice and analyzed the impacts on myelination and behavior. Opalin-knockout (Opalin-/-) mice were born at a Mendelian ratio and had a normal body shape and weight. Interestingly, Opalin-/- mice had no obvious abnormalities in major myelin protein compositions, expression of oligodendrocyte lineage markers, or domain organization of myelinated axons compared with WT mice (Opalin+/+) mice. Electron microscopic observation of the optic nerves did not reveal obvious differences between Opalin+/+ and Opalin-/- mice in terms of fine structures of paranodal loops, transverse bands, and multi-lamellae of myelinated axons. Moreover, sensory reflex, circadian rhythm, and locomotor activity in the home cage, as well as depression-like behavior, in the Opalin-/- mice were indistinguishable from the Opalin+/+ mice. Nevertheless, a subtle but significant impact on exploratory activity became apparent in Opalin-/- mice exposed to a novel environment. These results suggest that Opalin is not critical for central nervous system myelination or basic sensory and motor activities under conventional breeding conditions, although it might be required for fine-tuning of exploratory behavior.


Assuntos
Comportamento Animal , Mamíferos/metabolismo , Proteínas da Mielina/metabolismo , Bainha de Mielina/metabolismo , Animais , Astrócitos/metabolismo , Axônios/metabolismo , Axônios/ultraestrutura , Peso Corporal , Encéfalo/metabolismo , Comunicação Celular , Diferenciação Celular , Comportamento Exploratório , Immunoblotting , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Proteínas da Mielina/deficiência , Bainha de Mielina/ultraestrutura , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Nervo Óptico/metabolismo , Nervo Óptico/ultraestrutura , Fenótipo , Especificidade da Espécie
11.
Science ; 346(6207): 318-22, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25324381

RESUMO

Myelin-forming oligodendrocytes (OLs) are formed continuously in the healthy adult brain. In this work, we study the function of these late-forming cells and the myelin they produce. Learning a new motor skill (such as juggling) alters the structure of the brain's white matter, which contains many OLs, suggesting that late-born OLs might contribute to motor learning. Consistent with this idea, we show that production of newly formed OLs is briefly accelerated in mice that learn a new skill (running on a "complex wheel" with irregularly spaced rungs). By genetically manipulating the transcription factor myelin regulatory factor in OL precursors, we blocked production of new OLs during adulthood without affecting preexisting OLs or myelin. This prevented the mice from mastering the complex wheel. Thus, generation of new OLs and myelin is important for learning motor skills.


Assuntos
Encéfalo/citologia , Proliferação de Células , Aprendizagem , Destreza Motora/fisiologia , Bainha de Mielina/metabolismo , Oligodendroglia/fisiologia , Animais , Encéfalo/metabolismo , Deleção de Genes , Humanos , Masculino , Rememoração Mental , Camundongos , Camundongos Transgênicos , Bainha de Mielina/genética , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Transmissão Sináptica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
Thromb Haemost ; 112(4): 743-56, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24965909

RESUMO

Megakaryocytes (MKs) generate platelets via intravascular protrusions termed proplatelets, which are tandem arrays of platelet-sized swellings with a beaded appearance. However, it remains unclear whether all intravascular protrusions in fact become proplatelets, and whether MKs generate platelets without forming proplatelets. Here, we visualised the sequential phases of intravascular MK protrusions and fragments in living mouse bone marrow (BM), using intravital microscopy, and examined their ultrastructure. The formation of intravascular protrusions was observed to be a highly dynamic process, in which the size and shape of the protrusions changed sequentially prior to the release of platelet progenitors. Among these intravascular protrusions, immature thick protrusions were distinguished from proplatelets by their size and the dynamic morphogenesis seen by time-lapse observation. In ultrastructural analyses, the thick protrusions and their fragments were characterised by a peripheral zone, abundant endoplasmic reticulum and demarcation membrane system, and random microtubule arrays. Proplatelets were predominant among BM sinusoids in the physiological state; however, during an acute thrombocytopenic period, thick protrusions increased markedly in the sinusoids. These results strongly suggested that BM MKs form and release two types of platelet progenitors via distinct intravascular protrusions, and that platelet demand modulates the type of intravascular protrusion that is formed in vivo.


Assuntos
Plaquetas/citologia , Medula Óssea/fisiologia , Megacariócitos/citologia , Animais , Retículo Endoplasmático/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Microtúbulos/metabolismo , Fótons , Inibidores da Agregação Plaquetária/química , Contagem de Plaquetas , Células-Tronco/citologia , Trombocitopenia/sangue , Trombocitopenia/imunologia , Trombopoese/fisiologia
13.
Cell Host Microbe ; 15(5): 551-63, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24832450

RESUMO

Cerebral malaria is a complication of Plasmodium falciparum infection characterized by sudden coma, death, or neurodisability. Studies using a mouse model of experimental cerebral malaria (ECM) have indicated that blood-brain barrier disruption and CD8 T cell recruitment contribute to disease, but the spatiotemporal mechanisms are poorly understood. We show by ultra-high-field MRI and multiphoton microscopy that the olfactory bulb is physically and functionally damaged (loss of smell) by Plasmodium parasites during ECM. The trabecular small capillaries comprising the olfactory bulb show parasite accumulation and cell occlusion followed by microbleeding, events associated with high fever and cytokine storm. Specifically, the olfactory upregulates chemokine CCL21, and loss or functional blockade of its receptors CCR7 and CXCR3 results in decreased CD8 T cell activation and recruitment, respectively, as well as prolonged survival. Thus, early detection of olfaction loss and blockade of pathological cell recruitment may offer potential therapeutic strategies for ECM.


Assuntos
Malária Cerebral/parasitologia , Bulbo Olfatório/parasitologia , Plasmodium falciparum/fisiologia , Animais , Linfócitos T CD8-Positivos/imunologia , Quimiocina CCL21/genética , Quimiocina CCL21/imunologia , Feminino , Humanos , Malária Cerebral/genética , Malária Cerebral/imunologia , Malária Cerebral/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Bulbo Olfatório/imunologia , Bulbo Olfatório/patologia , Plasmodium falciparum/patogenicidade , Receptores CCR7/genética , Receptores CCR7/imunologia , Receptores CXCR3/genética , Receptores CXCR3/imunologia , Virulência
14.
Psychopharmacology (Berl) ; 231(1): 221-30, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23949207

RESUMO

RATIONALE AND OBJECTIVES: The effects of low thyroid hormone level during embryogenesis on MRI of the brain and social behaviors of hatchlings were examined using "fertilized hen's egg-embryo-chick" system. METHODS AND RESULTS: Control and hatchlings treated with methimazole (20 µmol/egg), which hatched 3 days later than controls were examined. The results are as follows: 1. The MRI examination of the midsagittal section of the brain on hatch day showed that the sizes, by T1- and ADC values by diffusion-weighted images, of the optic lobe and cerebellum of the MMI-hatchlings were significantly bigger than those of the controls. 2. The social behaviors on post-hatch day 3 were based on the following tests: (a) Aggregation test: The speed of four chicks, individually isolated by cardboard barriers in a box, to make a group upon the removal of barriers. (b) Belongingness tests: The speed of a chick isolated at a corner to join the group of three chicks placed at the opposite corner. (c) Vocalization test: The number of decibel produced by a chick isolated at a corner using a sound meter. These tests demonstrated that MMI-hatchlings took longer times and had weaker vocalization than the controls, significantly. 3. Upregulation of THRß mRNA after MMI treatment suggested that THR was necessary for cerebellum development. CONCLUSIONS: The MMI exposure during the last week of embryogenesis possibly delayed the myelination of certain brain regions and impaired the social behaviors of hatchlings. The chick embryos can be easily induced with hypothyroidism without maternal influences, and the hatchling's behaviors were analyzed using a video camera. The present method will be useful for assessing the effects of unfavorable influences during embryogenesis on social behaviors in later life.


Assuntos
Antitireóideos/farmacologia , Química Encefálica/fisiologia , Encéfalo/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Metimazol/farmacologia , RNA Mensageiro/biossíntese , Comportamento Social , Receptores beta dos Hormônios Tireóideos/biossíntese , Animais , Animais Recém-Nascidos , Ansiedade de Separação/psicologia , Encéfalo/anatomia & histologia , Encéfalo/embriologia , Química Encefálica/efeitos dos fármacos , Cerebelo/anatomia & histologia , Cerebelo/embriologia , Embrião de Galinha , Galinhas , Imagem de Difusão por Ressonância Magnética , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Equilíbrio Postural/efeitos dos fármacos , RNA Mensageiro/genética , Receptores beta dos Hormônios Tireóideos/genética , Tri-Iodotironina/fisiologia , Regulação para Cima/efeitos dos fármacos , Vocalização Animal
15.
Neuron ; 77(5): 873-85, 2013 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-23473318

RESUMO

Oligodendrocyte precursors (OPs) continue to proliferate and generate myelinating oligodendrocytes (OLs) well into adulthood. It is not known whether adult-born OLs ensheath previously unmyelinated axons or remodel existing myelin. We quantified OP division and OL production in different regions of the adult mouse CNS including the 4-month-old optic nerve, in which practically all axons are already myelinated. Even there, all OPs were dividing and generating new OLs and myelin at a rate higher than can be explained by first-time myelination of naked axons. We conclude that adult-born OLs in the optic nerve are engaged in myelin remodeling, either replacing OLs that die in service or intercalating among existing myelin sheaths. The latter would predict that average internode length should decrease with age. Consistent with that, we found that adult-born OLs elaborated much shorter but many more internodes than OLs generated during early postnatal life.


Assuntos
Sistema Nervoso Central/fisiologia , Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia , Envelhecimento/fisiologia , Animais , Contagem de Células , Ciclo Celular , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Sobrevivência Celular/fisiologia , Sistema Nervoso Central/crescimento & desenvolvimento , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Microscopia Imunoeletrônica , Bainha de Mielina/ultraestrutura , Oligodendroglia/ultraestrutura , Nervo Óptico/citologia , Nervo Óptico/crescimento & desenvolvimento , Nervo Óptico/fisiologia , Reação em Cadeia da Polimerase , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética
16.
J Comp Neurol ; 521(1): 203-12, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22700307

RESUMO

Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to propagate via neural circuits to the central nervous system after peripheral inoculation, resulting in acute deadly encephalomyelitis in natural host piglets as well as in experimental younger rodents. This study has systematically examined the assembly and dissemination of HEV 67N in the primary motor cortex of infected rats and provides additional evidence indicating that membranous-coating-mediated endo-/exocytosis can be used by HEV for its transsynaptic transfer. In addition, our results suggested that this transsynaptic pathway could adapted for larger granular materials, such as viruses. These findings should help in understanding the mechanisms underlying coronavirus infections as well as the intercellular exchanges occurring at the synaptic junctions.


Assuntos
Sistema Nervoso Central/patologia , Infecções por Coronavirus/patologia , Coronavirus/metabolismo , Neurônios/patologia , Sinapses/patologia , Proteínas da Matriz Viral/metabolismo , Animais , Linhagem Celular Transformada , Sistema Nervoso Central/ultraestrutura , Vesículas Revestidas/patologia , Vesículas Revestidas/ultraestrutura , Vesículas Revestidas/virologia , Modelos Animais de Doenças , Masculino , Neurônios/ultraestrutura , Neurônios/virologia , Transporte Proteico/fisiologia , Ratos , Ratos Wistar , Suínos , Sinapses/ultraestrutura , Sinapses/virologia
17.
Microscopy (Oxf) ; 62(2): 317-20, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23081991

RESUMO

To evaluate the advantages of combination of two advanced electron microscopic technologies such as serial block-face scanning electron microscopy and double-axis electron beam tomography, we analyzed the three-dimensional morphology of cellular relationships between dendritic and plasma cells in the synovial membrane from patients with rheumatoid arthritis, using the combined approach.


Assuntos
Artrite Reumatoide/patologia , Células Dendríticas/ultraestrutura , Plasmócitos/ultraestrutura , Membrana Sinovial/ultraestrutura , Comunicação Celular , Células Dendríticas/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Microscopia Eletrônica de Varredura , Plasmócitos/fisiologia , Tomografia Computadorizada por Raios X
18.
Glia ; 58(10): 1197-207, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20544855

RESUMO

Glycosphingolipids (GSLs) occur in all mammalian plasma membranes. They are most abundant in neuronal cells and have essential roles in brain development. Glucosylceramide (GlcCer) synthase, which is encoded by the Ugcg gene, is the key enzyme driving the synthesis of most neuronal GSLs. Experiments using conditional Nestin-Cre Ugcg knockout mice have shown that GSL synthesis in vivo is essential, especially for brain maturation. However, the roles of GSL synthesis in mature neurons remain elusive, since Nestin-Cre is expressed in neural precursors as well as in postmitotic neurons. To address this problem, we generated Purkinje cell-specific Ugcg knockout mice using mice that express Cre under the control of the L7 promoter. In these mice, Purkinje cells survived for at least 10-18 weeks after Ugcg deletion. We observed apparent axonal degeneration characterized by the accumulation of axonal transport cargos and aberrant membrane structures. Dendrites, however, were not affected. In addition, loss of GSLs disrupted myelin sheaths, which were characterized by detached paranodal loops. Notably, we observed doubly myelinated axons enveloped by an additional concentric myelin sheath around the original sheath. Our data show that axonal GlcCer-based GSLs are essential for axonal homeostasis and correct myelin sheath formation.


Assuntos
Axônios/metabolismo , Glucosiltransferases/metabolismo , Glicoesfingolipídeos/metabolismo , Bainha de Mielina/metabolismo , Células de Purkinje/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Transporte Axonal/fisiologia , Axônios/ultraestrutura , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Cerebelo/metabolismo , Cerebelo/ultraestrutura , Dendritos/metabolismo , Dendritos/ultraestrutura , Glucosiltransferases/genética , Glicoesfingolipídeos/biossíntese , Homeostase/fisiologia , Camundongos , Camundongos Knockout , Bainha de Mielina/ultraestrutura , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Neurônios/metabolismo , Neurônios/ultraestrutura , Células de Purkinje/ultraestrutura
19.
BMC Neurosci ; 11: 13, 2010 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-20137064

RESUMO

BACKGROUND: Microglia/macrophages and lymphocytes (T-cells) accumulate around motor and primary sensory neurons that are regenerating axons but there is little or no microglial activation or T-cell accumulation around axotomised intrinsic CNS neurons, which do not normally regenerate axons. We aimed to establish whether there was an inflammatory response around the perikarya of CNS neurons that were induced to regenerate axons through a peripheral nerve graft. RESULTS: When neurons of the thalamic reticular nucleus (TRN) and red nucleus were induced to regenerate axons along peripheral nerve grafts, a marked microglial response was found around their cell bodies, including the partial enwrapping of some regenerating neurons. T-cells were found amongst regenerating TRN neurons but not rubrospinal neurons. Axotomy alone or insertion of freeze-killed nerve grafts did not induce a similar perineuronal inflammation. Nerve grafts in the corticospinal tracts did not induce axonal regeneration or a microglial or T-cell response in the motor cortex. CONCLUSIONS: These results strengthen the evidence that perineuronal microglial accumulation (but not T-cell accumulation) is involved in axonal regeneration by intrinsic CNS and other neurons.


Assuntos
Axônios/fisiologia , Microglia/fisiologia , Regeneração Nervosa/fisiologia , Neurônios/fisiologia , Núcleo Rubro/fisiologia , Núcleos Talâmicos/fisiologia , Animais , Axotomia , Transplante de Tecido Encefálico , Morte Celular , Nervo Facial/fisiologia , Nervo Facial/cirurgia , Feminino , Congelamento , Masculino , Córtex Motor/fisiologia , Neurônios/transplante , Nervos Periféricos/cirurgia , Tratos Piramidais/fisiologia , Tratos Piramidais/cirurgia , Ratos , Ratos Sprague-Dawley , Núcleo Rubro/cirurgia , Linfócitos T/fisiologia , Núcleos Talâmicos/cirurgia
20.
J Vet Med Sci ; 72(3): 349-52, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19952512

RESUMO

We report a cervical intraspinal cyst in a dog that was initially tetraparetic but spontaneously recovered completely. MRI revealed a well-demarcated intraspinal cyst located dorsally to a degenerated intervertebral disc. The location of the cyst and its signal features on MRI resembled those of discal cysts previously reported in humans. It has been reported in dogs that clinical signs of a intraspinal cyst are similar to those of intervertebral disc herniation and both conditions require surgical intervention. Unexpectedly, our case showed rapid spontaneous recovery and the follow-up MRI revealed complete resolution of the intraspinal cyst and spinal cord compression. Spontaneous recovery of degenerative intraspinal cyst may occur in dogs, similar to rare human cases as reported previously.


Assuntos
Cistos/veterinária , Deslocamento do Disco Intervertebral/veterinária , Remissão Espontânea , Animais , Meios de Contraste , Cistos/patologia , Doenças do Cão/patologia , Cães , Feminino , Deslocamento do Disco Intervertebral/patologia , Imageamento por Ressonância Magnética/veterinária , Ovariectomia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...