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1.
Dev Biol ; 462(1): 101-115, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243888

RESUMO

Drosophila Larval hematopoiesis takes place at the lymph gland, where myeloid-like progenitors differentiate into Plasmatocytes and Crystal Cells, under regulation of conserved signaling pathways. It has been established that the Notch pathway plays a specific role in Crystal Cell differentiation and maintenance. In mammalian hematopoiesis, the Notch pathway has been proposed to fulfill broader functions, including Hematopoietic Stem Cell maintenance and cell fate decision in progenitors. In this work we describe different roles that Notch plays in the lymph gland. We show that Notch, activated by its ligand Serrate, expressed at the Posterior Signaling Center, is required to restrain Core Progenitor differentiation. We define a novel population of blood cell progenitors that we name Distal Progenitors, where Notch, activated by Serrate expressed in Lineage Specifying Cells at the Medullary Zone/Cortical Zone boundary, regulates a binary decision between Plasmatocyte and Crystal Cell fates. Thus, Notch plays context-specific functions in different blood cell progenitor populations of the Drosophila lymph gland.


Assuntos
Células-Tronco Hematopoéticas/citologia , Linfonodos/metabolismo , Receptores Notch/metabolismo , Animais , Células Sanguíneas/citologia , Diferenciação Celular/fisiologia , Linhagem da Célula , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/metabolismo , Hematopoese/fisiologia , Proteína Jagged-1/metabolismo , Larva/metabolismo , Receptores Notch/fisiologia , Transdução de Sinais/fisiologia
2.
Chem Commun (Camb) ; 52(28): 4971-4, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-26862591

RESUMO

The stability of UiO-67 has been questioned for some time. We have used solid-state NMR to investigate the temporal stability of this MOF. Proper activation is necessary to achieve optimal surface area. However, even with proper activation, the long-term (30+ days) fate of UiO-67 is hydrolysis of the linker-metal bonds and, ultimately, pore collapse.

3.
Cell Mol Life Sci ; 73(9): 1881-93, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26874685

RESUMO

Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post-transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read-through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress.


Assuntos
Estresse Oxidativo , Bactérias/metabolismo , Códon de Terminação , Dioxigenases/metabolismo , Humanos , Hidroxilação , Processamento de Proteína Pós-Traducional , RNA de Transferência/genética , RNA de Transferência/metabolismo , Proteínas Ribossômicas/metabolismo
4.
Obs Stud ; 1(2015): 56-73, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25984574

RESUMO

Longitudinal cognitive trajectories and other factors associated with mixed neuropathologies (such as Alzheimer's disease with co-occurring cerebrovascular disease) remain incompletely understood, despite being the rule and not the exception in older populations. The Statistical Modeling of Aging and Risk of Transition study (SMART) is a consortium of 11 different high-quality longitudinal studies of aging and cognition (N=11,541 participants) established for the purpose of characterizing risk and protective factors associated with subtypes of age-associated mixed neuropathologies (N=3,001 autopsies). While brain donation was not required for participation in all SMART cohorts, most achieved substantial autopsy rates (i.e., > 50%). Moreover, the studies comprising SMART have large numbers of participants who were followed from intact cognition and transitioned to cognitive impairment and dementia, as well as participants who remained cognitively intact until death. These data provide an exciting opportunity to apply sophisticated statistical methods, like Markov processes, that require large, well-characterized samples. Thus, SMART will serve as an important resource for the field of mixed dementia epidemiology and neuropathology.

5.
Neurology ; 73(5): 356-61, 2009 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-19652139

RESUMO

BACKGROUND: Persons destined to develop dementia experience an accelerated rate of decline in cognitive ability, particularly in memory. Early life education and participation in cognitively stimulating leisure activities later in life are 2 factors thought to reflect cognitive reserve, which may delay the onset of the memory decline in the preclinical stages of dementia. METHODS: We followed 488 initially cognitively intact community residing individuals with epidemiologic, clinical, and cognitive assessments every 12 to 18 months in the Bronx Aging Study. We assessed the influence of self-reported participation in cognitively stimulating leisure activities on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. RESULTS: Each additional self-reported day of cognitive activity at baseline delayed the onset of accelerated memory decline by 0.18 years. Higher baseline levels of cognitive activity were associated with more rapid memory decline after that onset. Inclusion of education did not significantly add to the fit of the model beyond the effect of cognitive activities. CONCLUSIONS: Our findings show that late life cognitive activities influence cognitive reserve independently of education. The effect of early life education on cognitive reserve may be mediated by cognitive activity later in life. Alternatively, early life education may be a determinant of cognitive reserve, and individuals with more education may choose to participate in cognitive activities without influencing reserve. Future studies should examine the efficacy of increasing participation in cognitive activities to prevent or delay dementia.


Assuntos
Cognição/fisiologia , Demência/complicações , Demência/prevenção & controle , Atividades de Lazer/psicologia , Transtornos da Memória/etiologia , Transtornos da Memória/prevenção & controle , Atividades Cotidianas/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Demência/reabilitação , Escolaridade , Exercício Físico/fisiologia , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Transtornos da Memória/reabilitação , Modelos Estatísticos , Autoavaliação (Psicologia)
6.
Neurology ; 70(18): 1594-600, 2008 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-18367703

RESUMO

BACKGROUND: Characterization of the behavioral correlates of neuromorphometry and neurochemistry in older adults has important implications for an improved understanding of the aging process. The objective of this study was to test the hypothesis that a measure of hippocampal neuronal metabolism was associated with verbal memory in nondemented older adults after controlling for hippocampal volume. METHODS: 4-T MRI, proton magnetic resonance spectroscopy ((1)H MRS), and neuropsychological assessment were conducted in 48 older adults (23 women; mean age 81 years). Average hippocampal N-acetyl aspartate/creatine ratios (NAA/Cr) and hippocampal volumes were obtained. Neuropsychological evaluation included tests of verbal memory (Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall [FCSRT-IR], Wechsler Memory Scale-Revised Logical Memory subtest) and attention and executive function (Trail Making Test Parts A and B). RESULTS: Linear regression analysis indicated that after adjusting for age, hippocampal NAA/Cr was a significant predictor of FCSRT-IR performance (beta = 0.38, p = 0.01, R (2) = 0.21). Hippocampal volume was also a significant predictor of FCSRT-IR performance after adjusting for age and midsagittal area (beta = 0.47, p = 0.01, R (2) = 0.24). In a combined model, hippocampal NAA/Cr (beta = 0.33, p = 0.03) and volume (beta = 0.35, p = 0.03) were independent predictors of FCSRT-IR performance, accounting for 30% of the variance in memory. CONCLUSIONS: These findings indicate that nondemented older adults with smaller hippocampal volumes and lower levels of hippocampal N-acetyl aspartate/creatine ratio metabolites perform more poorly on a test of verbal memory. The integrity of both the structure and metabolism of the hippocampus may underlie verbal memory function in nondemented elderly.


Assuntos
Envelhecimento/patologia , Envelhecimento/psicologia , Hipocampo/fisiologia , Memória , Comportamento Verbal , Idoso , Idoso de 80 Anos ou mais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Creatina/análise , Feminino , Hipocampo/anatomia & histologia , Hipocampo/química , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/patologia , Testes Neuropsicológicos , Tamanho do Órgão , Estudos de Amostragem
7.
Neurology ; 69(17): 1657-64, 2007 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-17954781

RESUMO

OBJECTIVE: To test the cognitive reserve hypothesis by examining the effect of education on memory decline during the preclinical course of dementia. BACKGROUND: Low education is a well known risk factor for Alzheimer disease (AD). Persons destined to develop AD experience an accelerated rate of decline in cognitive ability, particularly in memory. The cognitive reserve hypothesis predicts that persons with greater education begin to experience acceleration in cognitive decline closer to the time of diagnosis than persons with lower reserve, but that their rate of decline is more rapid after the time of acceleration due to increased disease burden. METHODS: We studied the influence of education on rates of memory decline as measured by the Buschke Selective Reminding Test in 117 participants with incident dementia in the Bronx Aging Study. Subjects had detailed cognitive assessments at entry and at annual follow-up visits. We estimated the time at which the rate of decline begins to accelerate (the change point), and the pre- and post-acceleration rates of decline, from the longitudinal data using a change point model. RESULTS: Each additional year of formal education delayed the time of accelerated decline on the Buschke Selective Reminding Test by 0.21 years. Post-acceleration, the rate of memory decline was increased by 0.10 points per year for each year of additional formal education. CONCLUSIONS: As predicted by the cognitive reserve hypothesis, higher education delays the onset of accelerated cognitive decline; once it begins it is more rapid in persons with more education.


Assuntos
Demência/diagnóstico , Escolaridade , Memória/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Demência/psicologia , Progressão da Doença , Feminino , Humanos , Masculino , Testes Neuropsicológicos
8.
J Neural Transm (Vienna) ; 114(10): 1249-52, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17541695

RESUMO

We defined a 'high-risk neurological gait' (HRNG) syndrome based on presence of any one of hemiparetic, frontal, and unsteady gaits, and examined its validity to predict vascular dementia (VD) over 3 and 5 years in 399 nondemented older adults, age 75 and over. Cox analysis was used to estimate hazard ratios (HR) for VD adjusted for potential confounders. At baseline, 54 subjects had HRNG. 14 subjects developed VD over 3 years and 25 by 5 years. HRNG predicted risk of VD within the first three (HR 3.3, 95% CI 1.8-5.9) and five years (HR 2.7, 95% CI 1.7-4.2). Including executive dysfunction (Digit symbol scores <16) improved validity; subjects with HRNG and executive dysfunction (HR 12.5, 95% CI 5.5-28.4) or either (HR 5.9, 95% CI 3.6-9.7) had higher risk of VD over five years. Diagnosing HRNG is a clinically relevant approach to identifying older adults at high risk of VD over short intervals.


Assuntos
Demência Vascular/epidemiologia , Transtornos Neurológicos da Marcha/epidemiologia , Risco , Idoso , Idoso de 80 Anos ou mais , Demência Vascular/etiologia , Feminino , Seguimentos , Transtornos Neurológicos da Marcha/complicações , Humanos , Masculino , Testes Neuropsicológicos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Neurology ; 61(12): 1667-72, 2003 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-14694027

RESUMO

BACKGROUND: The role of blood pressure (BP) as a risk factor for dementia is complex and may be age dependent. In very old individuals, low BP might increase risk for dementia, perhaps by reducing cerebral perfusion pressure. METHODS: The association between BP and dementia was examined in the Bronx Aging Study, a prospective study of 488 community-dwelling elderly individuals over age 75, dementia-free at baseline (1980 to 1983) and followed at 12- to 18-month intervals. Subjects with baseline BP and with at least one follow-up visit were included (n = 406). Incident dementia was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd rev. ed.). RESULTS: Over 21 years (median 6.7 years), 122 subjects developed dementia (65 Alzheimer's disease [AD], 28 vascular dementia, 29 other dementias). Relative risk of dementia increased for each 10-mm Hg decrement in diastolic (hazard ratio [HR] 1.20, 95% CI 1.03 to 1.40) and mean arterial (HR 1.16, 95% CI 1.02 to 1.32) pressure, adjusted for age, sex, and education. Low diastolic BP significantly influenced risk of developing AD but not vascular dementia. Upon examination of groups defined by BP, mildly to moderately raised systolic BP (140 to 179 mm Hg) was associated with reduced risk for AD (HR vs normal systolic BP group 0.55, 95% CI 0.32 to 0.96), whereas low diastolic BP (

Assuntos
Demência/epidemiologia , Hipotensão/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Comorbidade , Fatores de Confusão Epidemiológicos , Demência/diagnóstico , Demência Vascular/epidemiologia , Demografia , Diástole , Feminino , Humanos , Hipotensão/classificação , Masculino , Cidade de Nova Iorque/epidemiologia , Modelos de Riscos Proporcionais , Medição de Risco , Sístole
10.
Neurology ; 55(6): 872-4, 2000 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-10994013

RESUMO

Estrogen replacement therapy (ERT) may help maintain normal cognitive function. Nondemented surgically menopausal women on ERT (n = 10) enrolled in a longitudinal aging study performed better than age- and education-matched control subjects (n = 25) on selected tests of verbal memory and constructional ability. These results suggest that ERT initiated soon after surgical menopause can have long-term neuroprotective effects in cognitively intact women.


Assuntos
Cognição/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Histerectomia , Menopausa Precoce/efeitos dos fármacos , Menopausa Precoce/psicologia , Idoso , Feminino , Humanos , Testes Neuropsicológicos
11.
J Comp Neurol ; 422(3): 415-28, 2000 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-10861517

RESUMO

Dendritic trees often are complex, three-dimensional structures. Comparative morphologic studies have not yet provided a reliable measure to analyze and compare the geometry of different dendritic trees. Therefore, it is important to develop quantitative methods for analyzing the three-dimensional geometry of these complex trees. The authors developed a comparison measure based on the Hausdorff distance for comparing quantitatively the three-dimensional structure of different neurons. This algorithm was implemented and incorporated into a new software package that the authors developed called NeuroComp. The authors tested this algorithm to study the variability in the three-dimensional structure of identified central neurons as well as measuring the structural differences between homologue neurons. They took advantage of the uniform dendritic morphology of identified interneurons of an insect, the giant interneurons of the cockroach. More specifically, after establishing a morphometric data base of these neurons, the authors found that the algorithm is a reliable tool for distinguishing between dendritic trees of different neurons, whereas conventional metric analysis often is inadequate. The authors propose to use this method as a quantitative tool for the investigation of the effects of various experimental paradigms on three-dimensional dendritic architecture.


Assuntos
Baratas/anatomia & histologia , Dendritos/ultraestrutura , Interneurônios/ultraestrutura , Neurologia/métodos , Algoritmos , Animais , Processamento de Imagem Assistida por Computador , Software
12.
Brain Res ; 616(1-2): 58-64, 1993 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-7689412

RESUMO

Neurofilaments (NFs) were radiolabeled in the optic systems of mice. The leading edge of the radiolabeled NF waveform was distinguished near the injection site (the eye) both by liquid scintillation spectroscopy and visually from fluorographs. The fastest NFs were found to be translocated at rates of between 72 and 144 mm/day. It appears that the continuous (maximal) operation of the slow axonal transport machinery can move polymers intra-axonally at rates one hundred times greater than those previously reported.


Assuntos
Axônios/fisiologia , Filamentos Intermediários/metabolismo , Proteínas de Neurofilamentos/metabolismo , Nervo Óptico/fisiologia , Animais , Transporte Axonal , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Cinética , Masculino , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Neurofilamentos/isolamento & purificação , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/fisiologia , Radioisótopos de Enxofre , Fatores de Tempo
13.
Brain Res ; 607(1-2): 125-33, 1993 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-8481791

RESUMO

Neurofilament distributions were mathematically characterized in four chicken somatic motor axons at each of four histologically distinct regions: compact myelinated regions, compact myelinated regions associated with Schwann cell nuclei, Schmidt-Lanterman clefts, and nodes of Ranvier. Compact myelinated regions had the largest cross-sectional areas, the lowest neurofilament densities, and the most random neurofilament organizations--nodes of Ranvier had the smallest cross-sectional areas, the highest neurofilament densities, and the most ordered architectures. In these myelinated axons, the closest natural neurofilament spacing was 25 nm. Mathematical analyses of serial sections suggested that neurofilament interactions are sufficiently weak and transient to permit a full range of variation from random to ordered cytoskeletal architectures as the neurofilaments move longitudinally through the few micron span of the paranodal-nodal region of a single axon.


Assuntos
Axônios/ultraestrutura , Filamentos Intermediários/ultraestrutura , Animais , Núcleo Celular/ultraestrutura , Galinhas , Histocitoquímica , Masculino , Neurônios Motores/ultraestrutura , Bainha de Mielina/ultraestrutura , Nós Neurofibrosos/ultraestrutura , Células de Schwann/ultraestrutura
14.
J Cell Biol ; 117(3): 607-16, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1374068

RESUMO

Pulse-labeling studies of slow axonal transport in many kinds of axons (spinal motor, sensory ganglion, oculomotor, hypoglossal, and olfactory) have led to the inference that axonal transport mechanisms move neurofilaments (NFs) unidirectionally as a single continuous kinetic population with a diversity of individual transport rates. One study in mouse optic axons (Nixon, R. A., and K. B. Logvinenko. 1986. J. Cell Biol. 102:647-659) has given rise to the different suggestion that a significant and distinct population of NFs may be entirely stationary within axons. In mouse optic axons, there are relatively few NFs and the NF proteins are more lightly labeled than other slowly transported slow component b (SCb) proteins (which, however, move faster than the NFs); thus, in mouse optic axons, the radiolabel of some of these faster-moving SCb proteins may confuse NF protein analyses that use one dimensional (1-D) SDS-PAGE, which separates proteins by size only. To test this possibility, we used a 2-mm "window" (at 3-5 mm from the posterior of the eye) to compare NF kinetics obtained by 1-D SDS-PAGE and by the higher resolution two-dimensional (2-D) isoelectric focusing/SDS-PAGE, which separates proteins both by their net charge and by their size. We found that 1-D SDS-PAGE is insufficient for definitive NF kinetics in the mouse optic system. By contrast, 2-D SDS-PAGE provides essentially pure NF kinetics, and these indicate that in the NF-poor mouse optic axons, most NFs advance as they do in other, NF-rich axons. In mice, greater than 97% of the radiolabeled NFs were distributed in a unimodal wave that moved at a continuum of rates, between 3.0 and 0.3 mm/d, and less than 0.1% of the NF population traveled at the very slowest rates of less than 0.005 mm/d. These results are inconsistent with the proposal (Nixon and Logvinenko, 1986) that 32% of the transported NFs remain within optic axons in an entirely stationary state. As has been found in other axons, the axonal transport system of mouse optic axons moves NFs and other cytoskeletal elements relentlessly from the cell body to the axon tip.


Assuntos
Transporte Axonal , Axônios/metabolismo , Filamentos Intermediários/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Nervo Óptico/metabolismo , Animais , Transporte Biológico , Citoplasma/metabolismo , Eletroforese em Gel Bidimensional , Focalização Isoelétrica , Marcação por Isótopo , Cinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Neurofilamentos/metabolismo
15.
Brain Res ; 540(1-2): 209-16, 1991 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-2054613

RESUMO

Ultrastructural morphometry was used to document the non-random spatial distributions of organelles within the compact myelinated region of avian oculomotor axons. These regions contain large numbers of loosely packed neurofilaments (NFs) (241/microns 2) and only a relatively small number of microtubules (MTs) (4/microns 2), mitochondria (0.6/microns 2), and smooth endoplasmic reticulum (SER) (1.6/microns 2). Random co-occurrences between the relatively sparsely distributed MTs, mitochondria, and SER are probably infrequent in these axons. The actual co-occurrences of MTs, mitochondria, and SER with MTs were counted and compared to the co-occurrences expected in a random Poisson distribution. At long distances (200 nm), the co-occurrences were random. At shorter distances (40 nm and less), MTs were still randomly associated with other MTs. However, at these shorter distances, the spatial associations of mitochondria with MTs and of SER with MTs were not random; such preferential stable associations may be produced by specific MT associated cross-bridging proteins. In axons, MTs tend to be clustered together, giving the appearance of MT bundles. We propose that the MT-MT bundling is an indirect result of MT concentration along the continuous intra-axonal SER network, to which the MTs are apparently tied directly by dynamic molecular cross-bridges.


Assuntos
Axônios/ultraestrutura , Retículo Endoplasmático/ultraestrutura , Microtúbulos/ultraestrutura , Mitocôndrias/ultraestrutura , Nervo Oculomotor/ultraestrutura , Animais , Galinhas , Masculino , Microscopia Eletrônica
16.
Brain Res ; 530(2): 205-14, 1990 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-1702341

RESUMO

The cross-sectional architecture of the axon and the area of its surrounding Schwann cell were quantified at selected histological regions along the length of avian myelinated axons. The number of neurofilaments (NFs), the density of NFs, axoplasmic area, and Schwann cell cross-sectional area were measured. These parameters were examined at Schmidt-Lanterman (S-L) clefts, at paranodal-nodal regions, and at regions of compact myelin Schwann cell nuclei. The results were then compared with the same parameters in adjacent compact myelinated regions of the same axons. At S-L clefts, paranodal-nodal regions, and Schwann cell nuclei, the axonal areas were smaller and the NF densities were higher than at compact myelinated regions. From other studies, it has been suggested that NF organization is responsive to local compressive forces--NF packing density tends to increase with increasing compression of the axon. We found that the NF packing densities were relatively small and the axon diameters were relatively large in the compact myelinated regions; this result suggests that in these axonal regions external constraints on axonal architecture are minimal. The higher NF packing densities and smaller axon diameters in the other histological regions suggest that external compressive effects on the axon increase in the following order: simple compact myelin less than Schwann cell nucleus less than S-L cleft less than paranodal-nodal region. Ultrastructural comparisons of these 4 histological regions show that the Schwann cell cross-sectional areas differ reproducibly, and this is consistent with the idea that variations in the organization of extra-axonal elements that envelop the axon produce different amounts of physical constraint on the axon and that this can affect the amount of external pressure on the internal architecture of the axon.


Assuntos
Axônios/ultraestrutura , Citoesqueleto/ultraestrutura , Animais , Transporte Axonal/fisiologia , Núcleo Celular/ultraestrutura , Galinhas , Citoplasma/ultraestrutura , Filamentos Intermediários/ultraestrutura , Masculino , Bainha de Mielina/ultraestrutura , Músculos Oculomotores/inervação , Pressão , Células de Schwann/ultraestrutura
17.
Brain Res ; 517(1-2): 143-50, 1990 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-1695860

RESUMO

The window method of radiolabeled protein analysis was used to study the transport kinetics of axonally transported cytomatrix proteins as they move through segments of mouse optic axons. Three slow component b (SCb) proteins--actin, a 30 kDa protein, and clathrin--were radiolabeled in the eye and were followed for up to 119 days by quantitative one-dimensional gel electrophoresis. These proteins appeared first in the optic nerve, next in the tract, and last in the superior colliculus. All of the radiolabeled proteins had passed through the optic axons and had been effectively removed from the terminals by 119 days. Two different axonal segments ('windows') were examined in detail: a segment of the axon shaft region in the optic tract, and a segment of axon terminal region in the midbrain superior colliculus. The median transit times of the 3 proteins were 53-100% longer in the colliculus than in the tract, and the pulse transients (the total area under the transport curve in each window) were 180-350% larger in the colliculus than in the tract. These results indicate that at least certain cytomatrix and cytoskeletal proteins have longer residence times in the terminal regions than in the axon proper.


Assuntos
Actinas/metabolismo , Transporte Axonal/fisiologia , Clatrina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Nervo Óptico/metabolismo , Colículos Superiores/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular
18.
Brain Res ; 504(2): 223-30, 1989 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-2480832

RESUMO

The transport kinetics of 3 radiolabeled slow component b (SCb) proteins (a 30 kDa protein, clathrin, and actin) were examined in the axons of mouse retinal ganglion cells. To view the transit of these proteins through the entire optic pathway between the eye and the target cells, we used two different windows: (1) a 2 mm segment from the optic nerve located 3-5 mm from the eye, and (2) a 2 mm segment from the optic tract located past the chiasm 6-8 mm from the eye. The radiolabeled proteins from these windows were separated by 1- and 2-dimensional SDS-PAGE, and the individual radiolabeled bands were quantified. Radiolabeled proteins entered and cleared the optic axons between 1 and 119 days post-labeling. All these proteins had broader transport waves in the more distal optic tract window than in the more proximal optic nerve window. The spreading of transport waves as they advance along the axon appears to be produced by a playing out of the natural heterogeneity of axonal transport rates within each population of labeled proteins. Our results confirm the proposals that clathrin and the 30 kDa protein are transported principally with SCb and that actin is transported both with SCb and with SCa. Although these proteins can be generally classified with SCb, their detailed kinetics differed (for example, their median transit times differed) and, in summary, their characteristic rates of movement can be ordered as: clathrin greater than 30 kDa protein greater than actin.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Transporte Axonal , Proteínas do Tecido Nervoso/metabolismo , Nervo Óptico/metabolismo , Retina/metabolismo , Células Ganglionares da Retina/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular
19.
J Neuropathol Exp Neurol ; 48(1): 23-32, 1989 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2908896

RESUMO

In 2,5-hexanedione (2,5-HD)-induced axonal neuropathy, the rate of neurofilament (NF) transport increases in optic axons. To test the prediction that increases in the rate of polymer transport in any one locality of the axon lead directly to a decrease in the number of NF in that locality, NF and microtubules (MT) were quantitatively analyzed in axonal cross sections. In 2,5-HD axons the number of NF was 38% of that in control axons while the number of MT was not significantly changed; it appears that the drug treatment decreases NF number in the proximal axon regions, most directly through an increase in rate of NF transport. In those regions, the cross-sectional areas of the 2,5-HD-treated axons were 45% smaller than those of control axons; although the axons had shrunk in diameter, they retained their normal cylindrical shapes as measured by the index of circularity. Reduced internal expansive forces in the axon, working in conjunction with the normal external compressive forces, appear to reduce the radius of the axon. Quantitative analyses demonstrated that the average and the maximum lateral spacings between NF-NF, NF-MT, and MT-MT were all 30% larger in 2,5-HD-treated axons than in control axons. This suggests that polymers are relatively free to move laterally away from one another and to fill the available space within the axon. These observations are not consistent with models wherein 2,5-HD acts to crosslink the NF into an immobile network that can no longer advance within the axon. Instead, it appears more likely that 2,5-HD acts selectively on the interaction between some NF and the slow transport mechanism to increase the rate of NF transport.


Assuntos
Axônios/ultraestrutura , Citoesqueleto/metabolismo , Filamentos Intermediários/metabolismo , Animais , Transporte Biológico , Hexanonas/farmacologia , Filamentos Intermediários/ultraestrutura , Masculino , Microscopia Eletrônica , Microtúbulos/ultraestrutura , Nervo Óptico/ultraestrutura , Ratos , Ratos Endogâmicos
20.
J Neurocytol ; 17(1): 55-62, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3418356

RESUMO

The organization of the cytoskeleton is compared in the large myelinated parasympathetic and somatic motor axons of the avian oculomotor system. Electron microscopic studies demonstrate that neurofilaments are the chief structural elements in these axons, and quantitative analyses of the distribution of neurofilaments in axonal cross-sections found that the average neurofilament packing density is 25% greater in the parasympathetic axons than in the somatic motor axons. In both types of axon the distributions of neurofilaments matched a randomly generated (Poisson) distribution. In axoplasm, a Poisson distribution could arise if the neurofilaments were distributed in the cross-sectional plane by stochastic forces operating randomly and without significant neurofilament-neurofilament interactions. Thus, in these axons, the neurofilaments behave as if they are inert 'molecules' in a dilute solution-subject to non-specific stochastic forces that tend to distribute them at random. We propose that neurofilaments normally are relatively free to move apart from each other and to fill the available space within the axon.


Assuntos
Axônios/ultraestrutura , Citoesqueleto/ultraestrutura , Filamentos Intermediários/ultraestrutura , Animais , Galinhas , Masculino , Microscopia Eletrônica , Microtúbulos/ultraestrutura , Mitocôndrias/ultraestrutura , Neurônios Motores/ultraestrutura , Bainha de Mielina/ultraestrutura , Nervo Oculomotor/ultraestrutura , Sistema Nervoso Parassimpático/ultraestrutura , Probabilidade
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