Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Huntingtons Dis ; 4(1): 17-36, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26333255

RESUMO

BACKGROUND: Unusually large CAG repeat expansions (>60) in exon one of Huntingtin (HTT) are invariably associated with a juvenile-onset form of Huntington's disease (HD), characterized by a more extensive and rapidly progressing neuropathology than the more prevalent adult-onset form. However, existing mouse models of HD that express the full-length Htt gene with CAG repeat lengths associated with juvenile HD (ranging between ~75 to ~150 repeats in published models) exhibit selective neurodegenerative phenotypes more consistent with adult-onset HD. Objective: To determine if a very large CAG repeat (>200) in full-length Htt elicits neurodegenerative phenotypes consistent with juvenile HD. METHODS: Using a …bacterial artificial chromosome (BAC) system, we generated mice expressing full-length mouse Htt with ~225 CAG repeats under control of the mouse Htt promoter. Mice were characterized using behavioral, neuropathological, biochemical and brain imaging methods. RESULTS: BAC-225Q mice exhibit phenotypes consistent with a subset of features seen in juvenile-onset HD: very early motor behavior abnormalities, reduced body weight, widespread and progressive increase in Htt aggregates, gliosis, and neurodegeneration. Early striatal pathology was observed, including reactive gliosis and loss of dopamine receptors, prior to detectable volume loss. HD-related blood markers of impaired energy metabolism and systemic inflammation were also increased. Aside from an age-dependent progression of diffuse nuclear aggregates at 6 months of age to abundant neuropil aggregates at 12 months of age, other pathological and motor phenotypes showed little to no progression. CONCLUSIONS: The HD phenotypes present in animals 3 to 12 months of age make the BAC-225Q mice a unique and stable model of full-length mutant Htt associated phenotypes, including body weight loss, behavioral impairment and HD-like neurodegenerative phenotypes characteristic of juvenile-onset HD and/or late-stage adult-onset HD.


Assuntos
Comportamento Animal , Encéfalo/patologia , Doença de Huntington/genética , Camundongos , Neurônios/patologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Expansão das Repetições de Trinucleotídeos/genética , Animais , Atrofia , Encéfalo/metabolismo , Cromossomos Artificiais Bacterianos , Modelos Animais de Doenças , Progressão da Doença , Doença de Huntington/patologia , Doença de Huntington/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Fenótipo , Regiões Promotoras Genéticas
2.
Cereb Cortex ; 25(9): 2696-706, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24711485

RESUMO

This paper presents a comprehensive effort to establish a structural mouse connectome using diffusion tensor magnetic resonance imaging coupled with connectivity analysis tools. This work lays the foundation for imaging-based structural connectomics of the mouse brain, potentially facilitating a whole-brain network analysis to quantify brain changes in connectivity during development, as well as deviations from it related to genetic effects. A connectomic trajectory of maturation during postnatal ages 2-80 days is presented in the C57BL/6J mouse strain, using a whole-brain connectivity analysis, followed by investigations based on local and global network features. The global network measures of density, global efficiency, and modularity demonstrated a nonlinear relationship with age. The regional network metrics, namely degree and local efficiency, displayed a differential change in the major subcortical structures such as the thalamus and hippocampus, and cortical regions such as visual and motor cortex. Finally, the connectomes were used to derive an index of "brain connectivity index," which demonstrated a high correlation (r = 0.95) with the chronological age, indicating that brain connectivity is a good marker of normal age progression, hence valuable in detecting subtle deviations from normality caused by genetic, environmental, or pharmacological manipulations.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Conectoma , Imagem de Tensor de Difusão , Vias Neurais/crescimento & desenvolvimento , Fatores Etários , Animais , Animais Recém-Nascidos , Processamento de Imagem Assistida por Computador , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/anatomia & histologia
3.
Schizophr Bull ; 40(3): 575-84, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23716713

RESUMO

The glutamatergic hypothesis of schizophrenia suggests that hypoactivity of the N-methyl-D-aspartate receptor (NMDAR) is an important factor in the pathophysiology of schizophrenia and related mental disorders. The environmental neurotoxicant, lead (Pb(2+)), is a potent and selective antagonist of the NMDAR. Recent human studies have suggested an association between prenatal Pb(2+) exposure and the increased likelihood of schizophrenia later in life, possibly via interacting with genetic risk factors. In order to test this hypothesis, we examined the neurobehavioral consequences of interaction between Pb(2+) exposure and mutant disrupted in schizophrenia 1 (mDISC1), a risk factor for major psychiatric disorders. Mutant DISC1 and control mice born by the same dams were raised and maintained on a regular diet or a diet containing moderate levels of Pb(2+). Chronic, lifelong exposure of mDISC1 mice to Pb(2+) was not associated with gross developmental abnormalities but produced sex-dependent hyperactivity, exaggerated responses to the NMDAR antagonist, MK-801, mildly impaired prepulse inhibition of the acoustic startle, and enlarged lateral ventricles. Together, these findings support the hypothesis that environmental toxins could contribute to the pathogenesis of mental disease in susceptible individuals.


Assuntos
Comportamento Animal/efeitos dos fármacos , Interação Gene-Ambiente , Intoxicação por Chumbo/complicações , Chumbo/farmacologia , Proteínas do Tecido Nervoso/genética , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Esquizofrenia/genética , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Mutantes , Inibição Pré-Pulso/efeitos dos fármacos , Reflexo Anormal/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Esquizofrenia/etiologia , Esquizofrenia/fisiopatologia , Fatores Sexuais
4.
Int J Dev Neurosci ; 30(7): 554-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22940293

RESUMO

Abnormal neuroimmune responses have been reported to be associated with autism and could be appropriate targets for pharmacologic intervention. Our previous studies showed that neuroimmune factor, interleukin (IL)-6, was significantly elevated in the fontal cortex and cerebellum of autistic subjects. The IL-6 overexpressing mice displayed several autism-like features as well as an abnormal dendritic spine morphology and synaptic function. The purpose of this study was to examine the volumetric differences in the brain of IL-6 overexpressing mice and compare with corresponding control mice using magnetic resonance imaging. Here we show that IL-6 overexpressing mice display an increase in the total brain volume. In addition, the lateral ventricle is also enlarged in the IL-6 overexpressing mice. The brain structures surrounding the lateral ventricle were squeezed and deformed from the normal location. These results indicate that IL-6 elevation in the brain could mediate neuroanatomical abnormalities. Taking together with our previous findings, a mechanism by which IL-6 may be involved in the pathogenesis of autism is proposed.


Assuntos
Transtorno Autístico/genética , Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Interleucina-6/genética , Animais , Comportamento Animal/fisiologia , Dependovirus/genética , Vetores Genéticos , Processamento de Imagem Assistida por Computador , Interleucina-6/biossíntese , Ventrículos Laterais/crescimento & desenvolvimento , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Fixação de Tecidos
5.
Neuropharmacology ; 62(3): 1290-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21277874

RESUMO

Researchers have long noted an excess of patients with schizophrenia were born during the months of January and March. This winter birth effect has been hypothesized to result either from various causes such as vitamin D deficiency (McGrath, 1999; McGrath et al., 2010), or from maternal infection during pregnancy. Infection with a number of viruses during pregnancy including influenza, and rubella are known to increase the risk of schizophrenia in the offspring (Brown, 2006). Animal models using influenza virus or Poly I:C, a viral mimic, have been able to replicate many of the brain morphological, genetic, and behavioral deficits of schizophrenia (Meyer et al., 2006, 2008a, 2009; Bitanihirwe et al., 2010; Meyer and Feldon, 2010; Short et al., 2010). Using a murine model of prenatal viral infection, our laboratory has shown that viral infection on embryonic days 9, 16, and 18 leads to abnormal expression of brain genes and brain structural abnormalities in the exposed offspring (Fatemi et al., 2005, 2008a,b, 2009a,b). The purpose of the current study was to examine gene expression and morphological changes in the placenta, hippocampus, and prefrontal cortex as a result of viral infection on embryonic day 7 of pregnancy. Pregnant mice were either infected with influenza virus [A/WSN/33 strain (H1N1)] or sham-infected with vehicle solution. At E16, placentas were harvested and prepared for either microarray analysis or for light microscopy. We observed significant, upregulation of 77 genes and significant downregulation of 93 genes in placentas. In brains of exposed offspring following E7 infection, there were changes in gene expression in prefrontal cortex (6 upregulated and 24 downregulated at P0; 5 upregulated and 14 downregulated at P56) and hippocampus (4 upregulated and 6 downregulated at P0; 6 upregulated and 13 downregulated at P56). QRT-PCR verified the direction and magnitude of change for a number of genes associated with hypoxia, inflammation, schizophrenia, and autism. Placentas from infected mice showed a number of morphological abnormalities including presence of thrombi and increased presence of immune cells. Additionally, we searched for presence of H1N1 viral-specific genes for M1/M2, NA, and NS1 in placentas of infected mice and brains of exposed offspring and found none. Our results demonstrate that prenatal viral infection disrupts structure and gene expression of the placenta, hippocampus, and prefrontal cortex potentially explaining deleterious effects in the exposed offspring without evidence for presence of viral RNAs in the target tissues.


Assuntos
Encéfalo/virologia , Regulação da Expressão Gênica no Desenvolvimento , Regulação Viral da Expressão Gênica , Vírus da Influenza A Subtipo H1N1/genética , Placenta/virologia , Esquizofrenia/genética , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/patologia , Placenta/metabolismo , Placenta/patologia , Gravidez , Esquizofrenia/metabolismo , Esquizofrenia/patologia , Esquizofrenia/virologia
6.
Cereb Cortex ; 19(8): 1889-95, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19068488

RESUMO

In the human brain, different regions of the cortex communicate via white matter tracts. Investigation of this connectivity is essential for understanding brain function. It has been shown that trajectories of white matter fiber bundles can be estimated based on orientational information that is obtained from diffusion tensor imaging (DTI). By extrapolating this information, cortical regions associated with a specific white matter tract can be estimated. In this study, we created population-averaged cortical maps of brain connectivity for 4 major association fiber tracts, the corticospinal tract (CST), and commissural fibers. It is shown that these 4 association fibers interconnect all 4 lobes of the hemispheres. Cortical regions that were assigned based on association with the CST and the superior longitudinal fasciculus (SLF) agreed with locations of their known (CST: motor) or putative (SLF: language) functions. The proposed approach can potentially be used for quantitative assessment of the effect of white matter abnormalities on associated cortical regions.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiologia , Fibras Nervosas Mielinizadas/fisiologia , Vias Neurais/fisiologia , Adulto , Corpo Caloso/fisiologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Tratos Piramidais/fisiologia
7.
Neuroimage ; 43(3): 447-57, 2008 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-18692144

RESUMO

Structural delineation and assignment are the fundamental steps in understanding the anatomy of the human brain. The white matter has been structurally defined in the past only at its core regions (deep white matter). However, the most peripheral white matter areas, which are interleaved between the cortex and the deep white matter, have lacked clear anatomical definitions and parcellations. We used axonal fiber alignment information from diffusion tensor imaging (DTI) to delineate the peripheral white matter, and investigated its relationship with the cortex and the deep white matter. Using DTI data from 81 healthy subjects, we identified nine common, blade-like anatomical regions, which were further parcellated into 21 subregions based on the cortical anatomy. Four short association fiber tracts connecting adjacent gyri (U-fibers) were also identified reproducibly among the healthy population. We anticipate that this atlas will be useful resource for atlas-based white matter anatomical studies.


Assuntos
Anatomia Artística , Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Ilustração Médica , Adolescente , Adulto , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade
8.
Neuroimage ; 40(2): 570-582, 2008 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-18255316

RESUMO

Brain registration to a stereotaxic atlas is an effective way to report anatomic locations of interest and to perform anatomic quantification. However, existing stereotaxic atlases lack comprehensive coordinate information about white matter structures. In this paper, white matter-specific atlases in stereotaxic coordinates are introduced. As a reference template, the widely used ICBM-152 was used. The atlas contains fiber orientation maps and hand-segmented white matter parcellation maps based on diffusion tensor imaging (DTI). Registration accuracy by linear and non-linear transformation was measured, and automated template-based white matter parcellation was tested. The results showed a high correlation between the manual ROI-based and the automated approaches for normal adult populations. The atlases are freely available and believed to be a useful resource as a target template and for automated parcellation methods.


Assuntos
Mapeamento Encefálico , Encéfalo/anatomia & histologia , Adolescente , Adulto , Atlas como Assunto , Humanos , Pessoa de Meia-Idade
9.
Neuroimage ; 39(1): 336-47, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17931890

RESUMO

Diffusion tensor imaging (DTI) is an exciting new MRI modality that can reveal detailed anatomy of the white matter. DTI also allows us to approximate the 3D trajectories of major white matter bundles. By combining the identified tract coordinates with various types of MR parameter maps, such as T2 and diffusion properties, we can perform tract-specific analysis of these parameters. Unfortunately, 3D tract reconstruction is marred by noise, partial volume effects, and complicated axonal structures. Furthermore, changes in diffusion anisotropy under pathological conditions could alter the results of 3D tract reconstruction. In this study, we created a white matter parcellation atlas based on probabilistic maps of 11 major white matter tracts derived from the DTI data from 28 normal subjects. Using these probabilistic maps, automated tract-specific quantification of fractional anisotropy and mean diffusivity were performed. Excellent correlation was found between the automated and the individual tractography-based results. This tool allows efficient initial screening of the status of multiple white matter tracts.


Assuntos
Encéfalo/citologia , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Fibras Nervosas Mielinizadas/ultraestrutura , Vias Neurais/anatomia & histologia , Reconhecimento Automatizado de Padrão/métodos , Adulto , Algoritmos , Inteligência Artificial , Simulação por Computador , Interpretação Estatística de Dados , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Modelos Neurológicos , Modelos Estatísticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Neuroimage ; 36(3): 630-44, 2007 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-17481925

RESUMO

Tractography based on diffusion tensor imaging (DTI) allows visualization of white matter tracts. In this study, protocols to reconstruct eleven major white matter tracts are described. The protocols were refined by several iterations of intra- and inter-rater measurements and identification of sources of variability. Reproducibility of the established protocols was then tested by raters who did not have previous experience in tractography. The protocols were applied to a DTI database of adult normal subjects to study size, fractional anisotropy (FA), and T2 of individual white matter tracts. Distinctive features in FA and T2 were found for the corticospinal tract and callosal fibers. Hemispheric asymmetry was observed for the size of white matter tracts projecting to the temporal lobe. This protocol provides guidelines for reproducible DTI-based tract-specific quantification.


Assuntos
Encéfalo/anatomia & histologia , Vias Neurais/anatomia & histologia , Adulto , Anisotropia , Contagem de Células , Bases de Dados Factuais , Imagem de Difusão por Ressonância Magnética , Feminino , Giro do Cíngulo/citologia , Giro do Cíngulo/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Fibras Nervosas/fisiologia , Variações Dependentes do Observador , Tratos Piramidais/anatomia & histologia , Tratos Piramidais/fisiologia , Valores de Referência , Reprodutibilidade dos Testes , Tálamo/anatomia & histologia , Tálamo/fisiologia
11.
Neuroimage ; 29(2): 493-504, 2006 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-16194615

RESUMO

Recent advances in diffusion tensor imaging (DTI) have made it possible to reveal white matter anatomy and to detect neurological abnormalities in children. However, the clinical use of this technique is hampered by the lack of a normal standard of reference. The goal of this study was to initiate the establishment of a database of DTI images in children, which can be used as a normal standard of reference for diagnosis of pediatric neurological abnormalities. Seven pediatric volunteers and 23 pediatric patients (age range: 0-54 months) referred for clinical MR examinations, but whose brains were shown to be normal, underwent anatomical and DTI acquisitions on a 1.5 T MR scanner. The white matter maturation, as observed on DTI color maps, was described and illustrated. Changes in diffusion fractional anisotropy (FA), average apparent diffusion constant (ADC(ave)), and T2-weighted (T2W) signal intensity were quantified in 12 locations to characterize the anatomical variability of the maturation process. Almost all prominent white matter tracts could be identified from birth, although their anisotropy was often low. The evolution of FA, shape, and size of the white matter tracts comprised generally three phases: rapid changes during the first 12 months; slow modifications during the second year; and relative stability after 24 months. The time courses of FA, ADC(ave), and T2W signal intensity confirmed our visual observations that maturation of the white matter and the normality of its architecture can be assessed with DTI in young children. The database is available online and is expected to foster the use of this promising technique in the diagnosis of pediatric pathologies.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/citologia , Mapeamento Encefálico , Tronco Encefálico/anatomia & histologia , Tronco Encefálico/citologia , Tronco Encefálico/crescimento & desenvolvimento , Pré-Escolar , Bases de Dados Factuais , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Recém-Nascido , Sistema Límbico/anatomia & histologia , Sistema Límbico/citologia , Sistema Límbico/crescimento & desenvolvimento , Masculino , Fibras Nervosas/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/crescimento & desenvolvimento , Valores de Referência , Software
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 11(1): 92-5, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12667299

RESUMO

In order to acquire freezing model of the cryopretective solution (NaCl-propylene glycol-water ternary system) for platelet, the melting points (T(f)) of this cryopretective solutions with different solute concentration and different ratio of PG mass to NaCl mass were measured by using a differential scanning calorimeter (DSC), and these experimental data were fitting by computer. An empirical equation was derived which characterized the Tf as a function of the solute concentration and the ratio of PG mass to NaCl mass inside this solution. It was concluded that the equilibrium freezing model for human platelets in this system could be used to instruct platelet cryopreserving techniques.


Assuntos
Plaquetas , Criopreservação/métodos , Crioprotetores/química , Soluções para Preservação de Órgãos/química , Plaquetas/efeitos dos fármacos , Crioprotetores/farmacologia , Humanos , Modelos Químicos , Soluções para Preservação de Órgãos/farmacologia , Propilenoglicol/química , Propilenoglicol/farmacologia , Cloreto de Sódio/química , Cloreto de Sódio/farmacologia , Temperatura , Água/química , Água/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...