Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Elife ; 72018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30387711

RESUMO

Although failure of GABAergic inhibition is a commonly hypothesized mechanism underlying seizure disorders, the series of events that precipitate a rapid shift from healthy to ictal activity remain unclear. Furthermore, the diversity of inhibitory interneuron populations poses a challenge for understanding local circuit interactions during seizure initiation. Using a combined optogenetic and electrophysiological approach, we examined the activity of identified mouse hippocampal interneuron classes during chemoconvulsant seizure induction in vivo. Surprisingly, synaptic inhibition from parvalbumin- (PV) and somatostatin-expressing (SST) interneurons remained intact throughout the preictal period and early ictal phase. However, these two sources of inhibition exhibited cell-type-specific differences in their preictal firing patterns and sensitivity to input. Our findings suggest that the onset of ictal activity is not associated with loss of firing by these interneurons or a failure of synaptic inhibition but is instead linked with disruptions of the respective roles these interneurons play in the hippocampal circuit.


Assuntos
Hipocampo/patologia , Interneurônios/fisiologia , Convulsões/fisiopatologia , Potenciais de Ação , Animais , Eletroencefalografia , Camundongos , Optogenética , Convulsões/induzido quimicamente
2.
Nat Neurosci ; 17(8): 1123-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24997763

RESUMO

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.


Assuntos
Química Encefálica/fisiologia , Halobacterium salinarum/fisiologia , Halorrodopsinas/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Optogenética/métodos , Animais , Camundongos , Dados de Sequência Molecular , Retina/fisiologia
3.
J Acquir Immune Defic Syndr ; 58(5): 463-8, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21963941

RESUMO

BACKGROUND: Upon initiation of antiretroviral therapy (ART), 15.7% [95% confidence interval (CI): 9.7% to 24.5%] of tuberculosis (TB)-HIV-coinfected individuals experience paradoxical worsening of their clinical status with exuberant inflammation consistent with immune reconstitution inflammatory syndrome (IRIS). We investigated whether a positive urinary TB lipoarabinomannan (LAM) antigen enzyme-linked immunosorbent assay test before ART initiation was associated with development of paradoxical TB-IRIS. METHODS: In a prospective observational cohort in Mulago Hospital, Kampala, Uganda, we measured pre-ART urinary LAM concentrations in HIV-infected patients on TB treatment. Patients who developed TB-IRIS (according to the International Network for the Study of HIV-associated IRIS case definition) were compared with patients who remained IRIS free for at least 3 months. RESULTS: Twenty-six individuals with TB-IRIS and 64 without IRIS were included in the analysis. The median time to TB-IRIS was 14 days (interquartile range: 11-14 days). Univariate analysis showed that a positive pre-ART urinary LAM test [OR: 4.6 (95% CI: 1.5 to 13.8), P = 0.006] and a CD4 count <50 cells/mL [OR: 21 (95% CI: 2.6 to 169.4), P = 0.004] were associated with an increased risk of TB-IRIS. In multivariate analysis, only a baseline CD4 T-cell count <50 cells/mL was predictive of IRIS (P < 0.004). Sensitivity and specificity of a positive pre-ART urinary LAM test to diagnose IRIS were 80.8% (95% CI: 60.6 to 93.4) and 52.4% (95% CI: 39.4 to 65.1), respectively. CONCLUSIONS: If CD4 T-cell count testing is available, a pre-highly active antiretroviral therapy urinary LAM test has no added value to predict TB-IRIS. When CD4 T-cell count is not available, a positive LAM test could identify patients at increased risk of TB-IRIS.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Síndrome Inflamatória da Reconstituição Imune/etiologia , Lipopolissacarídeos/urina , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/urina , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Uganda
4.
Neurosignals ; 18(4): 203-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21135540

RESUMO

The NMDAR subunit NR3A is most highly expressed during the second postnatal week, when synaptogenesis reaches peak levels. Genetic ablation or overexpression of the NR3A subunit negatively interferes with the maturation of cortical synapses and leads to changes in the shape and number of dendritic spines, the density of which is increased in NR3A knock-out mice and decreased in NR3A-overexpressing transgenic mice. Alterations in spine density have been linked to dysregulation of mTOR signaling and synaptic protein translation. Using a yeast two-hybrid system, we identified the mTOR-activating GTPase Rheb as an interacting protein of the NMDAR subunit NR3A. We confirmed the interaction in mammalian cells by expressing recombinant Rheb and NR3A and showed that Rheb and NR3A could be co-immunoprecipitated from synaptic plasma membranes from the developing rat brain. These data suggest that NR3A sequesters synaptic Rheb and might thus function as a break of the mTOR-dependent synaptic translation of protein.


Assuntos
Proteínas Monoméricas de Ligação ao GTP/metabolismo , Neuropeptídeos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Química Encefálica/genética , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas Monoméricas de Ligação ao GTP/genética , Neuropeptídeos/genética , Proteína Enriquecida em Homólogo de Ras do Encéfalo , Ratos , Ratos Long-Evans , Receptores de N-Metil-D-Aspartato/genética , Transdução de Sinais/genética , Membranas Sinápticas/enzimologia , Membranas Sinápticas/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...