RESUMEN
The mechanisms underlying neurotrophin dependence, and cellular dependent states in general, are unknown. We show that a 29 amino acid region in the intracellular domain of the common neurotrophin receptor, p75NTR, is required for the mediation of apoptosis by p75NTR. Furthermore, contrary to results obtained with Fas, monomeric p75NTR is required for apoptosis induction, whereas multimerization inhibits the pro-apoptotic effect. Within the 29-residue domain required for apoptosis induction by p75NTR, a 14-residue region is sufficient as a peptide inducer of apoptosis. This 14-residue peptide requires the positively charged carboxyterminal residues for its effect on cell death, and these same residues are required by the full-length p75NTR. These studies define a novel type of domain that mediates neurotrophin dependence, and suggest that other cellular dependent states may be mediated by proteins displaying similar domains.
Asunto(s)
Apoptosis/genética , Receptor de Factor de Crecimiento Nervioso/química , Receptor de Factor de Crecimiento Nervioso/metabolismo , Secuencia de Aminoácidos/genética , Animales , Sistema Libre de Células/metabolismo , Dimerización , Vectores Genéticos/genética , Humanos , Mutación/genética , Fragmentos de Péptidos/genética , Plásmidos/biosíntesis , Plásmidos/genética , Estructura Terciaria de Proteína/genética , Receptor de Factor de Crecimiento Nervioso/genética , Proteínas Recombinantes de Fusión/genética , Transfección , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/metabolismoRESUMEN
This report offers a description of typical changes seen on gadolinium-enhanced magnetic resonance (MR) imaging of the entire spine that indicate spontaneous intracranial hypotension (SIH). To the authors' knowledge, this is the first report of its kind. They describe three cases of SIH that were accompanied by dural enhancement throughout the neuraxis on imaging, with the evolution of associated subdural and epidural fluid collections in the spine. Recognition of this disorder is important to be able to distinguish it from an infectious or neoplastic process in which surgical intervention might be warranted. Evaluation using gadolinium-enhanced cranial and spinal MR imaging in patients with postural headaches and an (111)In-labeled cerebrospinal fluid leak study are discussed. Treatment with an epidural blood patch is shown to be particularly effective, with resolution of the radiological and clinical findings.
Asunto(s)
Duramadre/patología , Aumento de la Imagen , Hipotensión Intracraneal/diagnóstico , Imagen por Resonancia Magnética , Adulto , Infecciones Bacterianas/diagnóstico , Parche de Sangre Epidural , Líquido Cefalorraquídeo , Medios de Contraste , Diagnóstico Diferencial , Duramadre/diagnóstico por imagen , Espacio Epidural/diagnóstico por imagen , Espacio Epidural/patología , Estudios de Evaluación como Asunto , Femenino , Gadolinio , Cefalea/diagnóstico , Humanos , Radioisótopos de Indio , Hipotensión Intracraneal/diagnóstico por imagen , Hipotensión Intracraneal/terapia , Postura , Cintigrafía , Radiofármacos , Neoplasias de la Médula Espinal/diagnóstico , Efusión Subdural/diagnóstico , Efusión Subdural/diagnóstico por imagen , Resultado del TratamientoRESUMEN
The neuropoietic cytokine leukemia inhibitory factor (LIF) can act as a trophic factor, enhancing neuronal survival, and as a differentiation factor altering neuronal and glial gene expression. LIF also plays a role in the response to injury of the peripheral nervous system, as indicated by an increase in the amount of its mRNA within nonneuronal injury response in LIF knock-out mice. To determine if LIF is regulated after injury to the central nervous system, we surgically lesioned the cortex in adult rat brain. Using a quantitative RNAse protection assay, we find that LIF mRNA increases 30-fold following injury. The amount of this transcript goes up within 6 h after injury, reaches a peak at 24 h and returns to baseline by 7 days postlesion. In situ hybridization analysis reveals LIF transcript-containing cells scattered throughout the ipsilateral cortex close, but not immediately adjacent to the lesion site. Double-labeling with a variety of antibodies reveals that LIF mRNA is induced in GFAP-positive astrocytes as well as in a small number of microglial cells. The striking induction of LIF transcripts in glia suggests that this cytokine may play a key injury-response role in the CNS as it does in the PNS, where LIF has been demonstrated to regulate neuropeptide expression both in vivo and in vitro.
Asunto(s)
Astrocitos/metabolismo , Lesiones Encefálicas/metabolismo , Inhibidores de Crecimiento/metabolismo , Interleucina-6 , Linfocinas/metabolismo , Animales , Lesiones Encefálicas/patología , Corteza Cerebral/lesiones , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Femenino , Lateralidad Funcional , Inhibidores de Crecimiento/genética , Hibridación in Situ , Factor Inhibidor de Leucemia , Linfocinas/genética , Microglía/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Basal lamina-rich extracts of Torpedo californica electric organ contain a factor that causes acetylcholine receptors (AChRs) on cultured myotubes to aggregate into patches. Our previous studies have indicated that the active component of these extracts is similar to the molecules in the basal lamina which direct the aggregation of AChRs in the muscle fibre plasma membrane at regenerating neuromuscular junctions in vivo. Because it can be obtained in large amounts and assayed in controlled conditions in cell culture, the AChR-aggregating factor from electric organ may be especially useful for examining in detail how the postsynaptic apparatus of regenerating muscle is assembled. Here we demonstrate that the electric organ factor causes not only the formation of AChR aggregates on cultured myotubes, but also the formation of patches of acetylcholinesterase (AChE). This finding, together with the observation that basal lamina directs the formation of both AChR and AChE aggregates at regenerating neuromuscular junctions in vivo, leads us to hypothesize that a single component of the synaptic basal lamina causes the formation of both these synaptic specializations on regenerating myofibres.