RESUMEN
Stroke is the third most common cause of mortality and the leading cause of disability in industrialized country. According to population based-studies, ischemic stroke accounts for 67-80% of all strokes. Thrombolysis is used during the acute phase in only 2-5% of ischemic patients. Clinical trials of candidate neuroprotective agents have failed to identify viable therapies for ischemic stroke in humans. There is therefore a great need for new therapeutic strategies, considering that not all brain cells die immediately after ischemic stroke.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Purinas/farmacología , Purinas/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Humanos , Modelos Biológicos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , RoscovitinaRESUMEN
This study has provided evidence for the natural occurrence of sandflies in Germany. Two species belonging to the genus Phlebotomus were detected. Phlebotomus (Larroussius) perniciosus, a proven vector of leishmaniasis, was found in association with an autochthonous case of canine leishmaniasis near Kaiserslautern. Two hundred thirty-seven specimens of Phlebotomus (Transphlebotomus) mascittii were caught in 17 different locations in Baden-Wuerttemberg and Rhineland-Palatinate. The northernmost finding in Germany (and Europe) was near Cochem (Moselle). P. mascittii has not yet been confirmed as a vector of leishmaniasis, but its competence is strongly suspected. In addition to the detection of the vector, since 1991, there have been 11 cases of leishmaniasis in Germany in which an autochthonous origin was confirmed or which were highly likely to have been of indigenous origin. Data from the German meteorological service indicate that Germany currently has a Mediterranean climate, with an annual average temperature of 10 degrees C being reached or exceeded in several regions. This type of climate is also appropriate for the living conditions of sandflies. Therefore, it is assumed that sandflies have a greater geographical distribution in Germany than the first studies suggested, being mainly restricted to the southern region of Baden-Wuerttemberg. The risk of an autochthonous canine infection occurring in Germany is very low. The rapidly increasing number of imported cases of leishmaniasis in dogs means that special attention must be focused on veterinary advice to dog owners about prophylaxis. The results indicate that the use of repellents and preventive behavioural measures is vital.
Asunto(s)
Vectores de Enfermedades , Enfermedades de los Perros/epidemiología , Leishmaniasis/veterinaria , Phlebotomus/parasitología , Animales , Clima , Control de Enfermedades Transmisibles/métodos , Enfermedades de los Perros/parasitología , Perros , Alemania/epidemiología , Leishmaniasis/epidemiología , Leishmaniasis/transmisiónRESUMEN
In the first week of February 2008 on the island of Corsica, 55 Phlebotomus (Transphlebotomus) mascittii, 39 males and 16 females, were caught in a railway tunnel. This is the first proof of the winter activity of the adult P. mascittii in Europe.
Asunto(s)
Phlebotomus/fisiología , Estaciones del Año , Animales , Ecología , Femenino , Francia , Masculino , Phlebotomus/clasificación , TemperaturaRESUMEN
The TrkC subfamily of primary high-affinity neurotrophin-3 receptors is composed of catalytic (kinase-containing; TrkC K) and noncatalytic (TrkC NC) isoforms generated by alternative splicing. We previously reported the presence of the mouse noncatalytic TrkC NC2 isoform in regions of neuronal differentiation [Menn, B., Timsit, S., Calothy, G. & Lamballe, F. (1998) J. Comp. Neurol., 401, 47-64]. In order to gain insight into specific roles for TrkC NC2 receptors during CNS neurogenesis, we compared its distribution with that of its catalytic counterparts and the p75NTR receptor in in vivo and in vitro model systems of early and late neuronal differentiation. We found that TrkC NC2 expression coincided with the exit of neuronal progenitors from the cell cycle and was maintained in differentiated cerebellar neurons. We also showed that, whilst TrkC K receptors were expressed both in mitotic and postmitotic cells, TrkC NC2 was present only in differentiating neural stem cell progeny, suggesting its involvement in neuronal and glial cell differentiation. During neuritogenesis of primary neocortical neurons, both TrkC isoforms as well as p75NTR were located in axonal and dendritic processes. However, whilst these various receptors were present in the same neuronal compartments, TrkC NC2 distribution was specifically restricted to distinct areas of extending neurites. Taken together, these findings suggest that spatiotemporal localization of the noncatalytic receptor could account for specific local effects of neurotrophin-3.
Asunto(s)
Neocórtex/química , Neocórtex/embriología , Receptor de Factor de Crecimiento Nervioso/genética , Receptor trkC/genética , Animales , Axones/química , Axones/enzimología , Dominio Catalítico/fisiología , Diferenciación Celular/fisiología , Células Cultivadas , Cerebelo/química , Cerebelo/embriología , Cerebelo/enzimología , Técnica del Anticuerpo Fluorescente , Regulación del Desarrollo de la Expresión Génica , Conos de Crecimiento/química , Conos de Crecimiento/enzimología , Isomerismo , Ratones , Ratones Endogámicos C57BL , Mitosis/fisiología , Neocórtex/enzimología , Neuroglía/química , Neuroglía/citología , Neuroglía/enzimología , Neuronas/química , Neuronas/enzimología , Neuronas/ultraestructura , ARN Mensajero/análisis , Ratas , Ratas Wistar , Receptor de Factor de Crecimiento Nervioso/análisis , Receptor trkC/análisis , Receptor trkC/química , Células Madre/química , Células Madre/citología , Células Madre/enzimologíaRESUMEN
Acidic calponin, an F-actin-binding protein, is particularly enriched in brain, where calponin protein and mRNA are mainly expressed by neurons. The presence of calponin immunoreactivity in cultured astroglial cells has been reported, but the presence of acidic calponin in astrocytes in vivo appears equivocal. For the present study, we raised a specific polyclonal antibody against the 16-residue synthetic peptide covering the sequence E311-Q326 (EYPDEYPREYQYGDDQ) situated at the carboxy-terminal end of rat acidic calponin, and we investigated the cellular and subcellular localization of the protein in the developing central nervous system. Our results show that acidic calponin is particularly enriched in: (i) growth cones and submembranous fields of maturing cerebellar and cortical cells, where it codistributes with microfilaments and (ii) glial cells in vivo, including radial glia, glia limitans, Bergmann glia and mature astrocytes, and ex vivo, where acidic calponin strongly colocalizes with intermediate glial fibrillary acidic protein (GFAP) and vimentin filaments. Finally, up to four acidic calponin subtypes with different isoelectric point (pI) values were identified by two-dimensional gel electrophoresis of cerebellar and hippocampal extracts. The more acidic isoforms were developmentally regulated. As only one single mRNA for acidic calponin has been identified, these isoforms must reflect postsynthesis changes probably related to the particular functions of acidic calponin in maturing cells. Although brain acidic calponin's exact role remains uncertain, the present data suggest that it is involved in neuronal and glial plasticity.
Asunto(s)
Ácidos/metabolismo , Animales Recién Nacidos/metabolismo , Encéfalo/metabolismo , Proteínas de Unión al Calcio/metabolismo , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Envejecimiento/metabolismo , Animales , Biomarcadores , Encéfalo/citología , Encéfalo/crecimiento & desarrollo , Membrana Celular/metabolismo , Células Cultivadas , Conos de Crecimiento/metabolismo , Inmunohistoquímica , Filamentos Intermedios/metabolismo , Proteínas de Microfilamentos , Neuroglía/metabolismo , Ratas , Fracciones Subcelulares/metabolismo , Distribución Tisular/fisiología , CalponinasRESUMEN
Members of the trk gene family encode neurotrophin receptors. The trkC locus encodes multiple neurotrophin-3 catalytic and noncatalytic receptor isoforms. We report the molecular cloning and characterization of mouse cDNAs encoding two noncatalytic TrkC receptors: novel isoforms designated as TrkC NC1 and TrkC NC2, the mouse homologue of the TrkC truncated form previously identified in rat (Tsoulfas et al. [1993] Neuron 10:975-990; Valenzuela et al. [1993] Neuron 10:963-974). We extensively analyzed the transcription pattern of these two noncatalytic isoforms and that of the catalytic isoforms by Northern blotting and in situ hybridization. We did not detect trkC NC1 transcripts in embryos, but we found that trkC NC1 expression is restricted to specific areas in adult brain. In contrast, trkC NC2 transcripts are readily detected early during embryogenesis and are expressed predominantly in adult brain and gonads. We also provide the first evidence for the existence of TrkC NC2 protein by using polyclonal antibodies that specifically recognize this isoform. By using in situ hybridization, we show for the first time that trkC NC2 transcripts are found in differentiating fields of maturing neurons and in mature neurons of laminar structures of adult brain. We also report a similarity of localization between trkC NC2 transcripts and markers of oligodendrocyte progenitors in the embryonic spinal cord. Furthermore, our results also show that trkC NC2 and trkC catalytic transcripts could be either codistributed (in the central and peripheral nervous system) or independently expressed, especially outside the nervous system. These results suggest that the TrkC NC2 isoform acts either independently or in association with its catalytic counterpart. Finally, we show that TrkC NC2 is expressed in dendrites of pyramidal neurons of hippocampus and cerebral cortex. We propose that this receptor is involved in proliferation of oligodendrocyte progenitors, neuronal differentiation, and synaptic plasticity and that it may also play a fundamental role in mediating neurotrophin-3 effects outside the nervous system.