RESUMEN
Microglia are cells of myeloid origin that populate the CNS during early development and form the brain's innate immune cell type. They perform homoeostatic activity in the normal CNS, a function associated with high motility of their ramified processes and their constant phagocytic clearance of cell debris. This debris clearance role is amplified in CNS injury, where there is frank loss of tissue and recruitment of microglia to the injured area. Recent evidence suggests that this phagocytic clearance following injury is more than simply tidying up, but instead plays a fundamental role in facilitating the reorganization of neuronal circuits and triggering repair. Insufficient clearance by microglia, prevalent in several neurodegenerative diseases and declining with ageing, is associated with an inadequate regenerative response. Thus, understanding the mechanism and functional significance of microglial-mediated clearance of tissue debris following injury may open up exciting new therapeutic avenues.
Asunto(s)
Encéfalo/patología , Microglía/fisiología , Regeneración Nerviosa/fisiología , Enfermedades Neurodegenerativas/patología , Envejecimiento/inmunología , Encéfalo/inmunología , Citocinas/inmunología , Humanos , Enfermedades Neurodegenerativas/inmunología , Fagocitosis/fisiologíaRESUMEN
Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling, demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries.
Asunto(s)
Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Hidrolasas Diéster Fosfóricas/metabolismo , Pirofosfatasas/metabolismo , Animales , Células COS , Chlorocebus aethiops , Cartilla de ADN , Femenino , Técnica del Anticuerpo Fluorescente , Inmunohistoquímica , Hibridación in Situ , Lisofosfolípidos/biosíntesis , Masculino , Neuroglía/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Much interest has been drawn to the investigation of the hypothalamic-pituitary-thyroid (HPT)-axis in patients suffering from depression or panic disorder. However, there is no data concerning agoraphobia. METHODS: Patients with panic disorder, agoraphobia, major depression were compared to normal controls (total n=88) in respect to HPT axis, obtaining basal TSH and administering a TRH test. RESULTS: Normal controls and agoraphobics showed significantly higher Delta(max) TSH than depressives and panic patients. There were no differences between agoraphobics and normal controls. CONCLUSIONS: Agoraphobia, unlike depression or panic disorder, seems to be less biologically determined in respect to the HPT-axis.
Asunto(s)
Agorafobia/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Sistema Hipotálamo-Hipofisario/fisiopatología , Trastorno de Pánico/fisiopatología , Glándula Tiroides/fisiopatología , Adulto , Agorafobia/diagnóstico , Agorafobia/psicología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Trastorno de Pánico/diagnóstico , Trastorno de Pánico/psicología , Valores de Referencia , Sensibilidad y Especificidad , Tirotropina/sangre , Hormona Liberadora de TirotropinaRESUMEN
An association between macrophages and remyelination efficiency has been observed in a variety of different models of CNS demyelination. In order to test whether this association is causal or coincidental, we have examined the effects of macrophage depletion on the rate of remyelination of lysolecithin-induced demyelination in the spinal cord of young adult female rats. Macrophage depletion was achieved by reducing the monocyte contribution to the macrophages within the lesion using the clodronate-liposome technique. This technique not only resulted in a decrease in Ox-42-positive cells in the spleen of treated animals but also in the levels of macrophage scavenger receptor type B mRNA expression within the demyelinating lesion. In animals treated with clodronate-liposomes throughout the remyelination process, there was a significant decrease in the extent of oligodendrocyte remyelination at 3 weeks after lesion induction, but no effect on Schwann cell remyelination. If macrophage depletion was delayed until the second half of the remyelination phase, then there was no effect on the repair outcome, implying that macrophages are required for the early stages of CNS remyelination. The results of this study indicate that the macrophage response is an important component of successful CNS remyelination and that approaches to the treatment of demyelinating disease based on inhibition of the inflammatory response may also impair regenerative events that follow demyelination.