Effects of infantile/prepubertal chronic estrogen treatment and chemical sympathectomy with guanethidine on developing cholinergic nerves of the rat uterus.

The innervation of the uterus is remarkable in that it exhibits physiological changes in response to altered levels in the circulating levels of sex hormones. Previous studies by our group showed that chronic administration of estrogen to rats during the infantile/prepubertal period provoked, at 28 days of age, an almost complete loss of norepinephrine-labeled sympathetic nerves, similar to that observed in late pregnancy. It is not known, however, whether early exposure to estrogen affects uterine cholinergic nerves. Similarly, it is not known to what extent development and estrogen-induced responses in the uterine cholinergic innervation are affected by the absence of sympathetic nerves. To address this question, in this study we analyzed the effects of infantile/prepubertal chronic estrogen treatment, chronic chemical sympathectomy with guanethidine, and combined sympathectomy and chronic estrogen treatment on developing cholinergic nerves of the rat uterus. Cholinergic nerves were visualized using a combination of acetylcholinesterase histochemistry and the immunohistochemical demonstration of the vesicular acetylcholine transporter (VAChT). After chronic estrogen treatment, a well-developed plexus of cholinergic nerves was observed in the uterus. Quantitative studies showed that chronic exposure to estrogen induced contrasting responses in uterine cholinergic nerves, increasing the density of large and medium-sized nerve bundles and reducing the intercept density of fine fibers providing myometrial and perivascular innervation. Estrogen-induced changes in the uterine cholinergic innervation did not appear to result from the absence/impairment of sympathetic nerves, because sympathectomy did not mimic the effects produced by estrogen. Estrogen-induced responses in parasympathetic nerves are discussed, considering the direct effects of estrogen on neurons and on changes in neuron-target interactions.

Plasticity in rat uterine sympathetic nerves: the role of TrkA and p75 nerve growth factor receptors.

Uterine sympathetic innervation undergoes profound remodelling in response to physiological and experimental changes in the circulating levels of sex hormones. It is not known, however, whether this plasticity results from changes in the innervating neurons, the neuritogenic properties of the target tissue or both. Using densitometric immunohistochemistry, we analysed the effects of prepubertal chronic oestrogen treatment (three subcutaneous injections of 20 microg of beta-oestradiol 17-cypionate on days 25, 27 and 29 after birth), natural peripubertal transition and late pregnancy (19-20 days post coitum) on the levels of TrkA and p75 nerve growth factor receptors in uterine-projecting sympathetic neurons of the thoraco-lumbar paravertebral sympathetic chain (T7-L2) identified using the retrograde tracer Fluorogold. For comparative purposes, levels of TrkA and p75 were assessed in the superior cervical ganglion (SCG) following prepubertal chronic oestrogen treatment. These studies showed that the vast majority of uterine-projecting neurons expressed both TrkA and p75. Both prepubertal chronic oestrogen treatment and the peripubertal transition increased the ratio p75 to TrkA in uterine-projecting neurons, whereas pregnancy elicited the opposite effect. Prepubertal chronic oestrogen treatment had no effects on levels of TrkA or p75 in sympathetic neurons of the SCG. Taken together, our data suggest that neurotrophin receptor-mediated events may contribute to regulate sex hormone-induced plasticity in uterine sympathetic nerves, and are in line with the idea that, in vivo, plasticity in uterine nerves involves changes in both the target and the innervating neurons.

Alteraciones histopatológicas del epitelio nasal en pacientes respiratorios crónicos / Histopathologic alterations of nasal epithelium in chronic respiratory patients

El revestimiento epitelial de las vías respiratorias, conjuntamente con el transporte mucociliar, forman parte de la primera línea de defensa del aparato respiratorio. Las condiciones que alteran la integridad epitelial o afectan la eficiencia del transportemucociliar conducen o favorecen la recurrencia de la enfermedad respiratoria. En el presente trabajo reportamos los resultados obtenidos del estudio por histología de alta resolución y microscopía electrónica de barrido del epitelio nasal de 33 pacientes respiratorios crónicos. Todos las biopsias de cornete inferior analizadas presentaron algún tipo de anomalía epitelial, no detectándose en ningún caso el epitelio seudoestratificado cilíndrico ciliado que normalmente reviste las vías respiratorias. En 17 de los 33 pacientes se reconocieron epitelios ciliados con distintos grados de atipía, mientras que en los 16 restantes se observó la sustitución total de las células ciliadas por tipos celulares no ciliados, tales como células basales, células caliciformes y células escamosas. En 27 por ciento de los casos las alteraciones epiteliales del cornete inferior se presentaron en pacientes que portaban afecciones ciliares primarias, mientras que en 52 por ciento se presentaron en pacientes que mostraban alteraciones ciliares inespecíficas o ausencia de cilias. En 21 por ciento de los casos se detectaron afecciones epiteliales en pacientes que tenían una ultraestructura ciliar normal. Los datos obtenidos confirman el concepto de que las alteraciones epiteliales pueden presentarse a consecuencia de los desórdenes ciliares primarios o secundarios, y resultar también de la injuria prolongada provocada por diversas enfermedades respiratorias crónicas, tales como neumonías, bronquitis, rinitis, sinusitis y asma. Dado que la inflamación e infección respiratoria recurrente retrasa la regeneración del epitelio normal, la detección precoz de estas alteraciones histopatológicas epiteliales y sus afecciones ciliares asociadas es clave para evitar la instalación de formas epiteliales no ciliadas irreversibles.