Morfología neuronal en el trastorno del espectro autista / Neuronal morphology in autism spectrum disorder

RESUMEN: El trastorno del espectro autista (TEA) abarca un grupo de trastornos multifactoriales del neurodesarrollo caracterizados por una comunicación e interacción social deteriorada y por comportamientos repetitivos y estereotipados. Múltiples estudios han revelado que en el TEA existen disfunciones sinápticas, en la cual la morfología y función neuronal son sustratos importantes en esta patogenia. En esta revisión comentamos los datos disponibles a nivel de anormalidades neuronales en el TEA, enfatizando la morfología de las dendritas, espinas dendríticas y citoesquelo de actina. Las dendritas y espinas dendríticas, ricas en actina, forman la parte postsináptica de la mayoría de las sinapsis excitadoras. En el TEA, los datos obtenidos apuntan a una desregulación en el crecimiento y desarrollo dendrítico, así como una alteración en la densidad de las espinas dendríticas. Lo anterior, se ve acompañado de alteraciones en la remodelación y composición del citoesqueleto neuronal. Para comprender mejor la fisiopatología del TEA, es necesario mayor información sobre cómo los cambios morfofuncionales de los actores que participan en la sinapsis impactan en los circuitos y el comportamiento.

SUMMARY: Autism Spectrum Disorder (ASD) is a group of multifactorial neurodevelopmental disorders, characterized by impaired communication and social interaction skills, and by repetitive and stereotyped behaviors. Multiple studies report that there are synaptic dysfunctions in ASD, in which important substrates such as morphology and neuronal function are involved in this pathogenesis. In this review we discuss the data available at the level of neuronal abnormalities in ASD, and emphasize the morphological aspects of dendrites, dendritic spines, and actin cytoskeleton. Actin-rich dendrites and dendritic spines shape the postsynaptic part of the most excitatory synapses. In ASD, the data points to a dysregulation in dendritic growth and development, as well as an alteration in the density of dendritic spines. This is accompanied by alterations in the remodeling and composition of the neuronal cytoskeleton. In order to better understand the pathophysiology of ASD, further information is needed on how the elements of synaptic morphofunctional changes impact circuits and behavior.

Retracción a largo plazo del árbol dendrítico de neuronas piramidales córtico-faciales por lesiones periféricas del nervio facial / Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons

Introducción. Poco se sabe sobre las modificaciones morfológicas de las neuronas de la corteza motora tras lesiones en nervios periféricos, y de la implicancia de dichos cambios en la recuperación funcional tras la lesión. Objetivo. Caracterizar en ratas el efecto de la lesión del nervio facial sobre la morfología de las neuronas piramidales de la capa V de la corteza motora primaria contralateral. Materiales y métodos. Se reconstruyeron neuronas piramidales teñidas con la técnica de Golgi-Cox, de animales control (sin lesión) y animales con lesiones y sacrificados a distintos tiempos luego de la lesión. Se utilizaron cuatro grupos: sham (control), lesión 1S, lesión 3S y lesión 5S (animales con lesiones y evaluados 1, 3 y 5 semanas después de la lesión irreversible del nervio facial, respectivamente). Se evaluaron mediante el análisis de Sholl, las ramificaciones dendríticas de las células piramidales de la corteza motora contralateral a la lesión. Resultados. Los animales con lesiones presentaron parálisis completa de las vibrisas mayores durante las cinco semanas de observación. Comparadas con neuronas de animales sin lesiones, las células piramidales córtico-faciales de los lesionados mostraron una disminución significativa de sus ramificaciones dendríticas. Esta disminución se mantuvo hasta cinco semanas después de la lesión. Conclusiones. Las lesiones irreversibles de los axones de las motoneuronas del núcleo facial, provocan una retracción sostenida del árbol dendrítico en las neuronas piramidales córtico-faciales. Esta reorganización morfológica cortical persistente podría ser el sustrato fisiopatológico de algunas de las secuelas funcionales que se observan en los pacientes con parálisis facial periférica.

Introduction. Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Objective. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Materials and methods. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Results. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the fiveweek observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Discussion. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

Subicular lesion induced impairment in operant behaviour and altered dendritic morphology of CA1, CA3 hippocampal neurons.

The effects of bilateral electrolytic subicular lesions were examined on the operant behaviour for food reward on a continuous reinforcement schedule as well as the dendritic morphology of CA1 and CA3 hippocampal areas. The subjects were female Wistar rats 20 days of age and were divided into four groups. 1. Age matched control 2. Sham operated 3. Operant behaviour for food reward and 4. Subicular lesion. Animals were starved twenty-four hours prior to operant behaviour training sessions. Two trial sessions with continuous reinforcement (CRF) of 10 min duration/day were done during training sessions following which the rats were allowed CRF for ten minutes per day for ten days. On the eleventh day, the operant behaviour and sham operated animals were taken up for bilateral subicular lesion and sham surgery respectively. After seventy two hours of surgical recovery, operant behavioural testing was done as before for a further period of ten days. Later all the groups of animals were sacrificed and the hippocampi were processed for rapid Golgi staining technique. Our results suggest that subicular lesions do produce a significant reduction in operant learning behaviour for food reward. Further the Golgi studies revealed a reduction in dendritic branching points and intersections of apical and basal CA1, CA3 neurons in lesioned animals.