Dissociated functional recovery in parkinsonian monkeys following transplantation of astroglial cells.

Bilateral astroglial transplantation into the neostriatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys resulted in significant performance improvement in a spatial delayed response task, but failed to modify perseveration in an object retrieval detour task, or to improve motor clinical rating. Results suggest that brain circuits subserving various motor and cognitive performances can be functionally dissociated, and that remaining resources for the reorganization of neural circuits involved in spatial working memory performance in parkinsonian monkeys, appear to be responsive to striatal transplantation of subcultured, fetal striatal astroglial cells.

Aportes al conocimiento de los procesos de organización y reorganización en el sistema Nervioso Central / An attempt to the knowledge of the organizative and re-organizative processes of the Central nervous System

El conjunto de proyectos desarrollados en PRUNA se basan en la implementación de diferentes enfoques con el objetivo global de estudiar y analizar procesos de organización y reorganización en el sistema nervioso central, así como la participación de componentes no neuronales en los mismos y su posible implementación terapéutica en los procesos de reorganización luego del daño cerebral. Se ilustran tales aspectos comparando las distintas líneas experimentales desarrolladas en PRUNA: la difusión de factores tróficos que actúan modificando el fenotipo de diferentes procesos celulares y la provisión de señales para su organización; la modulación de información neural a través de procesos autocrínicos y paracrínicos; la expresión de moléculas específicas de distintas regiones corticales en función de variaciones amientales; la modulación de la respuesta astroglial ante procesos de lesión y su modulación por parte de factores tróficos; la funcionalidad de la astroglUa como prótesis biológica a transplantar; y el hallaazgo, la expresión, caracterrización citoarquitectónica y funcionamiento postlesional de componentes astrogliales específicos de la corteza cerebral de los primates. En síntesis, la naturaleza hterogénea de los componentes y funciones astrogliales implica tenerlos en consideración obligada para cualquier estudio del SNC que contemple su desarrollo en condiciones normales y patológicas

Aportes al conocimiento de los procesos de organización y reorganización en el sistema Nervioso Central / An attempt to the knowledge of the organizative and re-organizative processes of the Central nervous System

El conjunto de proyectos desarrollados en PRUNA se basan en la implementación de diferentes enfoques con el objetivo global de estudiar y analizar procesos de organización y reorganización en el sistema nervioso central, así como la participación de componentes no neuronales en los mismos y su posible implementación terapéutica en los procesos de reorganización luego del daño cerebral. Se ilustran tales aspectos comparando las distintas líneas experimentales desarrolladas en PRUNA: la difusión de factores tróficos que actúan modificando el fenotipo de diferentes procesos celulares y la provisión de señales para su organización; la modulación de información neural a través de procesos autocrínicos y paracrínicos; la expresión de moléculas específicas de distintas regiones corticales en función de variaciones amientales; la modulación de la respuesta astroglial ante procesos de lesión y su modulación por parte de factores tróficos; la funcionalidad de la astroglUa como prótesis biológica a transplantar; y el hallaazgo, la expresión, caracterrización citoarquitectónica y funcionamiento postlesional de componentes astrogliales específicos de la corteza cerebral de los primates. En síntesis, la naturaleza hterogénea de los componentes y funciones astrogliales implica tenerlos en consideración obligada para cualquier estudio del SNC que contemple su desarrollo en condiciones normales y patológicas

Disruption of patterns of immunoreactive glial fibrillary acidic protein processes in the Cebus Apella striate cortex following loss of visual input.

Long, interlaminar, astroglial processes and its patterned organization in the striate cortex of adult primates was previously described. Loss of visual input following bilateral retinal detachment and degeneration in an adult Cebus apella monkey resulted three months later in reduction of interlaminar processes immunoreactive to Glial Fibrillary Acid Protein antibody, loss of the honeycomb-like pattern normally present in tangential sections, and loss of high density patches of terminal segments of those processes in the opercular striate. These results further indicate the highly interactive nature of neuron-glial cerebral cortex architecture, and the dynamic regulation of astroglial interlaminar processes.

Astroglial interlaminar processes in the cerebral cortex of prosimians and Old World monkeys.

Previous observations have shown that astrocytes with interlaminar processes are present in the cerebral cortex of humans and New and Old World monkeys, but not in the rodent. The present report furthers the analysis of possible evolutionary aspects regarding the expression of such astroglial features. A comparison between young and adult Microcebus murinus, a prosimian, and Old World monkeys (Macaca mulatta and Papio hamadryas) is presented. Brain samples were processed for glial fibrillary acidic protein (GFAP), vimentin, MAP2 and SMI 311 immunocytochemistry, using different procedures. The cerebral cortex of adult Microcebus showed the presence of long astroglial processes, albeit reduced in number and length with respect to those observed in Old World monkeys. Macaca and Papio showed dense packing of such processes extending in most cortical regions to a depth of approximately 700 micrometers. Based on double immunolabelling for GFAP and MAP 2 antigens, the location and extent of these processes was shown to overlap with areas traversed by bundles and individual apical dendrites. Aged Old World specimens depicted an increased thickness of terminal portions of interlaminar processes, with increased morphological alterations. Comparisons made between the average thickness of the "brush" composed of interlaminar processes and the thickness of lamina I among the species analyzed disclosed an absence of relationship between them. This suggests that interlaminar processes do not represent cellular adaptations to the increase in thickness in superficial cortical laminae, but rather to some other evolutionary pressure. Since astroglial interlaminar processes are already present in a prosimian, although in a comparatively reduced manner, it is suggested that such processes underwent an early expression within the primate order, with increasing presence in more recent primate species.

Interlaminar astroglial processes in the cerebral cortex of non human primates: response to injury.

At variance with the rodent, presence of long glial fibrillary acid protein-immunoreactive (GFAP-IR) astroglial processes traversing several cortical laminae (interlaminar processes) appears to be characteristic of the primate cerebral cortex. Their permanence or changes may constitute a significant factor in the functional alterations that develop after brain injury. The immediate and long term response of such astroglial processes to local application of KCl or lesioning, respectively, was analyzed in the striate cortex of adult Cebus apella monkeys. Intraparenchymal injection of 5 mM (within physiological range) or 50 mM (injury levels) KCl into the striate cortex of Cebus apella monkeys resulted three hours later in increased GFAP immunoreactivity in astroglial cells and processes, in the development of numerous foldings and thickenings of GFAP-IR filaments, as compared to mechanical lesioning alone. Such changes were not observed in a cortical region that approximately included laminae IV and V. These results suggest that the immediate GFAP-IR response to KCl cannot be solely explained on the basis of an exposure of new GFAP epitopes due to conformational changes following K-induced cell oedema, or to disaggregation of such filaments. Three months after mechanical lesioning of the frontal and striate cortex, interlaminar processes were absent up to 1.0 mm from the lesion site, and a predominant astrocytosis was present. Long term effects of mechanical lesioning on interlaminar processes resulted in a persistent reduction of these long processes in the vicinity of the lesion, suggesting a significant and prolonged alteration of the astroglial architecture in the adult primate cerebral cortex. It is speculated that these astroglial changes may bear a relationship with the functional alterations observed during the recovery process after brain injury.

Postnatal development of interlaminar astroglial processes in the cerebral cortex of primates.

UNLABELLED: Long astroglial processes traversing several cortical laminae appear to be characteristic of primate brains. Whether interlaminar processes develop as a modification of radial glia or are truly postnatal elements stemming from stellate astroglia, could be assessed by analyzing their early developmental stages. A survey of glial fibrillar acidic protein immunoreactive (GFAP-IR) astroglial interlaminar processes in the cerebral cortex of Ceboidea monkeys at various postnatal developmental ages, and in human cortical samples of a ten day and a seven year old child disclosed that such processes develop postnatally. At one month of age GFAP-IR interlaminar processes in monkeys were scarce and short in most frontal, parietal or occipital (striate) cortical areas, except for sulcal (principal and orbital sulci) and temporal cortical areas. Some processes were weakly positive for vimentin, and these were most abundant in ventral temporal cortical areas. At two months of age processes were present in all these areas, albeit in restricted patches and significantly shorter than in adults. The expression of this pattern was increased at seven months of age. At three years of age almost every area showed abundant processes and with lengths comparable to the adult Ceboidea individuals. In humans, at 10 days of age long interlaminar processes were readily apparent in a frontal cortex sample, becoming most apparent at the age of seven years although not reaching yet the adult characteristics as described previously. CONCLUSIONS: (1) GFAP-IR interlaminar processes develop postnatally, thus typifying a subtype of the classical stellate forms; (2) they bear no obvious direct relationship with radial glia; (3) their development is not contemporary among the various cortical regions. These long cellular processes represent an addition to those already described for other astroglial cell types in the adult mammalian brain (Golgi-Bergmann glia, tanicytes, Muller cells).

Long, interlaminar astroglial cell processes in the cortex of adult monkeys.

At variance with current descriptions stressing the stellate geometry of cortical astrocytes in the brain of adult mammals, GFAP-immunoreactive astrocytes from prefrontal and rostral cingulate cortices in two adult New World monkey species, Cebus apella and Saimiri sciureus, were found to have long cellular processes traversing several cortical lamina. These unreported features of cortical astroglial cells in adult nonhuman primates pose new issues for the understanding of iso- and allocortical organization and processing in higher mammals.