Disruption of astroglial interlaminar processes in Alzheimer's disease.

A palisade of long, interlaminar astroglial processes in supragranular layers of the cerebral cortex is characteristic of adult individuals of anthropoid species. In the present study, this distinctive cytoarchitectonic feature was analyzed in tissue deriving from the neocortex of cases affected by Alzheimer's disease (n=14) and age-matched control cases (n=10). Samples of different cortical areas, and in particular prefrontal, temporal and striate fields, were analyzed. Astroglia was labeled by glial fibrillary acidic protein immunoreactivity, that allowed a clear distinction between the classical, stellate intralaminar astroglia and the interlaminar glial processes. The occurrence and relative density of neuritic plaques were ascertained in the same specimens with Bielchowsky staining. In most cortical regions of cases diagnosed as severe Alzheimer's disease by the donor institutions, interlaminar astroglia was found to be markedly altered or absent, and replaced by hypertrophic intralaminar astrocytes. Cases diagnosed as milder or uncertain Alzheimer's disease showed a less consistent involvement of the interlaminar glial palisade. Alterations of the interlaminar palisade in the cortex affected by Alzheimer's disease did not strictly correlate with the density of neuritic plaques in the examined specimens. The findings indicate that loss/severe disruption of the interlaminar palisade of astroglial processes is part of the array of neuropathological changes occurring in the cerebral cortex during Alzheimer's disease. In addition, our data indicate that different types of neocortical astrocytes (namely intralaminar and interlaminar astrocytes) respond differently to the pathobiology of Alzheimer's disease in the neocortex, inasmuch as interlaminar processes tend to disappear while intralaminar processes become reactive.

Reduced whole-body fat oxidation in women and in the elderly.

OBJECTIVE: To test the hypothesis that the increase in fat mass observed with aging might be related to a decrease in whole-body fat oxidation. SUBJECTS AND MEASUREMENTS: Forty volunteers had measurements of sleeping and 24 h substrate oxidation in calorimetric chambers, body composition with the (18)O dilution technique, VO(2)max, and fiber composition analysis from a biopsy of vastus lateralis. They were divided into 10 young women, 10 young men, 10 elderly women and 10 elderly men. RESULTS: Sleeping fat oxidation and 24 h fat oxidation were lower in women than in men and in elderly than in young participants. Sleeping fat oxidation was correlated to fat-free mass and energy balance (multivariate analysis). Twenty four hour fat oxidation was correlated to total energy expenditure and energy balance (multivariate analysis). After adjustment for differences in these factors, sleeping and 24 h fat oxidation were no longer different between age and sex groups. None of the parameters of macronutrient metabolism was correlated with muscle fiber composition. CONCLUSION: Our data suggest that fat oxidation is lower in elderly subjects. This difference could favour fat mass gain if fat intake is not adequately reduced. Differences in fat-free mass and in total energy expenditure appear to participate in the reduction in fat oxidation. International Journal of Obesity (2001) 25, 39-44

"Rodent-like" and "primate-like" types of astroglial architecture in the adult cerebral cortex of mammals: a comparative study.

Previous observations disclosed that astroglia with interlaminar processes were present in the cerebral cortex of adult New and Old World monkeys, but not in the rat, and scarcely in the prosimian Microcebus murinus. The present report is a more systematic and comprehensive comparative analysis of the occurrence of such processes in the cerebral cortex of several mammalian species. Brain samples were obtained from adult individuals from the following orders: Carnivora (canine), Rodentia (rat and mouse), Marsupialia (Macropus eugenii), Artiodactyl (bovine and ovine), Scandentia (Tupaia glis), Chiroptera (Cynopteris horsfieldii and C. brachyotis), and Primate: Prosimian (Eulemur fulvus), non-human primate species (Cebus apella, Saimiri boliviensis, Callithrix, Macaca mulatta, Papio hamadryas, Macaca fascicularis, Cercopithecus campbelli and C. ascanius) and from a human autopsy. Tissues were processed for immunocytochemistry using several antibodies directed against glial fibrillary acidic protein (GFAP), with or without additional procedures aimed at the retrieval of antigens and enhancement of their immunocytochemical expression. The cerebral cortex of non-primate species had an almost exclusive layout of stellate astrocytes, with only the occasional presence of long GFAP-IR processes in the dog that barely crossed the extent of lamina I, which in this species had comparatively increased thickness. Species of Insectivora and Chiroptera showed presence of astrocytes with long processes limited to the ventral basal cortex. Interlaminar GFAP-IR processes were absent in Eulemur fulvus, at variance with their limited presence and large within- and inter-individual variability as reported previously in Microcebus murinus. In New World monkeys such processes were absent in Callithrix samples, at variance with Cebus apella and Saimirí boliviensis. Overall, the expression of GFAP-IR interlaminar processes followed a progressive pattern: bulk of non-primate species (lack of interlaminar processes)--Chiroptera and Insectivora (processes restricted to allocortex) < strepsirhini < haplorhini (platirrhini < catarrhini). This trend is suggestive of the emergence of new evolutionary traits in the organization of the cerebral cortex, namely, the emergence of GFAP-IR long, interlaminar processes in the primate brain. Interlaminar processes may participate in a spatially restricted astroglial role, as compared to the one provided by the astroglial syncytium. It is proposed that the widely accepted concept of an exclusively astroglial syncytium is probably linked with a specific laboratory animal species ("rodent-type" or, rather, "general mammalian-type" model) that misrepresents the astroglial architecture present in the cerebral cortex of most anthropoid adult primates ("primate-type" model), including man.

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

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).

Cortical astroglial conditioned medium induces in vitro radial-like forms.

Cerebral cortex and striatal cell dissociates obtained from rat fetuses (E 17) were subcultured and enriched in astroglial cells before being grown in regional (cerebral cortex, striatum) astroglial conditioned media (CM) or defined basal medium. Incidence of radial-like astroglia (vimentin+ or glial fibrillary acid protein, GFAP+) and length of processes in cortical cell subcultures showed a greater increase when exposed to cerebral cortex CM than to striatal CM or basal medium. Stellate (GFAP+) forms prevailed in subcultures grown in basal medium while striatal cells exposed to CM of either origin remained undifferentiated. Additionally, cultures were treated with various concentrations of cAMP (0.25 and 0.5 mM) and calcitonin gene related peptide (CGRP) (0.1, 0.5, and 1.0 microM). Under these conditions CM-exposed cultures (with predominant "radial-like" forms) did not increase stellate glial numbers, while fetal calf serum (FCS)-exposed cultures (morphologically undifferentiated) underwent significant degrees of stellate transformation. When CM-exposed cultures were shifted to FCS supplemented basal medium for 24-48 hr and then to basal medium alone prior to treatment, cAMP and CGRP were effective in transforming flat astroglia into stellate morphology. Results are indicative of the existence of astroglial diffusible factors affecting the in vitro expression of astroglial morphotypes from the cerebral cortex. Previous exposure to CM interferes with cytoskeletal astrocytic changes induced by cAMP and CGRP. It is speculated that astroglial factors could act in vivo to maintain the expression of radial-like cells during early developmental stages of the cerebral cortex, but it would not be effective in E 17 striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Leptomeningeal and skin fibroblasts: two different cell types?

Leptomeningeal and skin fetal (E16-17) fibroblasts were subcultured in vitro either in DMEM/F12 basal medium (with or without 10% FCS) or in astroglial conditioned medium (ACM). Both populations were characteristically composed of flat, undifferentiated, fibronectin(+), GFAP(-)cells where cultured in fetal serum supplemented basal media. When exposed to ACM leptomeningeal cells developed a population of thin, elongated, fibronectin(+) cells with radial type long processes while skin fibroblasts did not show significant changes in their characteristic morphotype. Exposure to db cAMP in basal medium resulted within 3 hr in their transformation to an astrocytic-like morphotype characterized by a condensed soma and multiple, short processes. Twenty-four hours later skin fibroblasts had returned to their flat appearance while leptomeningeal ones showed elongated, radial-like forms. Results indicate the possible existence of different receptors (to ACM factors) and/or cytoskeletal properties, and suggest that ACM-reactive fibroblasts of leptomeningeal origin represent a different cell type from those of skin origin. The hypothetical role of leptomeningeal cells during brain development is considered.

Trophic influences of human and rat amniotic fluid on neural tube-derived rat fetal cells.

Normal human (week 17-20) and rat (E16-17) amniotic fluids were used as culture media for primary cultures of rat fetal (E 16) cortical, mesencephalic and striatal cell dissociates, or astroglial subcultures from the same brain regions. Phase-bright and dark cells were identified under phase contrast microscopy and their cell processes were measured utilizing semi-automated procedures. Subcultured astroglia were immuno-reacted against glial fibrillary acidic protein and fibronectin. Rat and human amniotic fluid allowed survival and growth of neuronal and non-neuronal cells. Human amniotic fluid samples were trophic in variable degrees. Cerebral cortex subcultured astroglia usually expressed a radial-like morphotype. Although charcoal-adsorbed human amniotic fluid was trophic for primary cultures, its ability to sustain neuritic growth depended on its degree of trophism before treatment. Growth of cell processes in neuronal- and glial-like cells in primary cultures was inhibited to different degrees by the addition of antisera towards nerve or epidermal growth factors. It is concluded that amniotic fluid constitutes a trophic medium for astroglia and neurons. Both, nerve and epidermal growth factors appear to be necessary for growth of cell processes in neuronal and glial primary cultures in amniotic fluid. Trophic effect of amniotic fluid on subcultured astroglia did not seem to be diminished by nerve growth factor antiserum. The role of amniotic fluid during the early phases of brain organogenesis is discussed.