Transplantation of human cortex with Alzheimer's disease into rat occipital cortex; a model for the study of Alzheimer disease

Summary Senile dementia of the Alzheimer type (SDAT) is a major problem in the human senescent population. As this pathology cannot be reproduced in animals, research into its development is greatly impeded. The technique of implantation of the nervous tissue has been utilized in order to establish an animal model and to test the possible existence of a transmissible agent. When human temporal cortex with Alzheimer's disease is implanted in the occipital cortex of 7-week-old rats, human cerebral tissue containing abundant tangles induces in the receiver cortex a reactive fibrous gliosis. In the processes of the astrocytes, twisted filaments are evident among bundles of normal filaments. These alterations could be induced by the metabolising of abnormal filament subunits or by some infectious agent introduced by the implant.This study is supported by grant No. 2.4517.82 of Fonds de la Recherche Fondamentale Collective of Belgium.     

Dense core vesicles in cerebral cortex of the human fetus.

The present study clearly demonstrates that by the 15th week of gestation dense core vesicles appear within the human cerebral cortex. These vesicles can be identified within axon cylinders, axon growth cones, and axon synaptic terminals. The role of these vesicles is speculative, yet, their very presence at this early fetal stage seems to reflect an advanced state of synaptic vesicle development.     

Arteriovenous anastomoses in the juxtamedullary cortex of human kidney

Summary In the juxtamedullary cortex of normal human kidney the existence of arteriovenous anastomotic channels is demonstrated by means of microscopic observation. A clear arteriovenous anastomosis occurring at the level of an afferent arteriole is also presented.     

Demonstration of high affinity binding of estradiol in adrenal cortex tissue]

Evidence is presented demonstrating the presence of a high affinity (Ka10(8)M-1), limited capacity (3-4 pmoles/mg protein) estradiol binder in the soluble fraction of the Bovine, Rat and Human adrenal cortex. The binding appears specific to the estrogen structure whereas C19 and C21 steroids do not bind. Upon sucrose density gradient centrifugation, the estradiol binder sedimented at 9 S at low ionic strength and was shifted to 4.5 S in the presence of 0.5 M KCl. This demonstration of a receptor-like moiety for estradiol in the adrenal cortex lends biochemical support to previous observations suggesting that adrenal cortex functions may be modulated by a direct effect of gonadal steroid hormones.     

Structure and function of desmosomal proteins and their role in development and disease

Desmosomes represent major intercellular adhesive junctions at basolateral membranes of epithelial cells and in other tissues. They mediate direct cell-cell contacts and provide anchorage sites for intermediate filaments important for the maintenance of tissue architecture. There is increasing evidence now that desmosomes in addition to a simple structural function have new roles in tissue morphogenesis and differentiation. Transmembrane glycoproteins of the cadherin superfamily of Ca²⁺-dependent cell-cell adhesion molecules which mediate direct intercellular interactions in desmosomes appear to be of central importance in this respect. The complex network of proteins forming the desmosomal plaque associated with the cytoplasmic domain of the desmosomal cadherins, however, is also involved in junction assembly and regulation of adhesive strength. This re-view summarizes the structural features of these desmosomal proteins, their function during desmosome assembly and maintenance, and their role in development and disease.Received 5 February 2003; received after revision 14 March 2003; accepted 1 April 2003     

Absence of lipolytic action of adrenaline on a human subcutaneous adipose tissue. Role of alpha-adrenergic receptors]

Epinephrine cannot stimulate adipocytes' lipolysis of human subcutaneous adipose tissue (lateral part of the thigh) while a clear lipolytic action can be shown on the omental tissue. However, at the same concentrations, isoproterenol (a beta-agonist) exerts a strong adipokinetic effect on adipocytes of the both types of adipose tissue. An alpha-adrenolytic (phentolamine) enhances the lipolytic action of epinephrine on the omental adipose tissue and unmasks a lipolytic action of epinephrine on the subcutaneous. Epinephrine antagonizes the lipolysis induced by theophyline on the subscutaneous adipocytes, this action is increased by propranolol (a beta-adrenergic blocking agent). The unresponsiveness to epinephrine of the subcutaneous adipose tissue studied here could be linked to a strong antilipolytic alpha-adrenergic effect.     

A simple method for observation of capillary nets in rat brain cortex

Summary By the authors' technic, the profiles of capillaries in rat brain cortex were clearly demonstrated. The capillaries formed complicated nets by sprouting of their finer branches and anastomosing with each other. Further, a kind of perivascular cells with yellow autofluorescent granules was distributed close to capillaries, arterioles or venules. They seemed to be a special form of macrophage in the brain cortex.     

A simple method for observation of capillary nets in rat brain cortex.

By the authors' technic, the profiles of capillaries in rat brain cortex were clearly demonstrated. The capillaries formed complicated nets by sprouting of their finer branches and anastomosing with each other. Further, a kind of perivascular cells with yellow autofluorescent granules was distributed close to capillaries, arterioles or venules. The seemed to be a special form of macrophage in the brain cortex.     

The specification of neuronal identity in the mammalian cerebral cortex

The determination of neuronal fate in the developing cerebral cortex has been studied by tracking normal cell lineages in the cortex, and by testing the commitment of young cortical neurons to their normal fates. These studies together suggest that neuronal progenitors are multipotent during development and have the potential to produce neurons destined for many or all of the cortical layers. However, the laminar identity of an individual neuron appears to be specified through environmental interactions at the time of the cell's terminal mitotic division, prior to its migration into the cortical plate.     

The specification of neuronal identity in the mammalian cerebral cortex

Summary The determination of neuronal fate in the developing cerebral cortex has been studied by tracking normal cell lineages in the cortex, and by testing the commitment of young cortical neurons to their normal fates. These studies together suggest that neuronal progenitors are multipotent during development and have the potential to produce neurons destined for many or all of the cortical layers. However, the laminar identity of an individual neuron appears to be specified through environmental interactions at the time of the cell's temrinal mitotic division, prior to its migration into the cortical plate.     

Alexander disease: putative mechanisms of an astrocytic encephalopathy

Alexander disease (AXD) is the first primary astrocytic disorder. This encephalopathy is caused by dominant mutations in the glial fibrillary acidic protein (GFAP) gene, encoding the main intermediate filament of astrocyte. Pathologically, this neurodegenerative disease is characterised by dystrophic astrocytes containing intermediate filament aggregates associated with myelin abnormalities.More than 20 GFAP mutations have been reported. Many of them cluster in highly conserved regions between several intermediate filaments. Contrary to other intermediate filament-related diseases, AXD seems to be the consequence of a toxic gain of function induced by aggregates. This is supported by the phenotype of mice overexpressing human GFAP. Nevertheless, GFAP null mice display myelin abnormalities and blood-brain barrier dysfunction that are present in AXD.Given the pivotal role of astrocytes in brain physiology, there are many possibilities for astrocytes to dysfunction and to impair the functions of other cells. Physiopathological hypotheses are discussed in the frame of AXD.Received 11 April 2003; received after revision 22 July 2003; accepted 31 July 2003Both authors contributed equally to this work.     

Cell lineage and cell migration in the developing cerebral cortex

Summary Modern techniques which trace lineages of individual progenitor cells have provided some clues about the processes that determine cell fate in the brain, and have also given us some information about migratory patterns of clonally related cells. In many parts of the central nervous system, progenitors are multipotent; single clones can contain multiple neuronal types or even mixtures of neurons and glia. In addition, one can observe a wide distribution in clone size, even when marking is done in a narrow time window. This suggests that progenitor cells may be fairly plastic and responsive to environmental signals. In the developing cortex, clonally related cells are initially grouped near each other, as in the retina and tectum. However, the subsequent migration of these cells from the ventricular zone to the cortex along glial fibers is accompanied by a progressive dispersion of clonally related neurons.     

Focal brain hyperthermia. I. The cerebellar cortex

Focal brain hyperthermic methodology has been described and data presented on the cerebellum which show that enhancement of electrical activity of cerebellar cortex occurs when this method is used with careful monitoring of temperature. The duration of electrically induced cerebral after-discharges is shortened when cerebellar warming reaches 39.5--42.0 degrees C,. Since these effects are repeatable over many hours, there appears to be little, if any, resultant damage. Such induced changes in the cerebrum resemble those previously reported in which electrical stimuli were applied to the cerebellar cortex.     

Focal brain hyperthemia. I. The cerebellar cortex

Summary Focal brain hyperthemic methodology has been described and data presented on the cerebellum which show that enhancement of electrical activity of cerebellar cortex occurs when this method is used with careful monitoring of temperature. The duration of electrically induced cerebral after-discharges is shortened when cerebellar warming reaches 39.5–42.0°C. Since these effects are repeatable over many hours, there appears to be little, if any, resultant damage. Such induced changes in the cerebrum resemble those previously reported in which electrical stimuli were applied to the cerebellar cortex.We sincerely thank the United States Public Health Service for financial support from grant No. NS11929.     

Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin

Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them inaccessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to F-actin, resulting in actin depolymerization. Cells overexpressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells.     

Human embryonic stem cell-derived neurons establish region-specific, long-range projections in the adult brain

While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved. We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro, lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain.     

Free amino acids in motor cortex of amyotrophic lateral sclerosis.

Free amino acids were estimated quantitatively in the motor cortex from 3 patients with amyotrophic lateral sclerosis (ALS) and 11 control subjects. Among 7 amino acids which showed statistically significant changes, taurine was the only one which was increased constantly and most markedly in the motor cortex of all the 3 ALS cases. It was suggested that the metabolism of sulfur amino acids might be affected in comparatively early stages of ALS.     

Influence of the visual cortex upon collicular evoked responses in the rabbit.

In rabbit, the depression of the visual cortex by KCl showed an enhancement of the collicular evoked potentials. This enhancement revealed that the visual cortex had exerted a tonic type influence upon the superior colliculus.     

Free amino acids in motor cortex of amyotrophic lateral sclerosis

Summary Free amino acids were estimated quantitatively in the motor cortex from 3 patients with amyotrophic lateral sclerosis (ALS) and 11 control subjects. Among 7 amino acids which showed statistically significant changes, taurine was the only one which was increased constantly and most markedly in the motor cortex of all the 3 ALS cases. It was suggested that the metabolism of sulfur amino acids might be affected in comparatively early stages of ALS.Acknowledgments. The authors are grateful to Dr M. Uono, Department of Neurology, Tokyo Metropolitan Hospital of Fuchu, and Dr K. Hirayama, Department of Neurology, Brain Research Institute, School of Medicine, Chiba University, for their generous cooperation.