Sarah Wurzelmann

Distribution of ectopic neurite growth and other geometrical distortions of CNS neurons in feline GM2 gangliosidosis.

Golgi and combined Golgi-electron microscopic (EM) studies were carried out on cats in the terminal stages of GM2 ganglioside storage disease and the resulting data were compared with those from similar studies of other neuronal storage diseases in cats, including GM1 gangliosidosis. The results support the view that only limited types of neurons affected by the lysosomal hydrolase deficiency and subsequent intracellular storage have the capacity to sprout new dendritic-like growth processes from their axon hillocks, and that these neurons are essentially the same in all of these diseases studied to date. Golgi studies of CNS tissues from GM2 gangliosidosis cats revealed ectopic neurite growth on pyramidal neurons of cerebral cortex and multipolar cells of amygdala and claustrum, whereas other types of neurons responded to the metabolic defect with aspiny meganeurite formation or somatic enlargement, or appeared normal in terms of soma-dendritic morphology. Combined Golgi-EM studies of cortical pyramidal neurons revealed that ectopic, axon hillock neurites commonly possessed asymmetrical synapses which were similar to those observed in other storage disorders.

Microtubule disarray in cortical dendrites and neurobehavioral failure. I. Golgi and electron microscopic studies

Cortical biopsies obtained from 5 young children with severe neurobehavioral retardation of unknown etiology have been analyzed using Golgi and EM techniques. The normally cylindrical geometry of individual dendritic processes of pyramidal and non-pyramidal neurons is interrupted by the formation of distinct varicosities. While over 90% of observed cells are affected, the extent of varicosity formation varies from cell to cell and is most prominent in medium and small pyramidal cells. Varicosities may occur in the periphery only, or they may extend proximally to primary dendritic trunks. Accompanying changes include thin and irregular proximal processes, loss of dendritic spines, and predominance of long, thin tortuous spines. Ultrastructural analysis reveals characteristic changes in the cytoskeleton of these processes. Microtubules, within the larger proximal processes, twist and turn, relative to one another and relative to the long axis of the process. In varicose regions, microtubules course in roughly parallel array through constricted segments, only to splay away from one another on entering an expansion. Synapses are evident on constricted and expanded segments, as well as on spines. Alterations in dendritic structure of both pyramidal and non-pyramidal neurons may represent a primary target in the pathobiological process underlying neurobehavioral failure.

Ultrastructural study on nuclear-cytoplasmic relationships in oocytes of the African lungfish, Protopterus aethiopicus

SummaryFor a limited period during the oogenesis of Protopterus, blebs of the perinuclear cistern contain, in addition to other inclusions, a special kind of microtubular elements. Most of these blebs face parts of multiple nucleolar bodies that extend toward and make contact with the inner nuclear membrane. The microtubular lumen contains a finely dispersed material of moderate electron density which seems to be in contact with this nucleolar material.Aside from these intracisternal structures there are, within both the perinuclear cytoplasm and the nucleoplasm, similar microtubular arrays without apparent connection with the nuclear envelope. These are either enclosed by membranes derived from those of the envelope or unconfined, having escaped through breaks in their respective bounding membranes. Extracisternal tubules are presumed to have passed their period of putative functional activity and to be undergoing a process of regression and subsequent disintegration.Among possible roles attributable to the intracisternal microtubular apparatus are the following: (1) It may serve for the transport of special nucleolar components to the cytoplasm, possibly to be incorporated in the matrix of developing perinuclear mitochondria; (2) it may provide openings in the nuclear membranes for the direct passage of particulate elements between nucleus and cytoplasm; (3) it may be instrumental in the breakdown of parts of the nuclear envelope prior to its restitution during the subsequent phase of oogenesis.

Neurosecretion. XVII. Experimentally induced release of neurosecretory material by exocytosis in the insect Leucophaea maderae.

SummaryIn the corpora cardiaca of the insect Leucophaea the administration of serotonin elicits ultrastructural features indicative of the extrusion of neurosecretory material by exocytosis. The response to the stimulus and the process of extrusion seem to occur at considerable speed. Nearly all of the 30 test animals, fixed at various intervals starting as early as 3 min after the injection of the drug, show granules captured at the moment of leaving the axon as well as fully exteriorized secretory material. The fact that many of these granules are much smaller than the typical neurosecretory type speaks for intracellular fragmentation of the latter prior to the discharge of this cellular product. After 25 min or more the extruded electron dense structures show signs of breakdown. The apparent speed of these phenomena accounts for the dearth of omega-type configurations observed in unstimulated specimens of this species. The possible relationship between the membrane phenomena involved in exocytosis and the transient protrusions of bounding membranes of neurosecretory granules described in earlier papers remains to be clarified.

Ectopic axon hillock-associated neurite growth is maintained in metabolically reversed swainsonine-induced neuronal storage disease *

An experimentally induced and reversible model of a neuronal storage disease, swainsonine-induced feline alpha-mannosidosis, has been used to study the modifiability of ectopic, axon hillock-associated neurites and their new synaptic contacts. Earlier studies have fully documented that a variety of neuronal storage disorders are characterized by such changes in neuronal geometry and connectivity. Swainsonine administration was ended after 6 months of continuous treatment which had resulted in characteristic signs of alpha-mannosidosis. Studies of this animal 6 months after reversal showed that even though neuronal vacuolation and other CNS changes essentially normalized, ectopic neurites and their synaptic connections were still present and appeared similar to those of another animal which had been treated with swainsonine for the entire 12-month period. These results suggest that once initiated during the disease process, ectopic axon hillock-associated dendrites become an integral part of the soma-dendritic domain of affected neurons and may not be reversible. These findings may have relevance for current attempts to devise therapies involving enzyme replacement for individuals with inherited neuronal storage disease.

Survey for mitochondrial-desmosome complexes in differentiating epithelia

SummaryMitochondria are frequently found to be closely associated with the plaques of desmosomes in a variety of columnar or cuboidal epithelia of fetal or early postnatal mammals (mouse, rat, human being). The organs in which mitochondrial-desmosome complexes were found include stomach, small intestine, pancreas, kidney, epididymis, seminal vesicle, coagulating gland, thyroid gland. The association has not been observed in simple squamous epithelium (vascular endothelium). Mitochondria lie quite close to desmosomes in the stratum spinosum of stratified squamous mucous epithelium of fetal animals and also to axo-dendritic synapses in still poorly differentiated central nervous system. Mitochondria have also been detected close to attachment sites in ectoderm of the early frog gastrulae. Here there is as yet no visible plaque material.We suggest that the mitochondria may provide energy or some chemical for the formation of the plaque. This hypothesis does not explain why the complexes are not found in poorly differentiated epithelia from older animals.

Vestibular axons form synapses on abnormally derived Mauthner cells

Abstract Axolotl prospective forebrain-midbrain can be reprogrammed to differentiate as Mauthner cell (M-cell)-containing medulla 12 . Light and electron microscopic examination of the abnormally derived M-cells reveals vestibular club endings appropriately localized on the ventral surface of their lateral dendrites. This observation indicates that the surface of such cells is like that of ordinary M-cells insofar as it is recognized and forms synapses with vestibular axons.