Honeycomb-like intra-axonal tubular structures in irradiated rat cerebella

Summary In the cerebella of all (5) 30-days old rats, whose cerebellar region was irradiated with 1000 r at the 2nd day of life, honeycomblike tubular arrays were found in myelinated axons, identical with those described by others in a variety of conditions.

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Zusammenfassung Im Kleinhirn aller (5) 30 Tage alter Ratten, deren Kleinhirnregion mit 1000r am Ende des 2. Lebenstages bestrahlt worden war, fanden sich honigwabenartige tubuläre Formationen in den bemarkten Axonen, die den von anderen Autoren bei verschiedenen Bedingungen beschriebenen Veränderungen entsprechen.

     

Ultrastructural pathology of dermal axons and Schwann cells in lysosomal diseases

Summary Skin tissue specimens, obtained from 60 patients afflicted with a diverse range of lysosomal disorders revealed two groups of lesions within dermal axons, largely unmyelinated ones, particularly within axonal terminals: (1) non-specific mitochondria and dense bodies often enlarging the axonal terminal; and (2) disease-specific lysosomal residual bodies, the latter less frequent depending on the incidence and type of lysosomal disorders, i.e., largely only seen in GM₂-gangliosidosis due to hexosaminidase A deficiency and mucolipidosis IV, while the spectrum of lysosomal residual bodies in Schwann cells appeared more variegated, especially due to the occurrence of vacuolar lysosomal residual bodies which were never seen within axons. The most frequent location of abnormal intraaxonal constituents in terminal axons indicates a functionally and morphologically impaired retrograde axonal transport but provides no further evidence as to whether the respective parent nerve cell body has also accumulated lysosomal residual bodies. When studying biopsied skin specimens for diagnosis, axonal terminals beneath the epidermis, about sweat glands, and among smooth muscle cells, ought to be incorporated into a comprehensive electron microscopic examination.This paper was, in part, presented at the Annual Meeting of the Deutsche Gesellschaft für neuropathologie und Neuroanatomie, Mainz, October 1986, and represents part of a medical thesis by S. Walter to be submitted to the Fachbereich Medizin der Johannes-Gutenberg-Universität Mainz     

Dysmyelination in Chow Chow dogs: Further studies in older dogs

Summary The ultrastructure of myelin deficiency in Chow Chow dogs was studied in the spinal cord of a 15-month-old and a 3-year-old animal. It was found that myelination progresses with age in these dogs but is still deficient at the age of 3 years. The findings included axons with thin or uncompacted myelin sheaths, separated from each other by massive astrocytosis, and bizarre myelin formations. Normal numbers of morphologically normal oligodendrocytes were present in the myelin-deficient areas. The disease in these Chow Chow dogs consists of a strongly retarded myelination which is possibly due to a dysfunction or delay in glial maturation.Supported by the Schweizer Nationalfonds grant no. 3.805.79     

Dysmyelination of the central nervous system in the Chow-Chow dog

Summary Five Chow-Chow dogs from three different litters had generalized body tremors since birth. Histologically a severe myelin deficiency was found in the central nervous system. The peripheral nerves were normally myelinated. Electron microscopically abnormally thin myelin sheaths and completely naked nerve fibers were found. There were many astrocytes in the myelin deficient areas as well as cells with the characteristic features of oligodendrocytes but also containing fibrils. The present cases are compared to other dysmyelinating diseases and possible pathogenetic mechanisms are discussed.Publication No 1300 School of Vet. Medicine Auburn University     

Spheroids and altered axons in the spinal gray matter of the normal cat

Summary In our recent ultrastructural studies on synapses of the nucleus dorsalis, central cervical nucleus, and anterior horn of the spinal cord of the normal cat we happened to find spheroids and several types of axonal alterations. These spheroids were up to 39 m in diameter. They were found in myelinated and unmyelinated terminal axons and at the node of Ranvier and showed two different types of internal structure. One type was large and composed of spirally arranged neurofilaments and mitochondria in increased quantity, although the mean population density of mitochondria was not high being 1.4/m² as compared to the normal value 2.0/m². Another type was smaller and consisted of small mitochondria and dense bodies which were increased in number: their mean population densities were 4.5/m² and 1.9/m², respectively.At present, the rare occurrence of spheroids and atypical axonal alterations makes it difficult to determine the origin of affected axons, although some of them presumably arise from primary afferents.     

The central nervous system in canine giant axonal neuropathy

Summary The pathology of the central nervous system (CNS) in a dog with giant axonal neuropathy (GAN) is presented. Swollen axons containing excessive and disorganised neurofilaments were present in the spinal cord, mainly at the distal portions of long tracts. The fasciculus gracilis and dorsal spinocerebellar tracts were affected only in the rostral cervical cord while the lateral cortico spinal tract was principally involved in the lower thoracic and lumbar cord. Occasional swellings were also found in the central dorsal columns of the rostral lumbar segments and in the dorsal and intermediate grey matter. The nuclei gracilis and cuneatus, restiform body and ventral spinocerebellar tracts were all involved in the brain stem. Spheroids were seen in the white matter of the rostral cerebellar vermis and in the granule cell layer. The brachium of the superior colliculus contained swollen axons and the cortex was diffusely involved with spheroids. The distribution was of a distal axonopathy and the cortical changes provided an explanation for the abnormal EEG and mental retardation found in some human patients.     

Ultrastructural evidence of a peripheral nervous system pattern of myelination in the avascular retina of the guinea pig

Summary Myelination of axons in the nerve fiber layer (NFL) of the retina occurs as a sporadic abnormality in several mammalian species including man, monkey, cat and rat. All of these species have vascularized retinae and, in the latter three, ultrastructural studies have demonstrated the pattern of medullation to be similar to Schwann cell myelination in the peripheral nervous system. This contrasts with an oligodendrocytic pattern of myelination normally present in the avascular retina of the rabbit. One possible explanation for this difference is that the pattern of myelination is related to the presence or absence of retinal blood vessels. The present investigation provides the first evidence of NFL myelination in another avascular retina, that of the guinea pig. Myelination in the guinea pig retina was observed in a single bundle of axons and involved only large diameter fibers. With several axons, myelin sheaths terminated at hemi-nodes of Ranvier and in all such cases this occurred in association with marked paranodal infolding. Morphological characteristics of the myelination include (1) a one to one relationship between axon and myelinating cell, (2) cytoplasm between myelin sheath and plasma membrane, (3) basal lamina surrounding the myelinating cell, (4) collagen fibers in the adjacent extracellular space and (5) double intraperiod lines. These morphological features are characteristic of peripheral nerve myelination by Schwann cells. Thus, in all species so far described in which retinal medullation is abnormally present, the pattern of myelination has been Schwann cell in nature rather than oligodendrocytic. The reasons for this Schwann cell predominance remain undefined.Supported by the Medical Research Council of Canada     

Tubular aggregates in skeletal muscle of chronic alcoholic patients

Summary The presence of tubular aggregates (TA) in type II muscle fibers in two of 20 alcoholic patients with chronic liver disease, and with no apparent neuromuscular disorder, is reported. The localization, histochemical reactions, and ultrastructural features of the TA are similar to those previously described in other conditions. In one of the two cases TA were demonstrated by E/M observations only and not by histochemistry.No correlations were found between the biochemical changes and the presence of tubular aggregates.We believe that TA are long-standing structures since the muscle biopsies were performed 12 and 13 days after the ingestion of alcohol had been discontinued. They may represent a non-specific response of the sarcoplasmic reticulum to compensate for the deficient calcium uptake reported in alcoholic patients.     

Spongiform-like changes in Alzheimer's disease

Summary The ultrastructural study of the cortex of four patients with sporadic or familial AD, of two agematched controls without dementia, and of one normal pressure hydrocephalus, revealed in all the cases in the neuropil only occasional vacuoles which had a morphology similar to those observed in CJD. The degree of spongiform-like changes was, however, far less prominent than in CJD and considered mild in all the cases examined. Moreover, curled fragments of membranes within the vacuoles were not observed. It is suggested that the mild vacuolization of the neuropil occasionally observed in cortical biopsies of AD is a non-specific finding and cannot be considered a neuropathologic link between AD and CJD.     

Appearance of tubulovesicular structures in experimental Creutzfeldt-Jakob disease and scrapie preceeds the onset of clinical disease

Summary We have consistently observed tubulovesicular structures in brain tissues during the terminal stages of naturally occurring and experimentally induced spongiform encephalopathies, irrespective of the host species and virus strain. In NIH Swiss mice inoculated intracerebrally or intraocularly with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus, tubulovesicular structures, measuring 20–50 nm in diameter, were particularly prominent in dilated, pre-and postsynaptic neuronal processes, occasionally being mixed with synaptic vesicles. These structures appeared 13 weeks following intracerebral inoculation, 5 weeks before the onset of clinical signs, when spongiform changes were also detected. The number and density of tubulovesicular structures increased steadily during the course of clinical disease, and were particularly abundant in mice 47 to 51 weeks after intraocular inoculation. In hamsters infected with the 263 K strain of scrapie virus, these structures were initially detected 3 weeks following intracerebral inoculation and increased dramatically at 10 weeks postinoculation. The appearance of tubulovesicular structures before the onset of overt disease in mice inoculated with CJD virus by either the intracerebral or intraocular route, and before the appearance of other neuropathological changes in hamsters infected with scrapie virus, indicate that they represent either a part or aggregate of the infectious virus or a pathological product of the infection.Presented in part at the 64th annual meeting of the American Association of Neuropathologists, held in Charleston, South Carolina, June 9–12, 1988 and at the 7th annual meeting of the American Society for Virology, Austin, Texas, June 12–16, 1988. Dr. Pawel P. Liberski is a recipient of a fellowship from the Fogarty International Center and a grant from the Ministry of Health and Social Welfare, Poland     

Pituitary growth hormone cell adenoma with cytoplasmic tubular aggregates in the capillary endothelium

Summary Electron microscopy revealed the presence of cytoplasmic tubular aggregates in the capillary endothelium of a sparsely granulated growth hormone cell adenoma removed surgically from a 25-year-old female patient with acromegaly. To our knowledge, this is the second publication describing these structures in hypophysial growth hormone cell adenomas.     

The fine structure of plaques fibromyéliniques in ulegyria and in status marmoratus

Summary A 12 year old boy with a history of perinatal injury resulting in encephaloclastic porencephaly is described. Electron microscopic examination of the plaques fibromyéliniques in areas of ulegyria and status marmoratus revealed that they mainly consist of fibrillated processes, apparently of astrocytic origin, surrounded by myelin lamellae. Hypermyelinization of some of these processes was also present. These observations suggest excessive regenerative activity on the part of myelin-forming glial cells.This work was supported by Neuropathology Training Grant 5T01-NB-05500-3 and Research Grant NB A1 07380-01A1 from the National Institute of Neurological Diseases and Stroke, U. S. Public Health Service, Bethesda, Maryland.     

Peripheral nerve changes in porphyric neuropathy: Findings in a sural nerve biopsy

Summary The changes in a sural nerve biopsy of a patient with porphyric neuropathy were studied by light and electron microscopy. Linear arrays of myelin ovoids constituted the most common abnormality in whole mounts of teased-fiber preparations. Round or irregular formations of variable osmiophilia were the most frequent finding in thick-section preparations examined by phase contrast microscopy. Lamellar whorls represented the most prevalent lesion in thinsections studied under the electron microscope. In addition, along the teased fibers, segmental demyelination was definitely detected, although rarely; in thick sections, the true extent of the nerve fiber loss was fully appreciated; in thin sections, a variety of axon and myelin changes of a distinct character were discovered. The studies demonstrate that in peripheral nerves of porphyric neuropathy, axonand myelin changes generally run together and proceed pari passu in the same segment of nerve fiber. Furthermore, among the pathogenetic mechanisms invoked to account for the neuropathic changes none are favored to the exclusion of others by these studies. Therefore, a primary axonaland myelinic disorder on the basis of a deranged porphyrin metabolism is as good a possibility as any hitherto advanced explanation of the pathogenesis of the neuropathic changes. The secondary lesions of Wallerian degeneration and segmental demylination may simple be grafted upon the primary lesions evoked by the metabolic abnormality.     

Serotonin axon terminals in the ventral tegmental area of the rat: fine structure and synaptic input to dopaminergic neurons

The serotoninergic (5-hydroxytryptamine, 5-HT) innervation of the rat ventral tegmental area (VTA) was examined by light and electron microscopic radioautography following intraventricular infusion of [³H]5-HT. The [³H]5-HT labeled processes were characterized with respect to their regional distribution, ultrastructure and relationships with all neurons, including dopaminergic neurons, identified in the same sections using immunocytochemistry for the localization of the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). By light microscopy, [³H]5-HT labeled axons and axonal varicosities were detected throughout the interfascicular nucleus and ventral portion of the VTA. By electron microscopy, [³H]5-HT-labeled axons were found to be mainly small and unmyelinated, although a few showed several lamellae of myelin. The labeled varicosities measured 0.6 μm in mean diameter and contained many small, round or flattened agranular vesicles and a few large granular vesicles. More than 18% showed synaptic specializations in single thin sections. Most of these synapses were asymmetric and established on dendritic shafts. Based on the probability of seeing such synaptic specializations in single thin sections, it was estimated that as many as 50% of the labeled 5-HT terminals formed synaptic contacts in the VTA. In dually labeled light microscopic sections, [³H]5-HT-accumulating processes often appeared adjacent to TH-immunoreactive perikarya and proximal dendrites. Electron microscopy demonstrated that terminals with radioautographic labeling for 5-HT formed conventional synapses both with TH-labeled and unlabeled dendrites in the VTA. Many additional 5-HT terminals lacking recognizable synaptic densities were directly apposed to TH-labeled dendrites and were isolated from the rest of the neuropil by thin glial leaflets. These results suggest that 5-HT neurons innervate both dopaminergic and non-dopaminergic neurons in the VTA and may influence mesocortical and mesolimbic efferent systems through synaptic as well as non-synaptic mechanisms.     

The fine structure of subcortical neurofibrillary tangles in progressive supranuclear palsy

Summary The fine structure of subcortical neurofibrillary tangles was investigated in pallidum, substantia nigra, periaqueductal gray, pontine reticular gray, and dentate nucleus of 5 autopsy cases of Progressive Supranuclear Palsy. Only tangles due to straight 150 Å wide filaments have been detected. These findings, obtained from a large series of cases and areas examined, confirm previous observations on the fine structure of neurofibrillary tangles in Progressive Supranuclear Palsy and suggest that the association between tangles due to straight filaments and tangles due to twisted tubules, so far described in one case, is probably exceptional.This investigation was financially supported by the Ministero per la Pubblica Istruzione and Regione Liguria     

Electron microscopic structure of the alzheimer's neurofibrillary changes in case of atypical senile dementia

Summary A man aged 70, showed early disorientation, memory defects, delusions and rages at 66, later mental deterioration with muteness and dysphagia. He died of cardiac failure. The postmortem examination revealed macroscopically and light microscopically the neuropathological findings of atypical senile dementia.Moreover, it is the interesting characteristic in the presented case that there are electron microscopically two types of filaments making the neurofibrillary tangles. One showed the so-called paired helical filaments, which were observed in the cerebral cortex. The other showed parallel straight filaments. These straight filaments were found in the bilateral hippocampi.     

Electron microscopic studies on the cerebral lesions of rats in experimental chronic disulfiram poisoning

Summary Following chronic administration of disulfiram to rats, changes of the brain were examined electron-microscopically. Pathological findings were observed in the nerve cells of the cerebral cortex and hypothalamus at later stage, and synaptic changes in the hypothalamus from initial stage. On the other hand, changes of myelinated fibers, neuroglias and capillaries were very slight. It was considered that neurons were affected more predominantly than other neuronal elements by the cytotoxic action of the drug, and that the synaptic changes of the hypothalamus might reveal chronic disturbance of noradrenergic transmission by inhibition of dopamine--hydroxylase. These ultrastructural findings might relate to the pathogenic mechanism of the disulfiram psychosis.