Abstract:
:The accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER) lumen causes a cellular stress response termed the unfolded protein response. Although ER stress has been implicated in various neurodegenerative diseases, the morphological features of aggregated proteins in ER lumina that may cause neurodegeneration have not been well characterized. We examined anterior horn neurons using immunohistochemistry and electron microscopy in 12 sporadic amyotrophic lateral sclerosis (ALS) patients and 12 controls. Approximately 2.6% of both normal-appearing and degenerated motor neurons in ALS cases were immunostained for the ER chaperone protein glucose-regulated protein 78, and approximately 0.1% of these neurons was glucose-regulated protein 78 positive in controls (p = 0.0004). Amyotrophic lateral sclerosis cases also tended to have glucose-regulated protein 78-positive motor neurons more frequently than control cases (p = 0.08). By electron microscopy,neurons in ALS patients showed accumulations of amorphous and granular material suggestive of misfolded or unfolded proteins in dilated predominantly normal-appearing ER. There were also wavy membranous structures extending from the ER membranes that lacked membrane-bound ribosomes, electron-dense material resembling Bunina bodies, Hirano bodies, honeycomb-like structures, and membrane-particle complexes associated with the ER in these neurons. Control sample neurons demonstrated none of these features. These ER alterations suggest that the unfolded protein response is activated in motor neurons in ALS patients and provide the first morphological evidence that ER stress may be involved in the neurodegeneration of motor neurons in early stages of sporadic ALS.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Sasaki Sdoi
10.1097/NEN.0b013e3181d44992subject
Has Abstractpub_date
2010-04-01 00:00:00pages
346-55issue
4eissn
0022-3069issn
1554-6578pii
00005072-201004000-00003journal_volume
69pub_type
杂志文章abstract::Immunofluorescence with laminin antisera revealed a striking change in the localization of this basal membrane glycoprotein in rat sciatic nerve as a result of Wallerian degeneration. The staining was confined to the endoneurium in normal sciatic nerve and during the first days of degeneration. On day 11 endoneurial t...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198401000-00008
更新日期:1984-01-01 00:00:00
abstract::A direct causal relationship between a human DNA virus, adeno serotype 12, and malignant transformation in target cells (sensory retinal neuronal precursors) was suggested by the development of a remarkably uniform retinoblastoma-like neoplasm in rats. In order to focus upon incipient photoreceptor differentiation, 27...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197501000-00003
更新日期:1975-01-01 00:00:00
abstract::A working group supported by the Office of Rare Diseases of the National Institutes of Health formulated neuropathologic criteria for corticobasal degeneration (CBD) that were subsequently validated by an independent group of neuropathologists. The criteria do not require a specific clinical phenotype, since CBD can h...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 指南,杂志文章,实务指引
doi:10.1093/jnen/61.11.935
更新日期:2002-11-01 00:00:00
abstract::Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive traumatic brain injury. Multiple system atrophy (MSA) is a Parkinsonian disorder that can result in repetitive falls with associated head trauma. We hypothesized that patients with neurodegenerative disorders ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlw073
更新日期:2016-10-01 00:00:00
abstract::Lewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement. A fine structural analysis of these two structures has been performe...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198409000-00002
更新日期:1984-09-01 00:00:00
abstract::In adult cerebral astrocytomas, the more anaplasia that is present, the more malignancy that occurs. Cell proliferation antigen staining (MIB-1) and DNA labeling methods for apoptosis using paraffin sections from 39 cases were compared with histopathological grading systems for predicting patient survival. Cases were ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 临床试验,杂志文章
doi:10.1097/00005072-199808000-00004
更新日期:1998-08-01 00:00:00
abstract::This study establishes the sequence of myelination in a population of autopsied infants from birth through the second postnatal year. Myelination was assessed in 62 precisely defined central nervous system (CNS) sites of 162 infants with diverse diseases who were autopsied from 1972 to 1984 at Children's Hospital, Bos...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198705000-00005
更新日期:1987-05-01 00:00:00
abstract::The effects of hypoglycemia on cerebrovascular permeability to a protein, horseradish peroxidase (HRP), were studied in mice given 3 or 8 units of crytalline zinc insulin intraperitoneally. HRP (10 mg in 0.1 ml saline) was injected intravenously 15 to 20 minutes prior to sacrifice. Both mildly and severely hypoglycemi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198005000-00004
更新日期:1980-05-01 00:00:00
abstract::Centrosome amplification is a pivotal mechanism underlying tumorigenesis but its role in gliomas is underinvestigated. The present study specifically examines the expression and distribution of the centrosome-associated cytoskeletal protein gamma-tubulin in 56 primary diffuse astrocytic gliomas (grades II-IV) and in 4...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000229235.20995.6e
更新日期:2006-05-01 00:00:00
abstract::The content of RNA and volume of individual neurons isolated from the nucleus dorsalis and from the ventrolateral portion of the lumbar swelling were determined in eight cases of amyotrophic lateral sclerosis (ALS) and eight controls whose spinal cords were obtained at autopsy. The mean content of RNA in the lumbar mo...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198103000-00009
更新日期:1981-03-01 00:00:00
abstract::The development of deformities during the course of leprosy disease is a major public health concern worldwide. It is possible that cytokine production and apoptosis of Schwann cells (SCs) directly affect nerve degeneration and regeneration leading to injury of the myelin sheath and axon. In the present study, the exp...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000182982.09978.66
更新日期:2005-10-01 00:00:00
abstract::Increasing evidence has demonstrated a vital role of microRNAs (miRNAs) in diverse biological processes. However, their functions in developing brain with hypoxia-ischemia (HI) remain largely unknown. Through a miRNA microarray analysis in a P10 rat model of cerebral HI, we found that miR-30d-5p was one of the most de...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlx052
更新日期:2017-08-01 00:00:00
abstract::To determine whether arterial wall degeneration, in combination with hemodynamic insult, causes cerebral artery aneurysms in a dog model, we simulated the geometry and hemodynamics of a human artery by surgical reconstruction of both common carotid arteries in 12 dogs. The dogs were then randomly assigned to one of th...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000100
更新日期:2014-09-01 00:00:00
abstract::Mutation A30P in the alpha-synuclein gene is a cause of familial Parkinson disease. Transgenic mice expressing wild mouse and mutant human A30P alpha-synuclein, Tg5093 mice (Tg), show a progressive motor disorder characterized by tremor, rigidity, and dystonia, accompanied by accumulation of alpha-synuclein in the som...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/63.4.302
更新日期:2004-04-01 00:00:00
abstract::Despite the key role of γ-aminobutyric acid (GABA) neurons in the modulation of cerebral cortical output, little is known about their development in the human cortex. We analyzed several GABAergic parameters in standardized regions of the cerebral cortex and white matter in a total of 38 human fetuses and infants from...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31822f471c
更新日期:2011-10-01 00:00:00
abstract::Infection with human immunodeficiency virus (HIV) clade C is the most common HIV infection worldwide, yet its impact on the nervous system remains largely unknown. Autopsy studies from regions affected by this virus are scarce, and HIV dementia has only rarely been reported from these countries. Most patients who deve...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181461d3e
更新日期:2007-09-01 00:00:00
abstract::Morphologic investigations of the human visual pathways have been limited by the infeasibility of modern neuroanatomical approaches. Although contemporary methods for tracing axon pathways (such as tracer injections and electrophysiology) have elucidated the visual system in experimental animals, these techniques cann...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::Loss of chromosome 1p/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p/19q deletion based on the high degree of correlation between both parameters in o...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31820c765b
更新日期:2011-03-01 00:00:00
abstract::Natalizumab, a monoclonal antibody directed against α4 integrins, has, to date, been associated with 399 cases of progressive multifocal leukoencephalopathy (PML) worldwide in patients receiving treatment for multiple sclerosis (MS). Because of the limited number of histologic studies, the possible interplay between M...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000005
更新日期:2013-11-01 00:00:00
abstract::The neurodegenerative synucleinopathies, which include Parkinson disease, multiple-system atrophy, and Lewy body disease, are characterized by the presence of abundant neuronal inclusions called Lewy bodies and Lewy neurites. These disorders remain incurable, and a greater understanding of the pathologic processes is ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000262
更新日期:2015-12-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199111000-00004
更新日期:1991-11-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199812000-00009
更新日期:1998-12-01 00:00:00
abstract::Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that are produced by oxidative stress and glutamate transporters (which can contribute to prevention...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.4.350
更新日期:2001-04-01 00:00:00
abstract::In order to induce a non-lethal infection restricted to central aminergic neurons projecting to the olfactory bulbs a series of temperature sensitive (ts) and G-protein monoclonal antibody escape mutants of vesicular stomatitis virus (VSV) were instilled into the nasal cavity of mice. In three-week (wk)-old NMRI mice ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198809000-00001
更新日期:1988-09-01 00:00:00
abstract::A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scal...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198909000-00005
更新日期:1989-09-01 00:00:00
abstract::The content of RNA and the volume of motor neurons isolated from the lateral portion of the cervical swelling were examined in six control and six amyotrophic lateral sclerosis (ALS) cases obtained at autopsy. The mean volume of motor neurons in the ALS group did not differ significantly from the values obtained in th...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::The main hallmarks of human hippocampal sclerosis are neuronal loss and gliosis; reductions in microvasculature labeling in the cornu Ammonis 1 in this condition have been detected using alkaline phosphatase histochemistry. To determine whether the reduction in alkaline phosphatase activity is coupled with a loss of b...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181b08622
更新日期:2009-08-01 00:00:00
abstract::The number and extent of degranulation of mast cells in the sciatic nerve have been determined in Lewis rats inoculated with bovine intradural root myelin to induce experimental allergic neuritis (EAN). No significant change in either the number of mast cells or the percentage of degranulated cells was observed before...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198503000-00008
更新日期:1985-03-01 00:00:00
abstract::Prolonged deprivation of vitamin B12 in rhesus monkeys produced changes in the central nervous system that were indistinguishable topographically and histologically from those of human subacute combined degeneration. Ultrastructural studies of early lesions of the spinal cord disclosed a degeneration of myelin charact...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197805000-00006
更新日期:1978-05-01 00:00:00
abstract::The long-term disabilities associated with spinal cord injury (SCI) are primarily due to the absence of robust neuronal regeneration and functional plasticity. The inability of the axon to regenerate after SCI is contributed by several intrinsic factors that trigger a cascade of molecular growth program and modulates ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa147
更新日期:2021-01-20 00:00:00