Abstract:
:There is increasing evidence that oxidative damage plays a major role in amyotrophic lateral sclerosis (ALS), but how it contributes to motor neuron degeneration and astrocytic gliosis, two pathologic hallmarks of the disease, is unknown. A few studies have suggested that ALS motor neurons die via apoptosis and show upregulation of c-jun, an immediate early gene that is necessary for neuronal apoptosis. In order to elucidate the mechanisms of cell damage induced by oxidant stress, we have studied in ALS and control spinal cord the immunohistochemical expression of c-Jun, of JNK/SAPK, a kinase that activates c-Jun following various types of stress, and of NF-kappa B, a transcription factor that is induced by oxidant stress and has prominent neuroprotective functions. An in situ end-labeling assay was performed for detecting apoptotic cells. We show that (a) the JNK/SAPK-c-Jun pathway is dramatically overexpressed in ALS spinal cord; (b) the strongest activation occurs in astrocytes, while motor neurons show unusually low expression of the pathway; (c) increased JNK/SAPK expression in glial cells is accompanied by NF-kappa B activation, indicating the presence of a protective response to oxidant sress, which is deficient in motor neurons; (d) activation of JNK/SAPK, c-Jun and NF-kappa B is unrelated to apoptotic cell death. These results support the view that astrocytes are directly involved in the pathologic process of ALS, and might explain the selective vulnerability of motor neurons by their relative lack of antioxidant defenses.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Migheli A,Piva R,Atzori C,Troost D,Schiffer Ddoi
10.1097/00005072-199712000-00006subject
Has Abstractpub_date
1997-12-01 00:00:00pages
1314-22issue
12eissn
0022-3069issn
1554-6578journal_volume
56pub_type
杂志文章abstract::We performed a prospective, longitudinal immunohistochemical study of the spinal cords of transgenic mice with a G93A mutant SOD1 gene at 4 fixed points in time, using antibodies to inducible nitric oxide synthase (iNOS) and nitrotyrosine. The purpose of this study was to characterize the temporal and topographic dist...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1093/jnen/60.9.839
更新日期:2001-09-01 00:00:00
abstract::Cysteine-S-sulfate is an abnormal metabolite discovered in the urine and blood of a patient with cysteine oxidase deficiency, a rare disorder of sulfur amino acid metabolism associated with brain damage and mental retardation. The molecular structure of cysteine-S-sulfate closely resembles that of glutamate and relate...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-197503000-00005
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abstract::Neuropathologists use anti-glial fibrillary acidic protein (GFAP) antibodies as specific markers for glial cells, and neurobiologists use GFAP for targeting transgenes to glial cells. Since GFAP has also been detected in non-glial cells, we systematically analyzed GFAP expression in human and murine non-CNS tissues us...
journal_title:Journal of neuropathology and experimental neurology
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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
abstract::In many degenerative and metabolic muscle diseases cells die without a marked inflammatory response. A potential mechanism how this could be accomplished is apoptotic cell death. Since there are no data available about apoptosis in cells of myogenic origin, we examined rat skeletal myoblasts for their potential to und...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199601000-00004
更新日期:1996-01-01 00:00:00
abstract::Genome-wide association studies have established BIN1 (Bridging Integrator 1) as the most significant late-onset Alzheimer disease (AD) susceptibility locus after APOE We analyzed BIN1 protein expression using automated immunohistochemistry on the hippocampal CA1 region in 19 patients with either no, mild, or moderate...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1093/jnen/nlw056
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abstract::McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings to those in McArdle dise...
journal_title:Journal of neuropathology and experimental neurology
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abstract::A superoxide dismutase 1 (SOD-1)genetic defect has been identified in familial amyotrophic lateral sclerosis (ALS) and motor neuron degeneration has been described in SOD-1 transgenic mice. Because an excitotoxic mechanism has been implicated in ALS, we undertook studies to provide a description of excitotoxic degener...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199602000-00010
更新日期:1996-02-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-199812000-00009
更新日期:1998-12-01 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::Brainstem Lewy bodies (LB) are neuronal inclusions that are closely related to Parkinson's disease (PD). The filamentous component of LB from patients with PD contains biochemically altered neurofilaments (NF). Herein we have tested the hypothesis that the oxidized products of catechols may covalently crosslink NF. Ne...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199505000-00004
更新日期:1995-05-01 00:00:00
abstract::Increased numbers of corpora amylacea have been observed in the resected mesial temporal lobe of many patients with complex partial seizures (CPS) and Ammon's horn sclerosis (AHS). Several heat shock proteins (HSPs) are induced by seizures and have been suggested as an etiologic factor in the formation corpora amylace...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1093/jnen/59.8.698
更新日期:2000-08-01 00:00:00
abstract::Shigella dysenteriae strains produce an exotoxin (SdT) which inhibits protein synthesis in susceptible cells and is neurotoxic in some species. Intraneural microinjection of highly purified SdT into the cervical vagus nerves of rats, mice, guinea pigs and rabbits produced cytopathic changes within 24 hours in vagal se...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198509000-00005
更新日期:1985-09-01 00:00:00
abstract::An A and L system of neutral amino acid transport has been demonstrated previously in cerebral microvessels in vivo and in isolated microvessels in vitro. This report describes the neutral amino acid transport properties of cultured cerebral endothelial cells and investigates the influence of astroglia on the transpor...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198303000-00008
更新日期:1983-03-01 00:00:00
abstract::Primary central nervous system lymphomas (PCNSLs) are more resistant to radiotherapy and chemotherapy in AIDS (A-PCNSLs) than in non-AIDS patients (NA-PCNSLs). We investigated 23 A-PCNSLs and 24 NA-PCNSLs. Lymphoma cell kinetics (i.e. proliferation [mitotic index, MIB-1 and PCNA labeling indices], apoptosis and turnov...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-199910000-00005
更新日期:1999-10-01 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
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更新日期:2005-10-01 00:00:00
abstract::We have encountered a series of 8 third ventricular neoplasms with a distinctive chordoid appearance that appear to represent a clinicopathologic entity. The tumors occurred in 7 females and 1 male, ranging in age from 31 to 70 years. In all cases, imaging studies showed a large well-circumscribed third ventricular ma...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199803000-00009
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abstract::Inclusion body myositis (IBM) is a late-onset inflammatory myopathy with distinctive clinical and histopathological features. The molecular basis for the disease remains unknown, but abnormal nuclear morphology and the accumulation of a protein that binds single-stranded DNA in a sequence-independent fashion suggest a...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199805000-00003
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198409000-00008
更新日期:1984-09-01 00:00:00
abstract::Cerebral amyloid angiopathy (CAA), the deposition of beta-amyloid (Abeta3) in cerebral vessels, has been implicated as a common cause of hemorrhagic stroke and other forms of vascular disease. CAA is also a frequent concomitant of Alzheimer disease (AD). While the longterm consequences of CAA are well recognized from ...
journal_title:Journal of neuropathology and experimental neurology
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abstract::To develop improved therapies for medulloblastoma, we studied the ability of a neuroattenuated HSV-1 ICP34.5 mutant (variant-1716) to replicate within and destory an authentic medulloblastoma cell line known as Med 283 (D283) using immunohistochemistry, in situ hybridization, and viral titrations. In vitro studies sho...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199612000-00010
更新日期:1996-12-01 00:00:00
abstract::Calpain, a calcium-activated neutral protease family, has been implicated in the neuropathologic sequelae accompanying various neurological disorders. We have characterized the distribution and time course of calpain activation following brain injury in the rat, using a monoclonal antibody that recognizes calpain-gene...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199607000-00010
更新日期:1996-07-01 00:00:00
abstract::Genetic and lifestyle-related risk factors for Alzheimer disease (AD) are associated with an increase in oxidative stress, suggesting that oxidative stress is involved at an early stage of the pathologic cascade. Moreover, oxidative stress is mechanistically and chronologically associated with other key features of AD...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
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更新日期:2006-07-01 00:00:00
abstract::Since first described, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam has represented an important model of age-related neurodegenerative disease. ALS/PDC is characterized neuropathologically by severe widespread involvement by neurofibrillary tangles (NFTs). Over the past 30 years there...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.4.381
更新日期:2003-04-01 00:00:00
abstract::In a recent study we estimated the number and frequency distribution of the diameters of the cytons of all of the combined motoneuron columns of L3, L4 and L5 ventral horn of the spinal cord of man. In the present study we have estimated the number and frequency distribution of the diameter of motoneuron cytons in the...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197711000-00007
更新日期:1977-11-01 00:00:00
abstract::We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age....
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/63.9.911
更新日期:2004-09-01 00:00:00
abstract::Microglial activation and behavioral abnormalities occur before neuronal loss in experimental murine prion disease; the behavioral changes coincide with a reduction in synaptic plasticity. Because synaptic plasticity depends on an intact perineuronal net (PN), a specialized extracellular matrix that surrounds parvalbu...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181654386
更新日期:2008-03-01 00:00:00
abstract::The light and electron microscopic features of an unique retroperitoneal ganglioneuroblastoma in a four-year-old female are described. The unprecedented concurrence of Hirano, zebra, membranous cytoplasmic (MCB), and Pick bodies in the same population of neoplastic, sympathetic ganglion cells provides further evidence...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197601000-00002
更新日期:1976-01-01 00:00:00