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：:Mouse central nervous system tissue cultured for different lengths of time was analyzed for the proliferation of macrophages. These cells were identified and characterized by ultrastructural features, cell surface determinants and their ability to ingest latex particles and bacteria. Under the experimental conditions ...
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：:Oxidative stress has been proposed as a potential mechanism for neurodegenerative diseases, such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). In response to oxidative stress, the levels of numerous cytoprotective products are increased via alteration of the Kelch-like ECH...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0b013e31827b5713
更新日期：2013-01-01 00:00:00
abstract：:Hydrocephalic hyh mice are born with moderate hydrocephalus and a normal cerebral aqueduct. At about the fifth postnatal day the aqueduct becomes obliterated and severe hydrocephalus develops. The aim of the present investigation was to investigate the mechanism of this hydrocephalus, probably starting during fetal li...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1093/jnen/60.11.1105
更新日期：2001-11-01 00:00:00
abstract：:Protein aggregate myopathies, including myofibrillar myopathies and sporadic inclusion body myositis (sIBM), are characterized by abnormal protein aggregates composed of various muscular and ectopic proteins. Previous studies have shown the crucial role ofdysregulated transcription factors such as neuron-restrictive s...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0b013e3181996d8f
更新日期：2009-03-01 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
pub_type： 杂志文章
doi：10.1093/jnen/nlw056
更新日期：2016-08-01 00:00:00
abstract：:We investigated whether antibody production to antigens arising in the subarachnoid space is depressed acutely after spinal cord injury (SCI), and whether such depression is due to abnormal catecholamine levels. To assess antibody responses, ovalbumin (OVA) was injected into the spinal subarachnoid space (i.t.) of rat...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1093/jnen/62.8.848
更新日期：2003-08-01 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
更新日期：1998-03-01 00:00:00
abstract：:Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed "asymptomatic AD subjects" (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingu...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0000000000000052
更新日期：2014-04-01 00:00:00
abstract：:The formation of Lewy bodies (LBs) and their relationship to other types of nigral inclusions associated with Parkinson disease (PD), such as pale bodies (PBs), remain poorly understood. Known constituents of LBs include alpha-synuclein (alphaS) and ubiquitin (Ub), providing windows to their morphogenesis. Additionall...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1093/jnen/62.12.1241
更新日期：2003-12-01 00:00:00
abstract：:Herpes simplex virus type 1 (HSV-1) is the cause of a serious and often fatal encephalitis. Patients who survive herpes simplex encephalitis (HSE) experience behavioral abnormalities including profound cognitive dysfunctions. We have developed a rat model of acute HSE to investigate the cognitive impairments caused by...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/00005072-199305000-00008
更新日期：1993-05-01 00:00:00
abstract：:It is recognized that IDH mutation negative, low-grade epilepsy associated tumors (LEAT) can show diffuse growth patterns and lack the diagnostic hallmarks of either classical dysembryoplastic neuroepithelial tumors (DNT) or typical ganglioglioma. "Nonspecific or diffuse DNT" and more recently "polymorphous low-grade ...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1093/jnen/nlx090
更新日期：2017-12-01 00:00:00
abstract：:Histological examination by light and electron microscopy of the spinal cords of four dogs rapidly perfusion-fixed after the onset of decompression sickness revealed the presence of numerous non-staining, space-occupying lesions that were absent in similarly prepared sections of control or ischemic spinal cords. We pr...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/00005072-198807000-00008
更新日期：1988-07-01 00:00:00
abstract：:Retraction of distal sensory axons is a prominent feature in diabetic peripheral neuropathy (DPN), a process amenable to insulin therapy. Nevertheless, diabetic patients and long-term diabetic mice develop motor deficits after longer durations of DPN, a process that may be related to insulin deficiency. To compare the...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0b013e318215669a
更新日期：2011-05-01 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：:The idiopathic inflammatory myopathies (IIMs) dermatomyositis, polymyositis, and inclusion body myositis are characterized by myofiber degeneration and inflammation. The triggering factors of muscle autoaggression in these disorders are unknown, but infiltrating T cells may be activated locally and proliferate in situ...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0b013e318177e5fd
更新日期：2008-06-01 00:00:00
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 u...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/00005072-199712000-00006
更新日期：1997-12-01 00:00:00
abstract：:Temporal lobe epilepsy (TLE) is characterized by hippocampal sclerosis together with profound losses and phenotypic changes of different classes of interneurons, including those expressing somatostatin (SRIF). To understand the functional significance of the plasticity of SRIF transmission in TLE, unraveling the statu...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/01.jnen.0000186923.50215.50
更新日期：2005-11-01 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：:Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammati...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0000000000000063
更新日期：2014-05-01 00:00:00
abstract：:Injury to neonatal nerves, unlike adult nerves, results in poor regeneration and extensive motoneuron death. We examined whether exposure to a more mature nerve environment could rescue axotomized motoneurons following neonatal injury. The sciatic nerve in 1 hindlimb of 3-day-old (P3) rats was transected and the cut e...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1093/jnen/62.1.75
更新日期：2003-01-01 00:00:00
abstract：:Large complex membranous bodies are described in the cerebral cortex of adult rats. Although these bodies are not very prevalent, they appear with increasing frequency as the age of the animal increases from 12 to 28 months. The membranous bodies are composed of varying amounts of membranes, cytoplasm and empty vacuol...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/00005072-197603000-00003
更新日期：1976-03-01 00:00:00
abstract：:Some agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma) belonging to the thiazolidinedione (TZD) family, as well as the cyclopentenone prostaglandin 15-dPGJ2, have been shown to cause neuroprotection in animal models of stroke. We have tested whether the TZD-unrelated PPARgamma agonist L-796,...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/01.jnen.0000178852.83680.3c
更新日期：2005-09-01 00:00:00
abstract：:In an effort to develop a method of tissue injury which would provide a model for the study of axonal regrowth in adult mammalian central nervous system (CNS), we have analyzed the effects of freezing in the dorsal columns of more than 200 rat spinal cords. The effects of temperature and time of exposure upon the size...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/00005072-198611000-00009
更新日期：1986-11-01 00:00:00
abstract：:Rupture of a saccular intracranial aneurysm (sIA) is often fatal. Thus, early detection of rupture-prone sIAs is vital. Myeloperoxidase (MPO), derived mainly from neutrophils, associates with sIA rupture, and therefore its role in sIA pathogenesis warrants further studies. We analyzed MPO and its association with othe...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1093/jnen/nly028
更新日期：2018-06-01 00:00:00
abstract：:Side population (SP) cells identified using the Hoechst 33342 fluorescent dye efflux technique overlap with the tumor stem cell fraction that is responsible for tumorigenesis and recurrence in malignant gliomas. Because diffuse invasion of glioma cells represents the main obstacle to successful therapy and underlies r...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0b013e3181e04739
更新日期：2010-06-01 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：:Cerebral accumulation of amyloid-beta (Abeta) is characteristic of Alzheimer disease and of amyloid precursor protein (APP) transgenic mice. Here, we assessed the efficacy of CI-1011, an inhibitor of acyl-coenzyme A:cholesterol acyltransferase, which is suitable for clinical use, in reducing amyloid pathology in both ...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0b013e3181e77ed9
更新日期：2010-08-01 00:00:00
abstract：:This is the fourth recorded patient with extension of syringomyelia into the brain rostral to the mesencephalon verified at autopsy. A syrinx was demonstrated from the low thoracic segments of the spinal cord to the cervico-medullary junction, where a fibrovascular malformation and dural-arachnoid adhesions deformed t...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/00005072-198111000-00005
更新日期：1981-11-01 00:00:00
abstract：:Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previous...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1093/jnen/nlw105
更新日期：2017-01-01 00:00:00
abstract：:The triplication of the DYRK1A gene encoding proline-directed serine/threonine kinase and located in the critical region of Down syndrome (DS) has been implicated in cognitive deficits and intellectual disability of individuals with DS. We investigated the effect of abnormal levels of this kinase on the cytoskeleton i...
journal_title：Journal of neuropathology and experimental neurology
pub_type： 杂志文章
doi：10.1097/NEN.0b013e31827733c8
更新日期：2012-12-01 00:00:00
