Abstract:
:By unknown mechanisms, the symptoms of amyotrophic lateral sclerosis (ALS) seem to spread along neuroanatomical pathways to engulf the motor nervous system. The rate at which symptoms spread is one of the primary drivers of disease progression. One mechanism by which ALS symptoms could spread is by a prion-like propagation of a toxic misfolded protein from cell to cell along neuroanatomic pathways. Proteins that can transmit toxic conformations between cells often can also experimentally transmit disease between individual organisms. To survey the ease with which motor neuron disease (MND) can be transmitted, we injected spinal cord homogenates prepared from paralyzed mice expressing mutant superoxide dismutase 1 (SOD1-G93A and G37R) into the spinal cords of genetically vulnerable SOD1 transgenic mice. From the various models we tested, one emerged as showing high vulnerability. Tissue homogenates from paralyzed G93A mice induced MND in 6 of 10 mice expressing low levels of G85R-SOD1 fused to yellow fluorescent protein (G85R-YFP mice) by 3-11 months, and produced widespread spinal inclusion pathology. Importantly, second passage of homogenates from G93A → G85R-YFP mice back into newborn G85R-YFP mice induced disease in 4 of 4 mice by 3 months of age. Homogenates from paralyzed mice expressing the G37R variant were among those that transmitted poorly regardless of the strain of recipient transgenic animal injected, a finding suggestive of strain-like properties that manifest as differing abilities to transmit MND. Together, our data provide a working model for MND transmission to study the pathogenesis of ALS.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Ayers JI,Fromholt S,Koch M,DeBosier A,McMahon B,Xu G,Borchelt DRdoi
10.1007/s00401-014-1342-7subject
Has Abstractpub_date
2014-12-01 00:00:00pages
791-803issue
6eissn
0001-6322issn
1432-0533journal_volume
128pub_type
杂志文章abstract::Extracellular deposition of amyloid β-protein (Aβ) in amyloid plaques and intracellular accumulation of abnormally phosphorylated τ-protein (p-τ) in neurofibrillary tangles (NFTs) represent pathological hallmark lesions of Alzheimer's disease (AD). Both lesions develop in parallel in the human brain throughout the pre...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-019-02053-5
更新日期:2019-12-01 00:00:00
abstract::Myotubular myopathy and centronuclear myopathies (CNM) are congenital myopathies characterized by generalized muscle weakness and mislocalization of muscle fiber nuclei. Genetically distinct forms exist, and mutations in BIN1 were recently identified in autosomal recessive cases (ARCNM). Amphiphysins have been implica...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-010-0754-2
更新日期:2011-02-01 00:00:00
abstract::Histochemical and electron microscopic studies were performed in an attempt to clarify the muscle pathology in an 18-year-old man with Fabry disease, showing proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00296520
更新日期:1995-01-01 00:00:00
abstract::A case of progressive polyneuropathy associated with Waldenström's macroglobulinaemia is reported. A monoclonal IgM-lambda gradient was detected in the serum and cerebro-spinal fluid. By electro-immunoblot analysis antibodies against myelin-associated glycoprotein were found in the serum and cerebro-spinal fluid. The ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690395
更新日期:1984-01-01 00:00:00
abstract::To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) mutation, we investigated the immunohistochemical localization of N(epsilon)-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050980
更新日期:1999-03-01 00:00:00
abstract::The present study used cocultures of rat dorsal root ganglia (DRG) and peritoneal macrophages to define the role of activated complement components during demyelination. The complement cascade was activated in vitro by treatment of the cultures with natural rat serum and lipopolysaccharides. Complement activation was ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00318572
更新日期:1995-01-01 00:00:00
abstract::The morphology of toxoplasma and its interaction with the cellular elements of the brain were studied in a patient who dies of extensive cerebral toxoplasmosis superimposed on Hodgkin's disease. The cerebral lesions were devoid of inflammatory cellular response and contained numerous organisms mostly in isolated multi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690360
更新日期:1978-06-30 00:00:00
abstract::The nuclei for the nerves of a dorsal (m. splenius) and a ventral (m. longus capitis) neck muscle of the rat were retrogradely labeled by applying horseradish peroxidase (HRP) to the respective cut muscle nerves. Motoneurons of both muscles were analyzed for their localization, diameter of perikarya, and area of dendr...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690368
更新日期:1981-01-01 00:00:00
abstract::We examined the effect of lactic acid on cultured human glioma cell lines expressing glial fibrillary acidic protein (GFAP), vimentin and neuron-specific enolase (NSE). The growth of the cells was inhibited by the lactic acid in a dose-dependent manner. At 56 mM of lactic acid, the surviving cells of the KNS-42-c2 cel...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00296110
更新日期:1990-01-01 00:00:00
abstract::Changes in morphology, behavior of the blood-brain barrier (BBB), regional cerebral blood flow (rCBF), and local cerebral glucose utilization (LCGU) were assessed and correlated in Mongolian gerbils following 5 min cerebral ischemia, produced by bilateral clamping of the common carotid arteries. The morphological chan...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691868
更新日期:1983-01-01 00:00:00
abstract::The quadriceps femoris muscles of experimental allergic myositis, in strain 13 guinea pigs immunised with rabbit myosin B fraction, were subjected to histochemical, immunohistochemical and electron microscopic studies. They demonstrated a variety of degenerative changes of muscle fibres, infiltration of lymphocytes an...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00692845
更新日期:1987-01-01 00:00:00
abstract::Axonal degeneration contributes to the transient and permanent neurological deficits seen in multiple sclerosis, an inflammatory disease of the central nervous system. To study the immunological mechanisms causing axonal degeneration, we induced experimental autoimmune encephalomyelitis (EAE) in wildtype Lewis rats an...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-006-0047-y
更新日期:2006-06-01 00:00:00
abstract::Conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of late onset sporadic Alzheimer's disease (LOAD). Mutations and/or differential expression of microglial specific receptors such as TREM2, CD33, and CR3 have been associated wi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-017-1737-3
更新日期:2017-11-01 00:00:00
abstract::Alterations in sphingolipid metabolism are described to contribute to various neurological disorders. We here determined the expression of enzymes involved in the sphingomyelin cycle and their products in postmortem brain tissue of multiple sclerosis (MS) patients. In parallel, we investigated the effect of the sphing...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-012-1014-4
更新日期:2012-09-01 00:00:00
abstract::Frontotemporal lobar degeneration is the term used to describe the non-Alzheimer clinical syndromes of frontotemporal dementia, semantic dementia and progressive non-fluent aphasia, regardless of the underlying neuropathological features. Considerable progress has been made in recent years in our understanding of the ...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-007-0241-6
更新日期:2007-07-01 00:00:00
abstract::Little information is available regarding the morphological changes in the mitochondria in amyotrophic lateral sclerosis (ALS). In particular, mitochondrial changes in dorsal root ganglion cells have not yet been examined. We therefore conducted an electron microscopic examination of the mitochondria in dorsal root ga...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-007-0299-1
更新日期:2007-12-01 00:00:00
abstract::In an autopsy case of the sporadic juvenile ALS (a 17-year-old girl) intracytoplasmic inclusions are found in the upper and lower motor neurons and in nerve cells of the dentate nucleus, pontine nucleus, brain stem reticular formation, substantia nigra, thalamus, globus pallidus and others. Histochemically they contai...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691069
更新日期:1978-12-15 00:00:00
abstract::Immunohistochemical analysis of inflammatory cell density and infiltrate subpopulations in 42 meningiomas was performed. Evaluation of infiltrating cell density was carried out by cell counting. Meningothelial and fibroblastic meningiomas contained an average of 3% mononuclear cells; the few lymphocytes were localized...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294381
更新日期:1989-01-01 00:00:00
abstract::This study tests the effects of chronic electrostimulation on denervated/reinnervated skeletal muscle in producing an optimal restoration of size and mechanical and histochemical properties. We compared tibialis anterior muscles in four groups of rats: in unoperated control (C) and 10 weeks following nerve lesion with...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-006-0035-2
更新日期:2006-06-01 00:00:00
abstract::A model of hypothermic circulatory arrest with recovery has been developed in the newborn dog. Eleven puppies were anesthetized with halothane, paralyzed and artificially ventilated with 70% nitrous oxide -30% oxygen to paO2 > 60 mm Hg, paCO2 = 33-42 mm Hg and pHa = 7.35-7.42. Animals were surface cooled to 20 degrees...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227767
更新日期:1993-01-01 00:00:00
abstract::Observations have been made on the structure of the paranodal region at nodes of Ranvier in the sural nerve of patients with diabetic sensory polyneuropathy. The structure of the paranodes was examined with particular attention to the definition and assessment of axoglial dysjunction, which has been claimed to be a ch...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050569
更新日期:1996-12-01 00:00:00
abstract::We report the case of an 11-year-old male who developed subacute diffuse polyradiculoneuropathy, associated with digestive symptoms and Epstein-Barr virus infection. Parental consanguinity was present. The laboratory findings including bone marrow smear were consistent with hemophagocytic lymphohistiocytosis (HLH). El...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-004-0897-0
更新日期:2004-10-01 00:00:00
abstract::We investigated whether the brainstem is affected by the pathologic process of sporadic Creutzfeldt-Jakob disease (sCJD), with particular attention to brainstem atrophy, neuronal loss, pyramidal tract degeneration, and prion protein (PrP) deposition, in 33 patients with sCJD. Brainstem atrophy, particularly in the pon...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-0981-0
更新日期:2005-06-01 00:00:00
abstract::We studied a case of primary leptomeningeal glioma (PLG) on the left parietal lobe of a 74-year-old woman and compared the tissue with heterotopic glial tissue from another case. The PLG tumor consisted of spindle-shaped cells with marked nuclear atypism, which tended to be arranged in a fascicular pattern, and the ma...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00310033
更新日期:1992-01-01 00:00:00
abstract::A complex neuropathological study of two cases of Niemann-Pick disease (NPD) type C (NPDC) revealed some novel features in the chemical pathology of the neuronal storage. Lipid histochemistry showed the presence of a lipid which met the criteria of a neuronal glycosphingolipid. Sphingomyelin (SM) was not detected in t...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690966
更新日期:1985-01-01 00:00:00
abstract::The most common cause of familial frontotemporal lobar degeneration with TAR DNA-binding protein-43 pathology (FTLD-TDP) has been found to be an expansion of a hexanucleotide repeat (GGGGCC) in a noncoding region of the gene C9ORF72. Hippocampal sclerosis (HpScl) is a common finding in FTLD-TDP. Our objective was to s...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-013-1161-2
更新日期:2013-10-01 00:00:00
abstract::In order to further evaluate the parameters whereby intracerebral administration of recombinant α-synuclein (αS) induces pathological phenotypes in mice, we conducted a series of studies where αS fibrils were injected into the brains of M83 (A53T) and M47 (E46K) αS transgenic (Tg) mice, and non-transgenic (nTg) mice. ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-014-1268-0
更新日期:2014-05-01 00:00:00
abstract::Aberrant peripheral nerve fiber bundles, i.e., masses of peripheral nerve fibers without perineural sheath cells, are found in the perivascular spaces of some spinal cords. The 514 spinal cords examined for these structures were separated into two groups; 507 spinal cords without definite necrotic lesions (group 1) an...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00308951
更新日期:1989-01-01 00:00:00
abstract::The IgM fraction of normal swine serum (NSS) was found to adhere to human peripheral nerve myelin sheaths from randomly selected neuropathies and control nerves in electron microscopic immunocytochemical assays. The reaction could be blocked by preincubation with undiluted fetal calf serum (FCS), whereas endoneurial b...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688249
更新日期:1988-01-01 00:00:00
abstract::A series of 50 human primary intracranial tumors were cultivated in vitro in an attempt to establish cell lines with the trypsinization technique. During the in vitro adaptation period, cultures were maintained at high cell density to avoid rapid over-growth by connective tissue. Five lines were established from 5 tum...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690383
更新日期:1977-07-15 00:00:00