Abstract：
:The mechanisms underlying neurodegenerative diseases are the outcome of pathological alterations of evolutionary conserved molecular and cellular cascades. For this reason, Drosophila and C. elegans serve as useful model systems to study various aspects of neurodegenerative diseases. Here, we introduce the advantageous use of cultured Aplysia neurons (which express over 100 disease-related gene homologs shared with mammals), as a platform to study cell biological processes underlying the generation of tauopathy. Using live confocal imaging to follow cytoskeletal elements, autophagosomes, lysosomes, anterogradely and retrogradely transported organelles, complemented with electron microscopy, we demonstrate that the expression of mutant human tau in cultured Aplysia neurons leads to the development of hallmark Alzheimer disease (AD) pathologies. These include a reduction in the number of microtubules and their redistribution, impaired organelle transport, a dramatic accumulation of macro-autophagosomes and lysosomes, compromised neurite morphology and degeneration. Our study demonstrates the accessibility of the platform for long-term live imaging and quantification of subcellular pathological cascades leading to tauopathy. Based on the present study, it is conceivable that this system can also be used to screen for reagents that alter the pathological cascades.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Shemesh OA,Spira MEdoi
10.1007/s00401-010-0689-7subject
Has Abstractpub_date
2010-08-01 00:00:00pages
209-22issue
2eissn
0001-6322issn
1432-0533journal_volume
120pub_type
杂志文章abstract：:The original version of this article unfortunately contained a mistake. The Panel A in the published figure 5 is incorrect. The corrected Figure 5 is placed in the following page. ...
journal_title：Acta neuropathologica
pub_type： 已发布勘误
doi：10.1007/s00401-019-02092-y
更新日期：2020-01-01 00:00:00
abstract：:Although much work has been directed recently towards unravelling the protein chemistry of neurofibrillary tangle (NFT) and senile plaque (SP) components in Alzheimer's disease, the pathogeneses of these lesions remains largely unknown and the problem of their relationship is unresolved. In particular, although paired...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687379
更新日期：1989-01-01 00:00:00
abstract：:Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensor...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691784
更新日期：1979-10-01 00:00:00
abstract：:We present a case of progressive supranuclear palsy (PSP) with palatal myoclonus occurred in a 64-year-old man. The nucleus olivaris of the medulla oblongata showed high signal intensity on T2-weighted MR images, indicating brainstem tegmental atrophy, which were confirmed as hypertrophy of the nucleus inferior olivar...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050706
更新日期：1997-09-01 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：:Using a four-step immunoperoxidase (PAP) method and the monoclonal antibody MAbA9-C6 (MAbA9-C6), which defines an epitope of the retinal S-antigen (S-Ag), we investigated the S-Ag immunoreactivity in human fetal, newborn, infantile and adult pineal glands and in 13 human pineal parenchymal tumors. S-Ag immunoreactivit...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688043
更新日期：1986-01-01 00:00:00
abstract：:Collections of human postmortem brains gathered in brain banks have underpinned many significant developments in the understanding of central nervous system (CNS) disorders and continue to support current research. Unfortunately, the worldwide decline in postmortem examinations has had an adverse effect on research ti...
journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s00401-008-0360-8
更新日期：2008-05-01 00:00:00
abstract：:The cerebrovascular lesions of severe chronic hypertension were studied by light microscopy in perfusion-fixed, subserially sectioned brains from stroke-prone spontaneously hypertensive rats (SHRSP). The leakage and spread of plasma proteins were visualized by immunohistochemical detection of extravasated fibrinogen a...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690831
更新日期：1985-01-01 00:00:00
abstract：:Flurothyl-induced status epilepticus was studied by light and electron microscopy (LM, EM) to determine the time course and structural features of neuronal necrosis in the vulnerable brain regions in epilepsy. The cerebral cortex, hippocampus and thalamus were examined after closely spaced recovery periods of up to 1 ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687789
更新日期：1988-01-01 00:00:00
abstract：:An unusual case of concurrent MS and anaplastic astrocytoma is presented. MS was diagnosed in a female patient at the age of 22 years. A left side thalamotomy was performed for relief of severe intention tremor at age 28 and at age 32 she received immunosuppressive therapy for 1 year. At the age of 36 after a severe e...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690850
更新日期：1979-05-15 00:00:00
abstract：:The dynamics of cell-associated Concanavalin A (Con A) in astrocytes of the newborn rat (RNA), the rat glioma (AC), and the human glioblastoma (GB) were studied in vitro by fluorescence and electron microscopy. Con A receptors on the cell surface were seen usually as a continuous thin layer, and Con A accumulations in...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690804
更新日期：1982-01-01 00:00:00
abstract：:The Trembler mouse suffers from an hereditary demyelinating neuropathy. Schwann cell myelination of peripheral nerve fibres in the Trembler mouse is abnormal. Myelination of central nerve fibres in the deeper layers of white matter of the spinal cord is normal. At the junction between the peripheral nervous system and...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691273
更新日期：1977-04-29 00:00:00
abstract：:Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD) and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this study, we investigated the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque format...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00571510
更新日期：1995-01-01 00:00:00
abstract：:The occurrence of oligodendrocytes within astrocytes ("emperipolesis") has been described in demyelinating lesions in cases of multiple sclerosis and also in other non-demyelinating disorders. We found that this finding was common in the cerebral white matter of patients with Creutzfeldt-Jakob disease (CJD). Eight con...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-004-0880-9
更新日期：2004-09-01 00:00:00
abstract：:Multiple different pathological protein aggregates are frequently seen in human postmortem brains and hence mixed pathology is common. Mixed dementia on the other hand is less frequent and neuropathologically should only be diagnosed if criteria for more than one full blown disease are met. We quantitatively measured ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-015-1406-3
更新日期：2015-05-01 00:00:00
abstract：:Most cases of frontotemporal lobar degeneration (FTLD) are characterized by abnormal intracellular accumulation of either tau or TDP-43 protein. However, in ~10% of cases, composed of a heterogenous collection of uncommon disorders, the molecular basis remains to be uncertain. We recently discovered that the pathologi...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-010-0764-0
更新日期：2011-02-01 00:00:00
abstract：:We examined the immunohistochemical localization of p35nck5a, the regulatory subunit of cyclin-dependent kinase 5 (cdk5), in brains obtained postmortem from patients with Parkinson's disease (PD) and controls. We found p35nck5a immunoreactivity in Lewy bodies (LB) in the substantia nigra, locus ceruleus, and neocortex...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050687
更新日期：1997-08-01 00:00:00
abstract：:In this report, we describe the clinical, topographical and immunohistochemical characteristics of neurofilament (NF) inclusion formation induced by the intracisternal inoculation of young adult New Zealand white rabbits at 28-day intervals with 100 micrograms AlCl3 over the course of 267 days. The ability to recover ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00294460
更新日期：1995-01-01 00:00:00
abstract：:We have previously reported a pathological investigation of peripheral neuropathy in a horse with knuckling. This report describes details of the muscle and peripheral nerve lesions in two additional cases of light horse yearlings with knuckling. The skeletal muscles showed neurogenic atrophy characterized by scattere...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050916
更新日期：1998-10-01 00:00:00
abstract：:Evidence of misfolded wild-type superoxide dismutase 1 (SOD1) has been detected in spinal cords of sporadic ALS (sALS) patients, suggesting an etiological relationship to SOD1-associated familial ALS (fALS). Given that there are currently a number of promising therapies under development that target SOD1, it is of cri...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-016-1623-4
更新日期：2016-12-01 00:00:00
abstract：:Aluminum was observed in the nucleolus, interchromatin granules, rough endoplasmic reticulum, free ribosomes, euchromatin, and the heterochromatin of the neuron. The association of aluminum with the first four r-RNA-containing cellular components and with the last two DNA-containing chromatins suggests the association...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690191
更新日期：1985-01-01 00:00:00
abstract：:The pathological changes in the nucleus basalis of Meynert (nbM) in 10 autopsied cases with Pick's disease were studied in comparison with 15 age-matched controls. Both the number and density of nerve cells and the degree of fibrillary gliosis were examined at the anterior, intermediate, and posterior divisions of the...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687402
更新日期：1989-01-01 00:00:00
abstract：:A study of a muscle biopsy has provided evidence of storage involvement of the skeletal muscle fibres in Fabry's disease. In the endothelial cells of the capillaries, the inclusions were more abundant and pleomorphic. Muscle satellite cells were spared. In the sensory nerve biopsy, the perineurial and endothelial cell...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688064
更新日期：1977-06-15 00:00:00
abstract：:Amebic Meningoencephalitis (AM) and Primary Amebic Meningoencephalitis (PAM) are infectious diseases essentially confined to the Central Nervous System (CNS) and caused by free-living amebas of the genus Acanthamoeba (A.) and Naegleria (N.) respectively. AM due to A. sp. (Acanthamoeba castellanii and Acanthamoeba culb...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00686877
更新日期：1977-03-31 00:00:00
abstract：:The left and right recurrent laryngeal nerves and peroneal nerves from two groups of foals, one less than 1 month of age and the other 6 months of age, were examined by light and electron microscopy. While there was no evidence of fiber loss on light microscopy, occasional onion bulbs, regenerating clusters and swolle...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00227825
更新日期：1992-01-01 00:00:00
abstract：:Several cases of progressive multifocal leukoencephalopathy (PML) have been associated with simian virus 40 (SV40), rather than with JC virus (JCV), the polyomavirus originally isolated from PML tissue. PML has, therefore, been defined as a demyelinating syndrome with possible multiple viral etiologies. Tissues from t...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050894
更新日期：1998-09-01 00:00:00
abstract：:Interphase cytogenetics, i.e., in situ hybridization using probes to chromosome-specific DNA, enables histological identification of cells bearing numerical chromosome aberrations and cytogenetic analysis of composite tumors. We studied routinely processed tissues from seven glioblastomas and three gliosarcomas using ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00389493
更新日期：1994-01-01 00:00:00
abstract：:In a large series of 116 cortical resections for treatment of medically intractable epilepsy, 10 glial hamartomas and 11 neuronoglial malformative lesions were found. Glial hamartomas were astrocytic in 3 cases, oligodendrocytic in 6 and mixed oligoastrocytic in 1. Neuronoglial lesions corresponded to "focal cortical ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00296190
更新日期：1994-01-01 00:00:00
abstract：:The relationship between diabetes and the size, density and area of the ventromedial hypothalamic nucleus (VMH) was studied in the genetically diabetic Chinese hamster. Matched diabetic and non-diabetic control chinese hamsters were perfused, the hypothalamus collected, sectioned and stained for light microscopy. The ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691183
更新日期：1982-01-01 00:00:00
abstract：:The ultrastructure of the nervous tissue in a benign ovarian teratoma is described. This tissue was organized into areas having both "meningeal" and "ependymal" surfaces, between which were found astrocytes, ependymal cells, neurones with synapses and microglia. These cells all had ultrastructural similarities to thei...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00686623
更新日期：1987-01-01 00:00:00
