Abstract：
:Focal cortical dysplasia (FCD) is a localized malformation of cortical development and is the commonest cause of severe childhood epilepsy in surgical practice. Children with FCD are severely disabled by their epilepsy, presenting with frequent seizures early in life. The commonest form of FCD in children is characterized by the presence of an abnormal population of cells, known as balloon cells. Similar pathological changes are seen in the cortical malformations that characterize patients with tuberous sclerosis complex (TSC). However, the cellular and molecular mechanisms that underlie the malformations of FCD and TSC are not well understood. We provide evidence for a defect in autophagy in FCD and TSC. We have found that balloon cells contain vacuoles that include components of the autophagy pathway. Specifically, we show that balloon cells contain prominent lysosomes by electron microscopy, immunohistochemistry for LAMP1 and LAMP2, LysoTracker labelling and enzyme histochemistry for acid phosphatase. Furthermore, we found that balloon cells contain components of the ATG pathway and that there is cytoplasmic accumulation of the regulator of autophagy, DOR. Most importantly we found that there is abnormal accumulation of the autophagy cargo protein, p62. We show that this defect in autophagy can be, in part, reversed in vitro by inhibition of the mammalian target of rapamycin (mTOR) suggesting that abnormal activation of mTOR may contribute directly to a defect in autophagy in FCD and TSC.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Yasin SA,Ali AM,Tata M,Picker SR,Anderson GW,Latimer-Bowman E,Nicholson SL,Harkness W,Cross JH,Paine SM,Jacques TSdoi
10.1007/s00401-013-1135-4subject
Has Abstractpub_date
2013-08-01 00:00:00pages
207-18issue
2eissn
0001-6322issn
1432-0533journal_volume
126pub_type
杂志文章abstract：:Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-011-0802-6
更新日期：2011-03-01 00:00:00
abstract：:Emerging evidence has demonstrated the neuroprotection of estrogen in Alzheimer's disease (AD). The hippocampus, an important target of estrogen action, is severely affected in the Alzheimer process. The aim of present study was to detect the distribution of estrogen receptor-alpha (ER-alpha) and the relationship betw...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-003-0720-3
更新日期：2003-09-01 00:00:00
abstract：:A 1-year-old male chinchilla with a 2-week history of conjunctivitis suffered subsequently from neurological signs comprising seizures, disorientation, recumbency and apathy. After 3 weeks of progressive central nervous disease the animal was killed in view of the poor prognosis. A non-suppurative meningitis and polio...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-002-0597-6
更新日期：2002-12-01 00:00:00
abstract：:Neurofibrillary tangles were induced in the motor neurons of the rabbit spinal cord by the intrathecal injection of colchicine, vinblastine, and vincristine. The tangles stained intensely by immunofluorescence and by the peroxidase-anti-peroxidase procedure using neurofilament antisera raised against chicken brain ant...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690460
更新日期：1980-01-01 00:00:00
abstract：:We recently examined the brain from an 8-month-old infant with Down's syndrome and found argyrophilic plaque-like deposits throughout the neocortex and cerebellum. To ascertain the specificity of this observation, we examined 27 additional brains from the pediatric autopsy service, including 1 from another patient wit...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00294258
更新日期：1995-01-01 00:00:00
abstract：:Data on the relationship between Parkinson's disease (PD) and stroke have been conflicting, some studies showing a reduced risk of stroke during life, and others indicating an increased risk of stroke-related death. Consecutive cases (n=617) of autopsy-proven idiopathic PD (Lewy body disease of the brain stem type) an...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-003-0676-3
更新日期：2003-05-01 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：:Neuronal and glial cytoplasmic inclusions (NCIs and GCIs), which contain alpha-synuclein as a major component, are characteristic cytopathological features of multiple system atrophy (MSA). We report MSA of 19 years' duration in a 73-year-old woman. Her initial symptom was parkinsonism, with dementia appearing about 8...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010000292
更新日期：2001-03-01 00:00:00
abstract：:Numbers of synapses were counted in columns of neuropil orientated at right angles to the pia in frontal and temporal regions from postmortem brains. In the frontal region of 28 patients aged 26-90 years there were 1.2 X 10(8) mm3 (SD 0.03 X 10(8], and in the temporal of 18 patients aged 16-90 years there were 1.4 X 1...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00684929
更新日期：1983-01-01 00:00:00
abstract：:An 18 month old cat had a 6 month history of abnormal high stepping gait, ataxia, muscle twitching and loss of sensory perception. The clinical course was interrupted by several episodes of temporary remission. The essential pathological features were those of a polyradiculoneuritis with segmental demyelination, focal...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00689561
更新日期：1978-01-19 00:00:00
abstract：:The nature and distribution of vascular changes in acute Wernicke's encephalopathy (WE) were analyzed in three autopsy cases. Lesions of the lateral vestibular nucleus of the medulla oblongata (three cases) and lateral ventricular wall (one case) were examined by reconstruction of 200 serial sections, and the capillar...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00307646
更新日期：1995-01-01 00:00:00
abstract：:The topographic distribution of brain atrophy was quantified by image analysis of fixed coronal brain slices from four patients dying with cortical Lewy body disease (CLBD) all with Alzheimer-type pathology and compared to that in four other patients of similar age and gender dying with Alzheimer's disease (AD) alone....
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00296363
更新日期：1995-01-01 00:00:00
abstract：:Macroautophagy is a dynamic process whereby cytoplasmic components are initially sequestered within autophagosomes. Recent studies have shown that the autophagosome membrane can selectively recognize ubiquitinated proteins and organelles through interaction with adapter proteins such as p62 and NBR1. Both proteins are...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-012-0975-7
更新日期：2012-08-01 00:00:00
abstract：:In the nerve tissue with proliferating macroglia cells were observed a lowered oxygen consumption, an increased aerobic glycolysis and alanine formation and a higher alanine aminotransferase and glutamate dehydrogenase activity than in the control tissue in the homogenates and in the cell sap fraction. The substrate s...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00684665
更新日期：1976-03-15 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：:The authors present the case of a hypertensive patient with a thrombosis of a saccular microaneurysm (SMA) and underlying cerebral (pontine) lacunae. This SMA lay at the junction between the main vessel and two small feeding arteries penetrating into the necrotic territory. Microhemorrhages were observed in and outsid...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688313
更新日期：1986-01-01 00:00:00
abstract：:Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-007-0231-8
更新日期：2007-08-01 00:00:00
abstract：:The binding of carbon disulphide sulphur was studied in the spinal cord and its axons of four control and four phenobarbitone pretreated adult rats 3 and 6 h after an intraperitoneal injection of 650 mumol of CS2 in olive oil. The binding of CS2 carbon was measured in the same fractions of two adult control rats 4.5 h...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00685369
更新日期：1976-11-15 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：:Virtually all phases of spinal cord injury pathogenesis, including inflammation, cell proliferation and differentiation, as well as tissue remodeling, are mediated in part by infiltrating monocyte-derived macrophages. It is now clear that these infiltrating macrophages have distinct functions from resident microglia a...
journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s00401-019-01992-3
更新日期：2019-05-01 00:00:00
abstract：:Keratan sulphate proteoglycan (KSPG) is a developmentally regulated barrier molecule, directing axonal growth during central nervous system (CNS) formation. The possible re-expression and functional significance of KSPG in preventing axon regeneration following spinal cord injury (SCI) is poorly understood. In the pre...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-002-0589-6
更新日期：2002-12-01 00:00:00
abstract：:Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and 'adult-type' diffuse gliomas, are largely established, those of uncommon LGNTs remain to be define...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-016-1539-z
更新日期：2016-06-01 00:00:00
abstract：:Mislocalization and abnormal deposition of TDP-43 into the cytoplasm (TDP-43 proteinopathy) is a hallmark in neurons of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the pathogenic mechanism of the diseases linked to TDP-43 is largely unknown. We hypothesized that the failu...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-020-02205-y
更新日期：2020-11-01 00:00:00
abstract：:Gliomatosis cerebri (GC), a rare and deadly CNS neoplasm characterized by involvement of at least three cerebral lobes, predominantly affects adults. While a few small series have reported its occurrence in children, little is known about the molecular characteristics of pediatric GC. We reviewed clinical, radiologica...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-015-1532-y
更新日期：2016-02-01 00:00:00
abstract：:Histopathological, immunocytochemical, and electron microscopical investigations were carried out in a man with a protracted history of spastic paraparesis, adrenal insufficiency and hypogonadism. Pathological findings were identical with those of the few previously reported cases of adrenomyeloneuropathy (AMN) includ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690750
更新日期：1980-01-01 00:00:00
abstract：:This study was undertaken to elucidate morphological changes in the synaptic area of the Purkinje cell dendritic spines when granule cells were decreased in number. The mice were injected s.c. with 30 mg/kg b.w. of cytosine arabinoside on days 2, 3, and 4, and on days 7, 8 and 9, and were designated as group I and gro...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00685343
更新日期：1983-01-01 00:00:00
abstract：:Two cases out of a sample of 41 fetuses and infants with prosencephalic malformation, observed at the Institute of Pathology and Department of Neuropathology of the University of Heidelberg, are described here in detail. These cases presented grossly with microcephaly and missing forebrain, appearing to be cases of ap...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/pl00007438
更新日期：2000-03-01 00:00:00
abstract：:Methylmercury (MeHg) poisoning (20 mg/kg body weight) in embryonic mice resulted in significant reductions of mitotic indices in the neuroepithelial germinal cells of the telencephalon at the ventricular surface 4 to 12 h following intoxication. After 24 h, no significant difference in the mitotic indices was observed...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00293454
更新日期：1991-01-01 00:00:00
abstract：:Exercise intolerance associated with myalgias, muscle cramps or myoglobinuria may be associated with a dystrophinopathy. A search for abnormal dystrophin expression (using immunohistochemistry, immunoblot and DNA analysis) was carried out in a series of 15 patients. They were selected because they presented exercise i...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050671
更新日期：1997-07-01 00:00:00
abstract：:The suprascapular nerve from 14 horses, which had no clinical evidence of spinatus muscle atrophy, were obtained to determine whether the nerve was sub-clinically compressed at the scapular edge. The nerves were divided into three portions, proximal and distal to the scapular edge and as it reflected around it. In nin...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688338
更新日期：1987-01-01 00:00:00
