Transcription of intermediate filament genes is enhanced in focal cortical dysplasia

Taylor, J. Paul; Sater, Richard A.; French, Joyce M.; Baltuch, Gordon H.; Crino, Peter B.

doi:10.1007/s004010000348

Cited by 32 publications

(18 citation statements)

References 39 publications

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“…Specific protein expression patterns in FCD tissue correlated with age of seizure onset are not available, although many studies on the expression and/or upregulation of different kinds of proteins, including intermediate filaments, microtubule‐associated proteins, neurotrophins, tuberin, hamartin, and others within this tissue, have been reported 38–40, 43–49. Phospho‐S6 and p‐eIF4G do not appear to be expressed in an age‐dependent pattern in each dysplastic cortex (Groups I–III).…”

Section: Resultsmentioning

confidence: 99%

Insulin signaling pathways in cortical dysplasia and TSC‐tubers: Tissue microarray analysis

Miyata

Chiang

Vinters

2004

Annals of Neurology

138

134

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To evaluate the possible roles of the Akt/PKB-mTOR-p70S6K-S6 and cap-dependent translation (eIF4G) pathways in the pathogenesis of tuberous sclerosis complex (TSC)-associated cortical tubers and focal cortical dysplasia (FCD), we performed qualitative and semiquantitative immunohistochemical evaluation on surgically resected corticectomy specimens to detect phosphorylated molecules as activated downstream targets of the signaling pathways. A tissue microarray paraffin block was constructed from 63 archival specimens of surgically resected TSC tubers, FCDs with balloon cells, cortical dysplasia without balloon cells, and histologically normal-appearing neocortex obtained from cases with Rasmussen encephalitis, cystic-gliotic encephalopathy, and temporal lobe epilepsy. Abnormal neuroglial cells were positive for phospho-S6 and phospho-eIF4G with various staining intensities in FCDs and TSC tubers. Both proteins were much less abundantly expressed in normal-appearing neocortex. Phospho-mTOR expression was observed in neurons in all groups. The expression of phospho-S6 and phospho-eIF4G was associated with dysplastic lesions (p < 0.05), and the cytoplasmic phospho-p70S6K expression was most specific for and abundant in TSC tubers and much less prominent in other groups (p < 0.01). These results suggest that constitutive activation of cytoplasmic p70S6K plays a pivotal role in the pathogenesis of TSC tubers and that FCDs possess a distinct mechanism for activation of S6 and eIF4G.

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Section: Resultsmentioning

confidence: 99%

Insulin signaling pathways in cortical dysplasia and TSC‐tubers: Tissue microarray analysis

Miyata

Chiang

Vinters

2004

Annals of Neurology

138

134

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“…In addition, heterotopic neurons and gliosis are observed in the white matter (Mischel, 1995; Prayson, 1995; Prayson et al, 1996; Palmini et al, 2004). Giant neurons (also called meganeurons) apparently have a normal content of cytoplasmic organelles and, as in normal pyramidal cells, receive numerous symmetric synapses in cell body and proximal dendrites (Taylor et al, 2001).…”

Section: Research On Human Tissue Of Cortical Dysplasiamentioning

confidence: 99%

“…This is supported by the persistence of neuronal elements in the white matter lying between the periventricular region and the cortical mantle. These neurons were shown to exhibit various degrees of neuronal maturation as some cells showed characteristics of neuronal progenitors, such as nestin, undifferentiated neurons or glial cells exhibiting the presence of ß tubulin III (TUJ‐1), or vimentin, respectively, and others showing mixed neuronal and glial characteristics such as the coexpression of GFAP and neuronal nuclear (NeuN) and neuronal cytoskeletal proteins (microtubule associated proteins, MAP) (Garbelli et al, 1999; Taylor et al, 2001; Aronica et al, 2003; Fauser et al, 2004a; Ying, 2005). In addition, the persistence of neuronal elements (Cajal Retzius cells) in layer 1 of the neocortex was attributed to a failure of maturation of the cortical mantle through a problem in the apoptosis of these cells (Garbelli et al, 2001; Marin‐Padilla et al, 2002; Yun et al, 2003; Thom et al, 2005).…”

Section: Research On Human Tissue Of Cortical Dysplasiamentioning

confidence: 99%

Pathophysiological Mechanisms of Focal Cortical Dysplasia: A Critical Review of Human Tissue Studies and Animal Models

2007

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Summary:Cortical dysplasia (CD, also known as malformations of cortical development) are the pathological substrates in a large percentage of patients with pharmacoresistant epilepsy who may be amenable to surgical treatment. Therefore, research on the mechanisms of dysplastic lesion formation and epileptogenicity is of paramount importance for the prevention, detection, and treatment of CD-induced epilepsy. The purpose of this review is to discuss and critically evaluate the current state and results of human tissue experimentation (focusing on reported results of studies done on neocortical dysplastic tissue resected from patients with pharmacoresistant epilepsy), and to discuss some of the concerns related to research that uses surgically resected epileptic human tissue. The use of better animal models of CD as a tool toward the better understanding of the mechanisms of pathogenesis, epileptogenesis, and epileptogenicity of dysplastic lesions will be reviewed from the perspective of their usefulness in a model of translational research that should ultimately result in better diagnostic and therapeutic techniques of CD.

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“…Several authors had reported the expression of these intermediate filament proteins in the balloon cells (8,14–17). Furthermore, transcription of genes for nestin and vimentin was enhanced in the BCs (18). Over the past several years, much more attention has been focused on nestin.…”

mentioning

confidence: 99%

Expression of Neural Stem Cell Surface Marker CD133 in Balloon Cells of Human Focal Cortical Dysplasia

et al. 2005

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Summary: Purpose: Focal cortical dysplasia (CD) is characterized by the presence of dysmorphic neurons, laminar and columnar disorganization. A few patients with CD have balloon cells intermixed with dysmorphic neurons. The cellular characteristics of balloon cells remain unknown. This study was intended to determine further the cellular characteristics of balloon cells. Methods: Neocortical tissue resected from five patients with medically intractable focal epilepsy due to CD was studied. The presence of balloon cells (large opalescent cells with eccentric nuclei) was confirmed in all five patients by using cresylecht violet staining. Immunocytochemistry used antibodies against markers of pluripotential stem cells (CD133), multipotential progenitor cells (nestin), antiapoptotic gene products (Bcl‐2), immature neurons (β‐tubulin 3, TUJ1), immature glia (vimentin), mature neurons (MAP2 and NeuN), and astrocytes (glial fibrillary acidic protein; GFAP). Results: Balloon cells (BCs) were found to be immunoreactive to Bcl‐2 (46%), vimentin (41%), Nestin (28%), CD133 (28%), MAP2 (27%), GFAP (14%), and TUJ1 (10%). An extremely small number of BCs were immunopositive for NeuN. Confocal double labeling showed that balloon cells were dually immunopositive for CD133/nestin; CD133/GFAP; CD133/Bcl‐2, and nestin/GFAP. Conclusions: These results show that balloon cells are heterogeneous cell populations expressing cell‐surface markers for pluripotential stem cells and proteins for multipotent progenitors, or immature neurons/glia. The presence of stem cell/progenitor markers in the balloon cells could be due to a persistent postnatal neurogenesis or early embryonic insult that resulted in arrest of proliferation/differentiation at their early stages. Additionally, the coexpression of Bcl‐2 in CD133‐positive balloon cells suggests that a resistance to programmed cell death may be involved in the pathogenesis of cortical dysplasia.

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Transcription of intermediate filament genes is enhanced in focal cortical dysplasia

Cited by 32 publications

References 39 publications

Insulin signaling pathways in cortical dysplasia and TSC‐tubers: Tissue microarray analysis

Insulin signaling pathways in cortical dysplasia and TSC‐tubers: Tissue microarray analysis

Pathophysiological Mechanisms of Focal Cortical Dysplasia: A Critical Review of Human Tissue Studies and Animal Models

Expression of Neural Stem Cell Surface Marker CD133 in Balloon Cells of Human Focal Cortical Dysplasia

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