Fine structure of atypical cells in tuberous sclerosis

Arseni, C; Alexianu, M; Horvat, L.; Alexianu, D; Petrovici, A

doi:10.1007/bf00688497

Cited by 33 publications

(5 citation statements)

References 16 publications

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“…cϪ SynICre ϩ mice Dysplastic enlarged neurons are a characteristic feature of human TSC tubers, in addition to giant cells (Arseni et al, 1972;Huttenlocher and Heydemann, 1984;Hirose et al, 1995;Crino, 2004;Miyata et al, 2004). Abundant Nissl substance and cytoskeleton abnormalities, such as abnormal cytoplasmic accumulation of argyrophilic fibrils and increased expression of neurofilament proteins, are the most prominent characteristics of dysplastic neurons in cortical tubers (Huttenlocher and Heydemann, 1984;Hirose et al, 1995).…”

Section: Patterns Of Neuronal Dysplasia Are Seen In Tsc1mentioning

confidence: 99%

A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival

Meikle

Talos²,

Onda³

et al. 2007

J. Neurosci.

411

421

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Section: Patterns Of Neuronal Dysplasia Are Seen In Tsc1mentioning

confidence: 99%

A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival

Meikle

Talos²,

Onda³

et al. 2007

J. Neurosci.

411

421

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“…Although previous reports have recognized the occurrence of various dysplastic cell types within tubers beyond the classical giant cell,4, 20, 21 we set out to classify the cellular pathology of these lesions in detail, using combined morphological and immunocytochemical criteria, including the use of neuronal and glial markers and phospho‐S6 (pS6) to assess the mammalian target of rapamycin (mTOR) pathway dysfunction. In addition, given that TSC is a malformation of development, we explored the hypothesis that the abnormal cell types present in tubers express immature iGluRs patterns known to promote cortical network hyperexcitability, thereby possibly contributing to the epileptogenicity of these lesions.…”

mentioning

confidence: 99%

Cell‐specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers

Talos

Kwiatkowski

Cordero

et al. 2008

Annals of Neurology

139

136

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Objective-Genetic loss of TSC1/TSC2 function in tuberous sclerosis complex (TSC) results in overactivation of the mammalian target of rapamycin complex 1 pathway, leading to cellular dysplasia. We hypothesized that the dysplastic cells in TSC tubers are heterogeneous, including separable classes on a neuronal-glial spectrum, and that these dysplastic cells express glutamate receptor (GluR) patterns consistent with increased cortical network excitability.Methods-Surgically resected human cortical tubers and nondysplastic epileptic cortical samples were analyzed by double-label immunocytochemistry for coexpression of neuronal and glial markers, the TSC1/TSC2 pathway downstream molecule phospho-S6 (pS6) and GluR subunits, and compared with control cortical tissue. Western blotting was used to quantify changes in GluR subunit expression in tubers versus controls.Results-We demonstrate that cortical tubers contain a broad spectrum of cell types including disoriented pyramidal cells, dysplastic neurons, giant neuroglial cells, dysplastic astroglia, and reactive astrocytes. Dysplastic neurons, giant cells, and dysplastic astroglia express high levels of pS6 and demonstrate altered GluR subunit composition, resembling those of normal immature neurons and glia. In contrast, nondysplastic neurons in TSC and non-TSC epileptic lesions express lower pS6 levels and display changes in GluR subunit expression that are distinct from the patterns seen in tuber dysplastic cells.Interpretation-This work significantly expands the spectrum of abnormal cells recognized in tubers beyond the classic tuber giant cell and demonstrates cell-specific abnormalities in GluR expression that may contribute to seizure pathogenesis in TSC. Furthermore, these results suggest that subunit-specific antagonists may be of potential use in the treatment of epilepsy in TSC.Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by inactivating mutations in either the TSC1 or TSC2 gene. 1,2 TSC brain lesions are malformations of cortical development that include cortical tubers, white matter abnormalities, subependymal nodules, Although previous reports have recognized the occurrence of various dysplastic cell types within tubers beyond the classical giant cell, 4,20,21 we set out to classify the cellular pathology of these lesions in detail, using combined morphological and immunocytochemical criteria, including the use of neuronal and glial markers and phospho-S6 (pS6) to assess the mammalian target of rapamycin (mTOR) pathway dysfunction. In addition, given that TSC is a malformation of development, we explored the hypothesis that the abnormal cell types present in tubers express immature iGluRs patterns known to promote cortical network hyperexcitability, thereby possibly contributing to the epileptogenicity of these lesions. White and coworkers 22 previously reported that dysplastic neurons and giant cells express abnormal patterns of glutamate and GABA receptor subunit messenger RNA. To further determine whether neurotrans...

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“…The ultrastructure of the cortical tuber in the brain (Arseni et al 1972) and of the angiomyolipoma in the kidneys (Mori et al 1971) has been reported in recent years in patients with T.S. However, to the best of our knowledge the fine structure of the angiofibromas of the skin in this syndrome has not been yet described.…”

Section: Discussionmentioning

confidence: 98%

Angiofibromas in Tuberous Sclerosis: A Lightand Electron Microscopic Study

Bhawan

Edelstein

1977

J Cutan Pathol

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Angiofibromas from two patients with tuberous sclerosis were studied by light and electron microscopy. Light microscopy revealed that these tumor-like nodules (which in the past have been called adenoma sebaceum) were made up of dilated capillaries, venules and arterioles embedded in connective tissue. At the ultrastructural level the arterioles embedded in connective tissue. At the ultrastructural level the endothelium of these vessels showed large numbers of microvilli on their luminal surface. The stroma contained many banded structures (so-called fibrous long spacing collagen). Myofibroblasts recently described in juvenile nasopharyngeal angiofibromas were not found in these angiofibromas of tuberous sclerosis.

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Fine structure of atypical cells in tuberous sclerosis

Cited by 33 publications

References 16 publications

A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival

A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival

Cell‐specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers

Angiofibromas in Tuberous Sclerosis: A Lightand Electron Microscopic Study

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