Specific pattern of maturation and differentiation in the formation of cortical tubers in tuberous sclerosis complex TSC: evidence from layer-specific marker expressionReport as inadecuate




Specific pattern of maturation and differentiation in the formation of cortical tubers in tuberous sclerosis complex TSC: evidence from layer-specific marker expression - Download this document for free, or read online. Document in PDF available to download.

Journal of Neurodevelopmental Disorders

, 8:9

First Online: 01 April 2016Received: 23 November 2015Accepted: 08 March 2016

Abstract

BackgroundTuberous sclerosis complex TSC is a multisystem disorder that results from mutations in the TSC1 or TSC2 genes, leading to constitutive activation of the mammalian target of rapamycin mTOR signaling pathway. Cortical tubers represent typical lesions of the central nervous system CNS in TSC. The pattern of cortical layering disruption observed in brain tissue of TSC patients is not yet fully understood, and little is known about the origin and phenotype of individual abnormal cell types recognized in tubers.

MethodsIn the present study, we aimed to characterize dysmorphic neurons DNs and giant cells GCs of cortical tubers using neocortical layer-specific markers NeuN, SMI32, Tbr1, Satb2, Cux2, ER81, and RORβ and to compare the features with the histo-morphologically similar focal cortical dysplasia FCD type IIb. We studied a cohort of nine surgically resected cortical tubers, five FCD type IIb, and four control samples using immunohistochemistry and in situ hybridization.

ResultsCortical tuber displayed a prominent cell loss in all cortical layers. Moreover, we observed altered proportions of layer-specific markers within the dysplastic region. DNs, in both tubers and FCD type IIb, were found positive for different cortical layer markers, regardless of their laminar location, and their immunophenotype resembles that of cortical projection neurons.

ConclusionsThese findings demonstrate that, similar to FCD type IIb, cortical layering is markedly disturbed in cortical tubers of TSC patients. Distribution of these disturbances is comparable in all tubers and suggests a dysmaturation affecting early and late migratory patterns, with a more severe impairment of the late stage of maturation.

KeywordsTuberous sclerosis complex Cortical layer markers Epilepsy Neurosurgery Neuropathology Electronic supplementary materialThe online version of this article doi:10.1186-s11689-016-9142-0 contains supplementary material, which is available to authorized users.

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Author: Angelika Mühlebner - Anand M. Iyer - Jackelien van Scheppingen - Jasper J. Anink - Floor E. Jansen - Tim J. Veersema -

Source: https://link.springer.com/







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