Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period

• Published in: Journal of neurodevelopmental disorders 2022-01, Vol.14 (1), p.8-8, Article 8
• Main Authors: Korotkov, Anatoly, Luinenburg, Mark J, Romagnolo, Alessia, Zimmer, Till S, van Scheppingen, Jackelien, Bongaarts, Anika, Broekaart, Diede W M, Anink, Jasper J, Mijnsbergen, Caroline, Jansen, Floor E, van Hecke, Wim, Spliet, Wim G, van Rijen, Peter C, Feucht, Martha, Hainfellner, Johannes A, Krsek, Pavel, Zamecnik, Josef, Crino, Peter B, Kotulska, Katarzyna, Lagae, Lieven, Jansen, Anna C, Kwiatkowski, David J, Jozwiak, Sergiusz, Curatolo, Paolo, Mühlebner, Angelika, van Vliet, Erwin A, Mills, James D, Aronica, Eleonora
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Analysis; Autism; Autism Spectrum Disorder - complications; Autism Spectrum Disorder - metabolism; Autopsy; Brain - metabolism; Brain research; Cell adhesion; Cell adhesion & migration; Cell culture; Cell differentiation; Cerebral cortex development; Child; Child, Preschool; Contactin; Contactins - genetics; Contactins - metabolism; Development and progression; Down-Regulation; Drug resistance; Epilepsy; Fetuses; Gene expression; Genes; Genetic disorders; Genetic transcription; Humans; Hybridization; Immunoglobulins; Immunohistochemistry; Infant; Infant, Newborn; Intellectual disabilities; Mental disorders; Middle Aged; mTORopathies; Nervous system diseases; Neuroblasts; Neurodevelopmental disorders; Polymerase chain reaction; Reverse transcription; Seizures; Seizures (Medicine); Transcriptomics; Tuberous sclerosis; Tuberous Sclerosis - complications; Tuberous Sclerosis - metabolism; Western blotting; Young Adult
• ISSN: 1866-1947; 1866-1955
• DOI: 10.1186/s11689-022-09416-2

The genetic disorder tuberous sclerosis complex (TSC) is frequently accompanied by the development of neuropsychiatric disorders, including autism spectrum disorder and intellectual disability, with varying degrees of impairment. These co-morbidities in TSC have been linked to the structural brain abnormalities, such as cortical tubers, and recurrent epileptic seizures (in 70-80% cases). Previous transcriptomic analysis of cortical tubers revealed dysregulation of genes involved in cell adhesion in the brain, which may be associated with the neurodevelopmental deficits in TSC. In this study we aimed to investigate the expression of one of these genes - cell-adhesion molecule contactin-3. Reverse transcription quantitative polymerase chain reaction for the contactin-3 gene (CNTN3) was performed in resected cortical tubers from TSC patients with drug-resistant epilepsy (n = 35, age range: 1-48 years) and compared to autopsy-derived cortical control tissue (n = 27, age range: 0-44 years), as well as by western blot analysis of contactin-3 (n = 7 vs n = 7, age range: 0-3 years for both TSC and controls) and immunohistochemistry (n = 5 TSC vs n = 4 controls). The expression of contactin-3 was further analyzed in fetal and postnatal control tissue by western blotting and in-situ hybridization, as well as in the SH-SY5Y neuroblastoma cell line differentiation model in vitro. CNTN3 gene expression was lower in cortical tubers from patients across a wide range of ages (fold change = - 0.5, p