1. IGF1 neuronal response in the absence of MECP2 is dependent on TRalpha 3
- Author
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de Souza, Janaina S, Carromeu, Cassiano, Torres, Laila B, Araujo, Bruno HS, Cugola, Fernanda R, Maciel, Rui MB, Muotri, Alysson R, and Giannocco, Gisele
- Subjects
Biological Sciences ,Genetics ,Neurosciences ,Pediatric ,Rare Diseases ,Stem Cell Research - Embryonic - Human ,Neurodegenerative ,Rett Syndrome ,Stem Cell Research ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Stem Cell Research - Induced Pluripotent Stem Cell ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Aetiology ,Underpinning research ,5.2 Cellular and gene therapies ,Development of treatments and therapeutic interventions ,Congenital ,Neurological ,Cell Differentiation ,Embryoid Bodies ,Humans ,Induced Pluripotent Stem Cells ,Insulin-Like Growth Factor I ,Methyl-CpG-Binding Protein 2 ,Neurodevelopmental Disorders ,Neuronal Plasticity ,Neurons ,Receptor ,IGF Type 1 ,Receptors ,Somatomedin ,Spine ,Synapses ,Thyroid Hormone Receptors alpha ,Transcriptome ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder in which the MECP2 (methyl CpG-binding protein 2) gene is mutated. Recent studies showed that RTT-derived neurons have many cellular deficits when compared to control, such as: less synapses, lower dendritic arborization and reduced spine density. Interestingly, treatment of RTT-derived neurons with Insulin-like Growth Factor 1 (IGF1) could rescue some of these cellular phenotypes. Given the critical role of IGF1 during neurodevelopment, the present study used human induced pluripotent stem cells (iPSCs) from RTT and control individuals to investigate the gene expression profile of IGF1 and IGF1R on different developmental stages of differentiation. We found that the thyroid hormone receptor (TRalpha 3) has a differential expression profile. Thyroid hormone is critical for normal brain development. Our results showed that there is a possible link between IGF1/IGF1R and the TRalpha 3 and that over expression of IGF1R in RTT cells may be the cause of neurites improvement in neural RTT-derived neurons.
- Published
- 2017