Altered Gene Expression of Thyroid Hormone Transporters and Deiodinases in iPS MeCP2-Knockout Cells-Derived Neurons

Autor(es)

de Souza, Janaina Sena ^{[1, 2]} ; Ferreira, Divino Romao ^[2] ; Herai, Roberto ^[3] ; Carromeu, Cassiano ^[1] ; Torres, Laila Brito ^{[4, 5]} ; Silva Araujo, Bruno Henrique ^[6] ; Cugola, Fernanda ^[1] ; Maciel, Rui M. B. ^[2] ; Muotri, Alysson Renato ^[1] ; Giannocco, Gisele ^{[2, 7]}

Afiliação do(s) autor(es)

^[1] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 - USA

^[2] Univ Fed Sao Paulo, Dept Med, Lab Endocrinol & Med Translac, UNIFESP EPM, Rua Pedro Toledo, 669-11 Andar, BR-04039032 Sao Paulo, SP - Brazil

^[3] Pontificia Univ Catolica Parana PUCPR PPGCS, Sch Med, Grad Program Hlth Sci, BR-80215901 Curitiba, Parana - Brazil

^[4] Inst Sao Leopoldo Mandic, Fac Sao Leopoldo Mandic, Farmacol, Area Fisiol, Campinas, SP - Brazil

^[5] Univ Sao Paulo, Human Genome & Stem Cell Res Ctr, Inst Biociences, Dept Genet & Evolutionary Biol, Sao Paulo, SP - Brazil

^[6] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil

^[7] Univ Fed Sao Paulo, Dept Ciencias Biol, UNIFESP, BR-09920000 Diadema, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 56, n. 12, p. 8277-8295, DEC 2019.
• Citações Web of Science: 0

Resumo

MeCP2 is an X-linked gene; its mutation causes Rett Syndrome (RTT), a severe neurodevelopmental disability that affects mainly girls. Acting as a transcription factor, the MeCP2 protein is able to regulate several hormone-related genes, such as the thyroid hormones (TH), which are known to play an important role in the development of the central nervous system (CNS). Although only a few studies have associated RTT and TH, TH deficit can lead to neurological deregulation by triggering functional deficiencies during adulthood. Here, we used human-induced pluripotent stem cell (iPSC) to generate MeCP2-knockout neuronal progenitor cells and adult neurons. Using this cellular model, we then investigated the expression of genes associated with TH homeostasis, such as the TH transporters (LAT1, LAT2, MCT8, MCT10, and OATP4A1) and deiodinases (DIO1, 2, and 3). Then, we treated the neural cells with THs and analyzed the expression of several genes related to neurodevelopment and functional maintenance. Our results showed that several TH-related genes, such as deiodinases, are altered in RTT samples when compared to WT cells. Moreover, the treatment of the neural cells with THs increased the amount of MAP2 and synapsin-1 expression in RTT cells. Our work provided evidences that TH homeostasis is compromised in RTT-derived neural cells, which could be an important factor to contribute to the imbalance in the neurodevelopmental phenotype presented in this syndrome and can lead us to better understand other neurodevelopmental diseases. (AU)

• Processo FAPESP: 17/07053-3 - Efeito do hormônio tiroidiano no encéfalo de camundongos 3xTg-AD, modelo da Doença de Alzheimer, no metabolismo da glicose e colesterol
• Beneficiário: Janaína Sena de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/08049-1 - Papel dos astrócitos na plasticidade sináptica de neurônios derivados de células tronco pluripotente induzidas de pacientes com Síndrome de Down
• Beneficiário: Bruno Henrique Silva Araujo Torres
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado