The role of astrocytes in the synaptic plasticity of neurons derived from induced pluripotent stem cells from Down Syndrome patients

• Grant number: 14/08049-1
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): July 01, 2014
• Effective date (End): January 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ésper Abrão Cavalheiro
• Grantee: Bruno Henrique Silva Araujo Torres
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Among the genetic changes related to Intellectual Disabilities ( ID) the most well characterized is Down syndrome (DS ) , whose subjects have the presence of an extra 21 chromosome. The DS patients have motor and cognitive impairments such as reduction in the coefficient of memory, learning and language disabilities . Much of what we understand today about the implication of trisomy 21 in the development , electrophysiological and morphological properties of the Central Nervous System ( CNS ) came from studies conducted in animal models . However , the experiments of cell reprogramming led by Japanese researcher Shinya Yamanaka , opened up a new experimental approach , which may provide a better understanding of the changes caused by the extra copy of chromosome 21 . The reported cognitive deficits in patients with DS have been associated mainly with macro and micro structural changes during development of the CNS. Evidence shows that astrocytes are major players in the maturation of the nervous system , they effectively modulate all stages of the formation and maturation of synapses . In this sense , our study proposes the analysis of the influence of astrocytes in synaptic modulation in cultured neurons from patients with DS , in order to enable a better understanding of the role of astrocytes in the signaling pathways involved in the maintenance and maturation of the mammalian CNS of DS individuals.

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ARAUJO, BRUNO H. S.; KAID, CAROLINI; DE SOUZA, JANAINA S.; DA SILVA, SERGIO GOMES; GOULART, ERNESTO; CAIRES, LUIZ C. J.; MUSSO, CAMILA M.; TORRES, LAILA B.; FERRASA, ADRIANO; HERAI, ROBERTO; et al. Down Syndrome iPSC-Derived Astrocytes Impair Neuronal Synaptogenesis and the mTOR Pathway In Vitro. Molecular Neurobiology, v. 55, n. 7, p. 5962-5975, JUL 2018. (15/14821-1, 17/16283-2, 13/08028-1, 14/08049-1)

DE SOUZA, JANAINA S.; CARROMEU, CASSIANO; TORRES, LAILA B.; ARAUJO, BRUNO H. S.; CUGOLA, FERNANDA R.; MACIEL, RUI M. B.; MUOTRI, ALYSSON R.; GIANNOCCO, GISELE. IGF1 neuronal response in the absence of MECP2 is dependent on TRalpha 3. Human Molecular Genetics, v. 26, n. 2, p. 270-281, JAN 15 2017. (14/08049-1)

DE SOUZA, JANAINA SENA; FERREIRA, DIVINO ROMAO; HERAI, ROBERTO; CARROMEU, CASSIANO; TORRES, LAILA BRITO; SILVA ARAUJO, BRUNO HENRIQUE; CUGOLA, FERNANDA; MACIEL, RUI M. B.; MUOTRI, ALYSSON RENATO; GIANNOCCO, GISELE. Altered Gene Expression of Thyroid Hormone Transporters and Deiodinases in iPS MeCP2-Knockout Cells-Derived Neurons. Molecular Neurobiology, v. 56, n. 12, p. 8277-8295, DEC 2019. (17/07053-3, 14/08049-1)

KAID, CAROLINI; GOULART, ERNESTO; CAIRES-JUNIOR, LUIZ C.; ARAUJO, BRUNO H. S.; SOARES-SCHANOSKI, ALESSANDRA; BUENO, HELOISA M. S.; TELLES-SILVA, KAYQUE A.; ASTRAY, RENATO M.; ASSONI, AMANDA F.; JUNIOR, ANTONIO F. R.; et al. Zika Virus Selectively Kills Aggressive Human Embryonal CNS Tumor Cells In Vitro and In Vivo. Cancer Research, v. 78, n. 12, p. 3363-3374, JUN 15 2018. (15/14821-1, 16/09707-8, 17/16283-2, 14/08049-1, 13/08028-1)

SILVA ARAUJO, BRUNO HENRIQUE; TORRES, LAILA BRITO; GUILHOTO, LAURA MARIA F. F.. Cerebal overinhibition could be the basis for the high prevalence of epilepsy in persons with Down syndrome. Epilepsy & Behavior, v. 53, p. 120-125, DEC 2015. (14/08049-1)

KAID, CAROLINI; JORDAN, DIONE; DE SIQUEIRA BUENOS, HELOISA MARIA; SILVA ARAUJO, BRUNO HENRIQUE; ASSONI, AMANDA; OKAMOTO, OSWALDO KEITH. miR-367 as a therapeutic target in stem-like cells from embryonal central nervous system tumors. MOLECULAR ONCOLOGY, v. 13, n. 12, AUG 2019. (13/08028-1, 13/02983-1, 16/09707-8, 14/08049-1)