Cell modeling Autism Spectrum Disorder patients using induced pluripotent stem cells (iPSC)

• Grant number: 16/02978-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2016
• End date: June 30, 2019
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Patricia Cristina Baleeiro Beltrão Braga
• Grantee: Fabiele Baldino Russo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Studying autism biology is a challenge due to the lack of access to patients cells from the central nervous system (CNS). Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with high functional impairment, where patients exhibit behavioral changes as repetitive and ste-reotyped movements, communication deficits and socialization problems. The worldwide prevalence of ASD is very high, with about 1% of the world population. The diagnosis of ASD patients usually occurs at three years of age and is more common in boys. In 2007 a technology to generate pluripotent stem cells from human somatic cells (iPSC) was described by Takahashi & Yamanaka. This important tool, opened doors to generate cel-lular models to study disease in vitro. Our group has been carrying out idiopathic autism modeling in vitro, to identify and study some neuronal phenotypes. Among our preliminary results, we managed to get some data that led us to believe that not only neurons, but also astrocytes from CNS of patients with ASD represent a key role in the development of autistic phenotype. In general, glia are responsible for CNS maintenance, control neurogenesis, synaptogenesis support to make the maintenance of synapses and support and nutrition to neurons. According to our preliminary results, astrocytes from neurotypicals individuals (controls) were able to partially rescue the phenotype of neurons of patients with ASD. Based on these data, this project tends to investigate in vitro the role of astrocytes in the interaction with neurons in patients with ASD, seeking to identify possible relevant routes responsible for the autism phenotype. Still, with the transplantation of healthy astrocytes in animal models of autism, we plan to verify if is possible to change or even rescue the autistic phenotype in vivo. (AU)

Scientific publications

(7)

(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)

YDE OHKI, CRISTINE MARIE; BENAZZATO, CECILIA; RUSSO, FABIELE BALDINO; BALEEIRO BELTRAO-BRAGA, PATRICIA CRISTINA. Developing animal models of Zika virus infection for novel drug discovery. EXPERT OPINION ON DRUG DISCOVERY, v. 14, n. 6, APR 2019. (18/16748-8, 16/02978-6)

ROSA-FERNANDES, LIVIA; CUGOLA, FERNANDA RODRIGUES; RUSSO, FABIELE BALDINO; KAWAHARA, REBECA; DE MELO FREIRE, CAIO CESAR; CORREA LEITE, PAULO EMLIO; BASSI STERN, ANA CAROLINA; ANGELI, CLAUDIA BLANES; LEAL DE OLIVEIRA, DANIELLE BRUNA; MELO, STELLA REZENDE; et al. Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 13, MAR 15 2019. (16/02978-6, 14/06863-3, 13/08844-3, 18/16748-8, 11/20683-0, 15/02866-0)

BENAZZATO, CECILIA; RUSSO, FABIELE BALDINO; BELTRAO-BRAGA, PATRICIA CRISTINA BALEEIRO. An update on preclinical pregnancy models of Zika virus infection for drug and vaccine discovery. EXPERT OPINION ON DRUG DISCOVERY, v. 17, n. 1, SEP 2021. (18/16748-8, 16/02978-6)

LEITE, PAULO EMILIO CORREA; PORTES, JULIANA DE ARAUJO; PEREIRA, MARIANA RODRIGUES; RUSSO, FABIELE BALDINO; MARTINS-DUARTE, ERICA S.; DOS SANTOS, NATHALIA ALMEIDA; ATTIAS, MARCIA; BARRANTES, FRANCISCO J.; BELTRAO-BRAGA, PATRICIA CRISTINA BALEEIRO; DE SOUZA, WANDERLEY. Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, v. 11, p. 11-pg., 2021-02-01. (16/02978-6, 18/16748-8)

RUSSO, FABIELE BALDINO; BRITO, ANITA; DE FREITAS, ARIANE MIRANDA; CASTANHA, ANDRELISSA; DE FREITAS, BEATRIZ C.; BALEEIRO BELTRAO-BRAGA, PATRICIA CRISTINA. The use of iPSC technology for modeling Autism Spectrum Disorders. Neurobiology of Disease, v. 130, OCT 2019. (11/20683-0, 16/02978-6)

RUSSO, FABIELE BALDINO; FREITAS, BEATRIZ CAMILLE; PIGNATARI, GRACIELA CONCEICAO; FERNANDES, ISABELLA RODRIGUES; SEBAT, JONATHAN; MUOTRI, ALYSSON RENATO; BALEEIRO BELTRAO-BRAGA, PATRICIA CRISTINA. Modeling the Interplay Between Neurons and Astrocytes in Autism Using Human Induced Pluripotent Stem Cells. BIOLOGICAL PSYCHIATRY, v. 83, n. 7, p. 569-578, APR 1 2018. (11/20683-0, 16/02978-6)

BRITO, ANITA; FRANCO, FELIPE; BRENTANI, HELENA; BELTRAO-BRAGA, PATRICIA CRISTINA BALEEIRO. Assessment of vulnerability dimensions considering Family History and environmental interplay in Autism Spectrum Disorder. BMC Psychiatry, v. 23, n. 1, p. 13-pg., 2023-04-14. (16/02978-6, 18/16748-8)