Impact of neuroinflammation and the participation of the gut-brain axis in myelination in a rodent model of neonatal anoxia combined with perinatal inflammation by maternal immune activation

• Grant number: 20/16268-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2022
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Silvia Honda Takada
• Grantee: Silvia Honda Takada
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Oxygen deprivation at birth, known clinically as neonatal anoxia or perinatal asphyxia, is considered one of the major causes of neonatal deaths in the world and one of the main risk factors for several neurodevelopmental disorders in individuals who survive this condition, generating considerable impact in public health. One of the main risk groups for the occurrence of neonatal anoxia are premature infants with low birth weight, and in most cases, premature birth is triggered by maternal inflammation. Models of maternal immune activation (MIA) in rodents showed important behavioral changes consistent with some neurodevelopmental diseases, such as autism spectrum disorder (ASD) and we believe that sensitization caused by MIA can potentiate the effects of neonatal anoxia in our already validated and well established rodent model, which mimics oxygen deprivation in premature individuals. In addition, as both are systemic stimuli, we believe that there may be changes in the permeability of the intestinal barrier due to neuroinflammation and, based on recent advances in studies of the participation of the gut-brain axis in inflammatory processes, such changes would further potentiate the deleterious effects of neuroinflammation. Therefore, in order to establish the understanding of the mechanisms that lead to molecular, cellular, histological and cognitive changes observed as sequelae of neonatal anoxia, the hypothesis of this project is that changes in the intestinal level caused by anoxic stimulus combined to perinatal inflammation may influence the persistence and increase of the inflammatory process established in the CNS, altering important neurodevelopment processes, such as myelination, reflecting in changes in behavior, consistent with ASD. (AU)

Scientific publications

(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)

FABRES, RAFAEL BANDEIRA; CARDOSO, DEBORA STERZECK; ARAGON, BRIAN ARANIBAR; ARRUDA, BRUNA PETRUCELLI; MARTINS, PAMELA PINHEIRO; IKEBARA, JULIANE MIDORI; DROBYSHEVSKY, ALEXANDER; KIHARA, ALEXANDRE HIROAKI; DE FRAGA, LUCIANO STURMER; NETTO, CARLOS ALEXANDRE; et al. Consequences of oxygen deprivation on myelination and sex-dependent alterations. Molecular and Cellular Neuroscience, v. 126, p. 11-pg., 2023-06-03. (20/16268-6)

MARINHO, LUCIANA SIMOES RAFAGNIN; CHIARANTIN, GABRIELLY MARIA DENADAI; IKEBARA, JULIANE MIDORI; CARDOSO, DEBORA STERZECK; DE LIMA-VASCONCELLOS, THEO HENRIQUE; HIGA, GUILHERME SHIGUETO VILAR; FERRAZ, MARIANA SACRINI AYRES; DE PASQUALE, ROBERTO; TAKADA, SILVIA HONDA; PAPES, FABIO; et al. The impact of antidepressants on human neurodevelopment: Brain organoids as experimental tools. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 144, p. 10-pg., 2023-03-17. (19/17892-8, 20/16268-6, 20/11451-7, 20/02035-0, 21/11969-9, 20/11667-0, 19/15024-9, 16/17329-3)