Impact of altered microbiota on brain development in mice: behavioral aspects

• Grant number: 17/03063-4
• Support type: Scholarships abroad - Research Internship - Scientific Initiation
• Effective date (Start): June 26, 2017
• Effective date (End): August 25, 2017
• Field of knowledge: Biological Sciences - Biology
• Principal researcher: Silvia Honda Takada
• Grantee: Talitha Amanda Sanches Bretherick
• Supervisor abroad: Alexander Drobyshevsky
• Home Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Research place: NorthShore University HealthSystem, United States
• Associated to the scholarship: 15/19699-0 - Efeitos da administração intrahipocampal de 2-APB na memória espacial e na ansiedade de ratos submetidos à anóxia neonatal, BP.IC

Abstract

Preterm infants are at high risk for later cognitive and behavioral deficits. Microbial community in infant guts, or microbiota, is acquired from the environment at birth and interacts to the maturing immune system. Perturbing initial colonization and microbiota development can affect brain development and post risk of developing neurological disorders later in life. Accumulating evidence and preliminary studies at the University of Chicago have suggested an association between gut microbiota and brain function. The overall aim of this study is to evaluate the impact of microbiota on early brain development and behaviors. We will use a novel mouse model. Human fecal samples will be obtained from preterm infants with normal or decreased weight gain at the University of Chicago neonatal intensive care unit and transplanted into germ-free pregnant mice. Age-matched germ free pups (with absence of microbiota) and pups treated with fecal transplants from human infants will be compared. Two time points in development will be investigated: pre-weaned mouse pups at two weeks of age and post-weaned pups at four weeks of age. To evaluate effect of different microbiota on brain development, we will use quantitative magnetic resonance imaging and histopathology to assess structural changes, myelination, axonal, and synaptic development. Open field, elevated maze test will be used to test social behavior and anxiety. Morris water maze for memory test and fear conditioning will be used to assess learning and memory. By carrying out these experiments, these studies will investigate how developmentally normal and altered microbiota might affect brain development and increase or reduce to reduce the risk of developing neurological diseases such as anxiety and depression and affect cognitive functions. (AU)