Banca de DEFESA: PAMELA PINHEIRO MARTINS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : PAMELA PINHEIRO MARTINS
DATE: 18/10/2023
TIME: 14:00
LOCAL: Sala 208 do Bloco Zeta do Campus São Bernardo da Universidade Federal do ABC
TITLE:

IMPACT OF NEONATAL TWO-HIT ON IMMUNE CHANGES IN THE BRAIN-GUINT AXIS IN C57BL/6 MICE

PAGES: 76
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUBÁREA: Fisiologia de Órgãos e Sistemas
SPECIALTY: Neurofisiologia
SUMMARY:

The maintenance of proper development occurs at the interface between mother and fetus through a complex balance of physical, hormonal, and immunological changes throughout pregnancy. However, the dynamics of these maternal changes can increase vulnerability to infections, leading to maternal immune activation (MIA), resulting in the high production of cytokines that influence fetal immune response and promote premature birth. Prematurity, in turn, is associated with a range of clinical complications, with neonatal asphyxia being one of the most common, triggering biochemical cascades causing cell death and inflammation in various organs, including the brain and also the intestine, which studies suggest strongly influence neuronal function and play a role in various pathologies. Therefore, our goal was to evaluate the impact of a two-hit model on the brain and intestinal immune response, and its reflection in behavioral changes similar to those observed in individuals with Autism Spectrum Disorder (ASD). Thus, we administered LPS injection on the 14th gestational day (GD14), and after birth, the pups underwent neonatal anoxia for subsequent analysis of cell death and proteins related to the immunology of the medial prefrontal cortex (mPFC) and small intestine in the acute period. Additionally, we assessed the role of Toll-like receptor 4 (TLR4) receptor; for this purpose, two-hit animals were injected with the TAK-242 inhibitor, and somatic and sensorimotor development evaluation was performed until the postnatal age of 21 days (P21). We analyzed their mPFCs and small intestines and possible behavioral changes through the open field and three-chamber tests. We found a reduction in weight in mothers injected with LPS, accompanied by a decrease in litter size. Two-hit animals experienced cell death in the mPFC and increased levels of TLR4 and ARG1 in the analyzed organs during the acute period. We observed a delay in sensorimotor development that was partially attenuated by TAK-242 injection. Furthermore, two-hit animals showed altered social behavior and increased levels of intestinal ARG1 and iNOS. Therefore, this research highlights a modified immune response resulting from a two-hit scenario, in which both the brain and the intestine play a role in disrupting social behavior and modifying the course of postnatal development.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1676367 - ALEXANDRE HIROAKI KIHARA
Membro Titular - Examinador(a) Externo ao Programa - 1771857 - CARLOS ALBERTO DA SILVA
Membro Titular - Examinador(a) Externo ao Programa - 1669152 - DANIEL CARNEIRO CARRETTIERO
Membro Suplente - Examinador(a) Externo à Instituição - GUILHERME SHIGUETO VILAR HIGA - USP
Membro Suplente - Examinador(a) Externo à Instituição - JULIANE MIDORI IKEBARA