Banca de DEFESA: EMANUELLY KARINE CAMPOS CHAVES

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : EMANUELLY KARINE CAMPOS CHAVES
DATE: 27/04/2026
TIME: 13:30
LOCAL: https://meet.google.com/uim-kvuk-kjp e Auditorio do Instituto do Cerebro
TITLE:

Study of the relationship between the development of the glymphatic system and the window of susceptibility of the nervous system to Zika virus infection

KEY WORDS:

microcephaly; teratogenesis;congenit al Zika virus syndrome;  arboviruses; embryo;

PAGES: 56
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:

In all body tissues, lymphatic drainage contributes to innate immunity. In the central nervous system, fluid drainage from the parenchyma is carried out by the glymphatic system. Maturation of the glymphatic system marks the beginning of fluid dynamics in the central nervous system (CNS). In this study, we demonstrate that the onset of fluid drainage is associated with a significant reduction in CNS susceptibility to Zika virus (ZIKV) infection. In mice, ZIKV inoculation before complete development of the glymphatic system (GS) results in extensive viral infection, accompanied by vascular deformities and disorganization of aquaporin 4 (Aqp4)-expressing astrocytic networks. In contrast, after the formation and maturation of the glymphatic system, exposure to the same viral challenge is unable to induce clinical disease or establish persistent infection in brain tissue. The observation of a temporal correlation between the development of the GS and the decrease in susceptibility to ZIKV led us to test whether GS inhibition could reopen the window. An important component of cerebrospinal fluid movement into vessels formed by astrocytes is the contractility of the meningeal arteries. Thus, we chose the drug SR-49059, a vasopressin 1a receptor antagonist, which reduces arterial contraction. We injected ZIKV into the brains of P14 mice, an age at which controls exhibit reduced susceptibility, along with SR-49059 or the vehicle solution. Our results show that treatment with SR-49059 leaves P14 mice susceptible to ZIKV-induced disease following intracerebral injection. Furthermore, their brains exhibit alterations in blood vessel caliber and permeability of protein solutes between cerebrospinal fluid and parenchyma, observations similar to those found in infected neonates. These results highlight the SG as a fundamental mechanism for draining parenchymal particles, including viral particles. Our bioinformatics findings indicate that the onset of Aqp4 expression by the human SG occurs in the third trimester. Therefore, our experimental findings offer a possible explanation for the lower susceptibility of human fetuses in late stages of gestation and newborns to ZIKV infection.

COMMITTEE MEMBERS:
Presidente - 2394627 - EDUARDO BOUTH SEQUERRA
Externo à Instituição - LEO MORITA MIYAKOSHI - IP
Externo à Instituição - THIAGO MATTAR CUNHA - USP