Dados do Trabalho

Título

Zika virus-antibody complex damage risk: in vitro analysis in neural progenitor cells of newborn rats

Introdução

Zika virus (ZIKV), in the last years, has been associated with central nervous system damage, such as microcephaly; yet little is known about the action mechanisms and the pathophysiology of this condition. In this context, aggregated neural progenitors, called neurospheres, can contribute to the investigation of the mechanisms involved in brain malformation pathologies. Neurospheres are conglomerates of neural stem cells and progenitor cells used as an in vitro model for the embryonic neurogenesis study, generating a similar environment to brain formation.

Objetivo

The aim of the present study is to evaluate the harmful or immunizing effects of anti-IgG antibodies for ZIKV against virus re-exposure during different stages of brain neoformation.

Método

The morphology of neurospheres supplemented with serum from IgG+ pregnant women exposed to ZIKV was evaluated for its shape irregularity using the Image ProPlus 7 software. The expression analysis of the NOTCH-1 gene was performed during the neurospheres development by using the qRT-PCR technique, since this gene is involved in processes related to cell specification, differentiation, proliferation and survival, and its regular expression is essential for nerve cell development.

Resultados

The IgG+ serum for ZIKV seems to proffer a protective potential on the cells, providing a significantly decrease in the cellular irregularity of the neurospheres when exposed to a lower concentration of virus. The ZIKV exposure sharply increased NOTCH-1 expression immediately and at 72 hours post-infection, at the highest virus concentration. On the other hand, IgG+ serum for ZIKV presented a significant protective effect on cells that were later exposed to the virus, keeping NOTCH-1 levels similar to the control group. The remarkable increased in the NOTCH-1 expression due to ZIKV exposure can be interpreted in different ways. Considering that ZIKV interferes in the maintenance and the proliferation of stem cells, it is likely that the virus is altering developmental-related genes, such as NOTCH-1, damaging cell development. Besides, it could be possible that, under the influence of ZIKV, the neurospheres triggered a premature differentiation process, increasing the NOTCH-1 expression levels, which would probably lead to cell depletion.

Conclusão

Previous exposure to IgG+ serum for ZIKV appears to protectively interfere in neurospheres exposed to ZIKV strains regarding their irregularity and expression of NOTCH-1 gene.

Palavras-chave

Neurospheres, Neurodevelopment, ZIKV

Área

Neurociência básica