Zika virus impairs the development of blood vessels in a mouse model of congenital infection
Autor: | Garcez, P. P., Stolp, H. B., Sravanam, S., Christoff, R. R., Ferreira, J. C. C. G., Dias, A. A., Pezzuto, P., Higa, L. M., Barbeito-Andrés, J., Ferreira, R. O., Andrade, C. B V., Siqueira, M., Santos, T. M. P., Drumond, J., Hoerder-Suabedissen, A., de Lima, C. V. F., Tovar-Moll, F., Lopes, R. T., Fragel-Madeira, L., Lent, R., Ortiga-Carvalho, T. M., Stipursky, J., Bellio, M., Tanuri, A., Molnár, Z. |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Zika Virus Infection
Neurogenesis lcsh:R CEREBRAL CORTEX Brain Endothelial Cells Neovascularization Physiologic lcsh:Medicine Organ Size Zika Virus Embryo Mammalian STORCH Article Mice Inbred C57BL purl.org/becyt/ford/1 [https] Disease Models Animal Animals Blood Vessels Female lcsh:Q lcsh:Science purl.org/becyt/ford/1.6 [https] |
Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Scientific Reports Scientific Reports (Nature) |
Popis: | Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly. Fil: Garcez, P. P.. Universidade Federal do Rio de Janeiro; Brasil Fil: Stolp, H. B.. University of Oxford; Reino Unido Fil: Sravanam, S.. University of Oxford; Reino Unido Fil: Christoff, R. R.. Universidade Federal do Rio de Janeiro; Brasil Fil: Ferreira, J. C. C. G.. Universidade Federal do Rio de Janeiro; Brasil Fil: Dias, A. A.. Universidade Federal do Rio de Janeiro; Brasil Fil: Pezzuto, P.. Universidade Federal do Rio de Janeiro; Brasil Fil: Higa, L. M.. Universidade Federal do Rio de Janeiro; Brasil Fil: Barbeito Andrés, Jimena. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Ferreira, R. O.. Universidade Federal do Rio de Janeiro; Brasil Fil: Andrade, C. B V.. Universidade Federal do Rio de Janeiro; Brasil Fil: Siqueira, M.. Universidade Federal do Rio de Janeiro; Brasil Fil: Santos, T. M. P.. Universidade Federal do Rio de Janeiro; Brasil Fil: Drumond, J.. Universidade Federal do Rio de Janeiro; Brasil Fil: Hoerder Suabedissen, A.. University of Oxford; Reino Unido Fil: de Lima, C. V. F.. Universidade Federal do Rio de Janeiro; Brasil Fil: Tovar Moll, F.. Universidade Federal do Rio de Janeiro; Brasil Fil: Lopes, R. T.. Universidade Federal do Rio de Janeiro; Brasil Fil: Fragel Madeira, L.. Universidade Federal do Rio de Janeiro; Brasil Fil: Lent, R.. Universidade Federal do Rio de Janeiro; Brasil Fil: Ortiga Carvalho, T. M.. Universidade Federal do Rio de Janeiro; Brasil Fil: Stipursky, J.. Universidade Federal do Rio de Janeiro; Brasil Fil: Bellio, M.. Universidade Federal do Rio de Janeiro; Brasil Fil: Tanuri, A.. Universidade Federal do Rio de Janeiro; Brasil Fil: Molnár, Z.. University of Oxford; Reino Unido |
Databáze: | OpenAIRE |
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