1. Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood
- Author
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Christopher Käufer, Julie Sellau, Fabio Morellini, Stephanie Jansen, Ralf Bartenschlager, Ursula Müller, Melanie Richter, Lynn Schau, Robin Scharrenberg, Annette Preuß, Jonas Schmidt-Chanasit, Wolfgang Löscher, Stephanie Stanelle-Bertram, Helmut Fuchs, Sabine M. Hölter, Petra C. Arck, Oana V. Amarie, Vanessa Herder, Gülsah Gabriel, Vanessa M. Pfankuche, Carola Dreier, Froylan Calderon de Anda, Hanna Lotter, Ingo Gerhauser, Vanessa Kraus, Kerstin Walendy-Gnirß, Ronja Dörk, Gundula Pilnitz-Stolze, Olli Vapalahti, Martin Gabriel, Thais Moraes, Sany Benites, Stefan Hoenow, Daniel Cadar, Harald Ittrich, Benjamin Schattling, Swantje Thiele, Lane Rolling, Ivy Asantewaa Asante, Udo Bartsch, Stefanie Thanisch, Manuel A. Friese, Inken Waltl, Thomas Speiseder, Martin Hrabé de Angelis, Thomas Renné, Nancy Mounogou Kouassi, Wolfgang Baumgärtner, Medicum, Veterinary Microbiology and Epidemiology, Veterinary Biosciences, Olli Pekka Vapalahti / Principal Investigator, Viral Zoonosis Research Unit, Department of Virology, University of Helsinki, and Clinicum
- Subjects
Male ,0301 basic medicine ,Physiology ,Morris water navigation task ,Applied Microbiology and Biotechnology ,Zika virus ,Pregnancy ,Testosterone ,Pregnancy Complications, Infectious ,biology ,Learning Disabilities ,Zika Virus Infection ,Brain ,3. Good health ,MORRIS WATER MAZE ,LEADS ,In utero ,GROWTH ,Female ,Microbiology (medical) ,Offspring ,Birth weight ,MODELS ,Immunology ,Neurocognitive Disorders ,VIRUS-INFECTION ,Microbiology ,03 medical and health sciences ,Sex Factors ,Genetics ,medicine ,Animals ,Humans ,EXPOSURE ,Fetus ,business.industry ,MEMORY ,Zika Virus ,Cell Biology ,Placental Insufficiency ,biology.organism_classification ,medicine.disease ,Infectious Disease Transmission, Vertical ,Disease Models, Animal ,030104 developmental biology ,Animals, Newborn ,3111 Biomedicine ,business ,Neurocognitive - Abstract
Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in -1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.
- Published
- 2018