Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

被引：23

作者：

Stanelle-Bertram, Stephanie ^{[1
]}

Walendy-Gnirss, Kerstin ^{[1
]}

Speiseder, Thomas ^{[1
]}

Thiele, Swantje ^{[1
]}

Asante, Ivy Asantewaa ^{[1
]}

Dreier, Carola ^{[1
]}

Kouassi, Nancy Mounogou ^{[1
]}

Preuss, Annette ^{[1
]}

Pilnitz-Stolze, Gundula ^{[1
]}

Mueller, Ursula ^{[1
]}

Thanisch, Stefanie ^{[1
]}

Richter, Melanie ^{[2
]}

Scharrenberg, Robin ^{[2
]}

Kraus, Vanessa ^{[3
]}

Doerk, Ronja ^{[3
]}

Schau, Lynn ^{[3
]}

Herder, Vanessa ^{[4
,5
]}

Gerhauser, Ingo ^{[4
]}

Pfankuche, Vanessa Maria ^{[4
,5
]}

Kaeufer, Christopher ^{[6
]}

Waltl, Inken ^{[6
]}

Moraes, Thais ^{[7
]}

Sellau, Julie ^{[8
]}

Hoenow, Stefan ^{[8
]}

Schmidt-Chanasit, Jonas ^{[8
,9
]}

Jansen, Stephanie ^{[8
]}

Schattling, Benjamin ^{[10
]}

Ittrich, Harald ^{[11
]}

Bartsch, Udo ^{[12
]}

Renne, Thomas ^{[13
]}

Bartenschlager, Ralf ^{[7
]}

Arck, Petra ^{[14
]}

Cadar, Daniel ^{[8
]}

Friese, Manuel A. ^{[10
]}

Vapalahti, Olli ^{[15
,16
]}

Lotter, Hanna ^{[8
]}

Benites, Sany ^{[17
]}

Rolling, Lane ^{[17
]}

Gabriel, Martin ^{[8
]}

Baumgaertner, Wolfgang ^{[4
,5
]}

Morellini, Fabio ^{[3
]}

Hoelter, Sabine M. ^{[18
,19
]}

Amarie, Oana ^{[18
,19
]}

Fuchs, Helmut ^{[19
]}

de Angelis, Martin Hrabe ^{[19
,20
,21
]}

Loescher, Wolfgang ^{[6
]}

de Anda, Froylan Calderon ^{[2
]}

Gabriel, Guelsah ^{[1
,9
,22
,23
]}

机构：

[1] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Ctr Mol Neurobiol Hamburg ZNMH, Neuronal Dev, Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Ctr Mol Neurobiol Hamburg ZNMH, Res Grp Behav Biol, Hamburg, Germany

[4] Univ Vet Med, Dept Pathol, Hannover, Germany

[5] Ctr Syst Neurosci, Hannover, Germany

[6] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Hannover, Germany

[7] Heidelberg Univ, Dept Infect Dis, Mol Virol, Heidelberg, Germany

[8] Bernhard Nocht Inst Trop Med, Hamburg, Germany

[9] German Ctr Infect Res DZIF, Partner Site Hamburg Lubeck Borstel Riems, Hamburg, Germany

[10] Univ Med Ctr Hamburg Eppendorf, Inst Neuroimmunol & Multiple Sclerosis, Hamburg, Germany

[11] Univ Med Ctr Hamburg Eppendorf, Dept Diagnost & Intervent Radiol & Nucl Med, Hamburg, Germany

[12] Univ Med Ctr Hamburg Eppendorf, Dept Ophthalmol, Hamburg, Germany

[13] Univ Med Ctr Hamburg Eppendorf, Inst Clin & Lab Chem, Hamburg, Germany

[14] Univ Med Ctr Hamburg Eppendorf, Dept Obstet & Fetal Med, Hamburg, Germany

[15] Univ Helsinki, Helsinki, Finland

[16] Helsinki Univ Hosp, Helsinki, Finland

[17] Trop Pathol & Infect Dis Assoc, Cuzco, Peru

[18] Helmholtz Zentrum Munchen, Inst Dev Genet, Neuherberg, Germany

[19] Helmholtz Zentrum Munchen, Inst Expt Genet, German Mouse Clin, Neuherberg, Germany

[20] Tech Univ Munich, Sch Life Sci Weihenstephan, Chair Expt Genet, Freising Weihenstephan, Germany

[21] German Ctr Diabet Res DZD, Neuherberg, Germany

[22] Univ Lubeck, Ctr Struct & Cell Biol Med, Lubeck, Germany

[23] Univ Vet Med, Hannover, Germany

来源：

NATURE MICROBIOLOGY | 2018年 / 3卷 / 10期

关键词：

MORRIS WATER MAZE; VIRUS; TESTOSTERONE; BRAIN; PREGNANCY; LEADS; EXPOSURE; GROWTH;

D O I：

10.1038/s41564-018-0236-1

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：1161 / +

页数：17

共 3 条

[1] Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood
Stephanie Stanelle-Bertram
Kerstin Walendy-Gnirß
Thomas Speiseder
Swantje Thiele
Ivy Asantewaa Asante
Carola Dreier
Nancy Mounogou Kouassi
Annette Preuß
Gundula Pilnitz-Stolze
Ursula Müller
Stefanie Thanisch
Melanie Richter
Robin Scharrenberg
Vanessa Kraus
Ronja Dörk
Lynn Schau
Vanessa Herder
Ingo Gerhauser
Vanessa Maria Pfankuche
Christopher Käufer
Inken Waltl
Thais Moraes
Julie Sellau
Stefan Hoenow
Jonas Schmidt-Chanasit
Stephanie Jansen
Benjamin Schattling
Harald Ittrich
Udo Bartsch
Thomas Renné
Ralf Bartenschlager
Petra Arck
Daniel Cadar
Manuel A. Friese
Olli Vapalahti
Hanna Lotter
Sany Benites
Lane Rolling
Martin Gabriel
Wolfgang Baumgärtner
Fabio Morellini
Sabine M. Hölter
Oana Amarie
Helmut Fuchs
Martin Hrabe de Angelis
Wolfgang Löscher
Froylan Calderon de Anda
Gülsah Gabriel
Nature Microbiology, 2018, 3 : 1161 - 1174
[2] The influence of childhood aspirations on the risk of developing psychotic disorders, substance use disorders, and dual diagnosis in adulthood based on the Metropolit 1953 Danish Male Birth Cohort
Kyster, Natacha Blauenfeldt
Tranberg, Katrine
Osler, Merete
Hjorthoj, Carsten
Martensson, Solvej
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY, 2023, 32 (12) : 2503 - 2512
[3] The influence of childhood aspirations on the risk of developing psychotic disorders, substance use disorders, and dual diagnosis in adulthood based on the Metropolit 1953 Danish Male Birth Cohort
Natacha Blauenfeldt Kyster
Katrine Tranberg
Merete Osler
Carsten Hjorthøj
Solvej Mårtensson
European Child & Adolescent Psychiatry, 2023, 32 : 2503 - 2512

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