Cell adhesion proteins in the cerebrospinal fluid of neonates prenatally exposed to Zika virus: A case–control study

Clara L. Ramos, Eduardo C. Nascimento-Carvalho, Gustavo C. Nascimento-Carvalho, Martijn M. VanDuijn, Ana Luisa Vilas-Boas, Otávio A. Moreno-Carvalho, Lucas P. Carvalho, Lona Zeneyedpour, Gerben Ferwerda, Ronald de Groot, Theo M. Luider, Cristiana M. Nascimento-Carvalho*

*Corresponding author for this work

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To compare cell adhesion molecules levels in cerebrospinal fluid (CSF) between Zika virus (ZIKV)-exposed neonates with/without microcephaly (cases) and controls, 16 neonates (cases), 8 (50%) with and 8 (50%) without microcephaly, who underwent lumbar puncture (LP) during the ZIKV epidemic (2015–2016) were included. All mothers reported ZIKV clinical symptoms during gestation, all neonates presented with congenital infection findings, and other congenital infections were ruled out. Fourteen control neonates underwent LP in the same laboratory (2017–2018). Five cell adhesion proteins were measured in the CSF using mass spectrometry. Neurexin-1 (3.50 [2.00–4.00] vs. 7.5 [5.00–10.25], P = 0.001), neurexin-3 (0.00 [0.00–0.00] vs. 3.00 [1.50–4.00], P = 0.001) and neural cell adhesion molecule 2 (NCAM2) (0.00 [0.00–0.75] vs. 1.00 [1.00–2.00], P = 0.001) were significantly lower in microcephalic and non-microcephalic cases than in controls. When these two sub-groups of prenatally ZIKA-exposed children were compared to controls separately, the same results were found. When cases with and without microcephaly were compared, no difference was found. Neurexin-3 (18.8% vs. 78.6%, P = 0.001) and NCAM2 (25.0% vs. 85.7%, P = 0.001) were less frequently found among the cases. A positive correlation was found between cephalic perimeter and levels of these two proteins. Neurexin-2 and neurexin-2b presented no significant differences. Levels of three cell adhesion proteins were significantly lower in CSF of neonates exposed to ZIKV before birth than in controls, irrespective of presence of congenital microcephaly. Moreover, the smaller the cephalic perimeter, the lower CSF cell adhesion protein levels. These findings suggest that low CSF levels of neurexin-1, neurexin-3 and NCAM2 may reflect the effects of ZIKV on foetal brain development.

Original languageEnglish
Pages (from-to)6258-6268
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number12
Early online date27 Oct 2022
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
This research was sponsored by the Brazilian Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq) (grant number 313466/2018‐1). Clara L. Ramos received research fellowship from the Bahia State Research Support Foundation. Cristiana M. Nascimento‐Carvalho is a senior researcher at the CNPq, Brazil.

Publisher Copyright:
© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.


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