Cargando…
Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model
Efavirenz is recommended as a preferred first-line drug for women of childbearing potential living with human immunodeficiency virus. Efavirenz is known for its central nervous system side effects, which are partly mediated by serotonergic actions. The neurotransmitter serotonin exerts neurotrophic...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370772/ https://www.ncbi.nlm.nih.gov/pubmed/30745561 http://dx.doi.org/10.1038/s41398-019-0420-y |
_version_ | 1783394419851919360 |
---|---|
author | van de Wijer, Lisa Garcia, Lidiane P. Hanswijk, Sabrina I. Rando, Juliette Middelman, Anthonieke ter Heine, Rob Mast, Quirijn de Martens, Gerard J. M. van der Ven, André J. A. M. Kolk, Sharon M. Schellekens, Arnt F. A. Homberg, Judith R. |
author_facet | van de Wijer, Lisa Garcia, Lidiane P. Hanswijk, Sabrina I. Rando, Juliette Middelman, Anthonieke ter Heine, Rob Mast, Quirijn de Martens, Gerard J. M. van der Ven, André J. A. M. Kolk, Sharon M. Schellekens, Arnt F. A. Homberg, Judith R. |
author_sort | van de Wijer, Lisa |
collection | PubMed |
description | Efavirenz is recommended as a preferred first-line drug for women of childbearing potential living with human immunodeficiency virus. Efavirenz is known for its central nervous system side effects, which are partly mediated by serotonergic actions. The neurotransmitter serotonin exerts neurotrophic effects during neurodevelopment and antenatal exposure to serotonergic agents has been linked to developmental delay. Although the teratogenic risks of efavirenz appear to be minimal, data on long-term developmental effects remain scarce. Here, we aimed to investigate the short- and long-term behavioral and neurodevelopmental effects of perinatal efavirenz exposure. We treated pregnant rats from gestation day 1 until postnatal day 7 with efavirenz (100 mg/kg) or vehicle. We measured behavioral outcomes in male offspring during the first 3 postnatal weeks, adolescence and adulthood, and conducted brain immunohistochemistry analyses after sacrifice. Perinatal efavirenz exposure resulted in reduced body weight and delayed reflex and motor development. During adulthood, we observed a decrease in the total number of cells and mature neurons in the motor cortex, as well as an increase in the number of Caspase-3-positive cells and serotonergic fibers. Together, our data show a developmental delay and persistent changes in the brain motor cortex of rats exposed to efavirenz perinatally. Because over 1 million children born annually are exposed to antiretroviral therapy, our findings underline the need for clinical studies on long-term neurodevelopmental outcomes of perinatal exposure to efavirenz. |
format | Online Article Text |
id | pubmed-6370772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63707722019-02-15 Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model van de Wijer, Lisa Garcia, Lidiane P. Hanswijk, Sabrina I. Rando, Juliette Middelman, Anthonieke ter Heine, Rob Mast, Quirijn de Martens, Gerard J. M. van der Ven, André J. A. M. Kolk, Sharon M. Schellekens, Arnt F. A. Homberg, Judith R. Transl Psychiatry Article Efavirenz is recommended as a preferred first-line drug for women of childbearing potential living with human immunodeficiency virus. Efavirenz is known for its central nervous system side effects, which are partly mediated by serotonergic actions. The neurotransmitter serotonin exerts neurotrophic effects during neurodevelopment and antenatal exposure to serotonergic agents has been linked to developmental delay. Although the teratogenic risks of efavirenz appear to be minimal, data on long-term developmental effects remain scarce. Here, we aimed to investigate the short- and long-term behavioral and neurodevelopmental effects of perinatal efavirenz exposure. We treated pregnant rats from gestation day 1 until postnatal day 7 with efavirenz (100 mg/kg) or vehicle. We measured behavioral outcomes in male offspring during the first 3 postnatal weeks, adolescence and adulthood, and conducted brain immunohistochemistry analyses after sacrifice. Perinatal efavirenz exposure resulted in reduced body weight and delayed reflex and motor development. During adulthood, we observed a decrease in the total number of cells and mature neurons in the motor cortex, as well as an increase in the number of Caspase-3-positive cells and serotonergic fibers. Together, our data show a developmental delay and persistent changes in the brain motor cortex of rats exposed to efavirenz perinatally. Because over 1 million children born annually are exposed to antiretroviral therapy, our findings underline the need for clinical studies on long-term neurodevelopmental outcomes of perinatal exposure to efavirenz. Nature Publishing Group UK 2019-02-11 /pmc/articles/PMC6370772/ /pubmed/30745561 http://dx.doi.org/10.1038/s41398-019-0420-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article van de Wijer, Lisa Garcia, Lidiane P. Hanswijk, Sabrina I. Rando, Juliette Middelman, Anthonieke ter Heine, Rob Mast, Quirijn de Martens, Gerard J. M. van der Ven, André J. A. M. Kolk, Sharon M. Schellekens, Arnt F. A. Homberg, Judith R. Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model |
title | Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model |
title_full | Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model |
title_fullStr | Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model |
title_full_unstemmed | Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model |
title_short | Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model |
title_sort | neurodevelopmental and behavioral consequences of perinatal exposure to the hiv drug efavirenz in a rodent model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370772/ https://www.ncbi.nlm.nih.gov/pubmed/30745561 http://dx.doi.org/10.1038/s41398-019-0420-y |
work_keys_str_mv | AT vandewijerlisa neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT garcialidianep neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT hanswijksabrinai neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT randojuliette neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT middelmananthonieke neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT terheinerob neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT mastquirijnde neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT martensgerardjm neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT vandervenandrejam neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT kolksharonm neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT schellekensarntfa neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel AT hombergjudithr neurodevelopmentalandbehavioralconsequencesofperinatalexposuretothehivdrugefavirenzinarodentmodel |