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The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos

The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We u...

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Autores principales: Alsanie, Walaa F., Abdelrahman, Sherin, Alhomrani, Majid, Gaber, Ahmed, Alosimi, Ebtisam Abdulah, Habeeballah, Hamza, Alkhatabi, Heba A., Felimban, Raed I., Hauser, Charlotte A. E., Tayeb, Hossam H., Alamri, Abdulhakeem S., Alamri, Abdulwahab, Raafat, Bassem M., Alswat, Khaled A., Althobaiti, Yusuf S., Asiri, Yousif A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603924/
https://www.ncbi.nlm.nih.gov/pubmed/36293205
http://dx.doi.org/10.3390/ijms232012352
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author Alsanie, Walaa F.
Abdelrahman, Sherin
Alhomrani, Majid
Gaber, Ahmed
Alosimi, Ebtisam Abdulah
Habeeballah, Hamza
Alkhatabi, Heba A.
Felimban, Raed I.
Hauser, Charlotte A. E.
Tayeb, Hossam H.
Alamri, Abdulhakeem S.
Alamri, Abdulwahab
Raafat, Bassem M.
Alswat, Khaled A.
Althobaiti, Yusuf S.
Asiri, Yousif A.
author_facet Alsanie, Walaa F.
Abdelrahman, Sherin
Alhomrani, Majid
Gaber, Ahmed
Alosimi, Ebtisam Abdulah
Habeeballah, Hamza
Alkhatabi, Heba A.
Felimban, Raed I.
Hauser, Charlotte A. E.
Tayeb, Hossam H.
Alamri, Abdulhakeem S.
Alamri, Abdulwahab
Raafat, Bassem M.
Alswat, Khaled A.
Althobaiti, Yusuf S.
Asiri, Yousif A.
author_sort Alsanie, Walaa F.
collection PubMed
description The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase (Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.
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spelling pubmed-96039242022-10-27 The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos Alsanie, Walaa F. Abdelrahman, Sherin Alhomrani, Majid Gaber, Ahmed Alosimi, Ebtisam Abdulah Habeeballah, Hamza Alkhatabi, Heba A. Felimban, Raed I. Hauser, Charlotte A. E. Tayeb, Hossam H. Alamri, Abdulhakeem S. Alamri, Abdulwahab Raafat, Bassem M. Alswat, Khaled A. Althobaiti, Yusuf S. Asiri, Yousif A. Int J Mol Sci Article The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase (Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations. MDPI 2022-10-15 /pmc/articles/PMC9603924/ /pubmed/36293205 http://dx.doi.org/10.3390/ijms232012352 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alsanie, Walaa F.
Abdelrahman, Sherin
Alhomrani, Majid
Gaber, Ahmed
Alosimi, Ebtisam Abdulah
Habeeballah, Hamza
Alkhatabi, Heba A.
Felimban, Raed I.
Hauser, Charlotte A. E.
Tayeb, Hossam H.
Alamri, Abdulhakeem S.
Alamri, Abdulwahab
Raafat, Bassem M.
Alswat, Khaled A.
Althobaiti, Yusuf S.
Asiri, Yousif A.
The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos
title The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos
title_full The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos
title_fullStr The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos
title_full_unstemmed The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos
title_short The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos
title_sort influence of prenatal exposure to quetiapine fumarate on the development of dopaminergic neurons in the ventral midbrain of mouse embryos
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603924/
https://www.ncbi.nlm.nih.gov/pubmed/36293205
http://dx.doi.org/10.3390/ijms232012352
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