The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morpho...

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Main Authors: Walaa F. Alsanie, Sherin Abdelrahman, Raed I. Felimban, Heba A. Alkhatabi, Ahmed Gaber, Ebtisam Abdulah Alosimi, Majid Alhomrani, Hamza Habeeballah, Charlotte A. E. Hauser, Abdulhakeem S. Alamri, Aiysha Althobaiti, Abdulaziz Alsharif, Ahmed S. Alzahrani, Mohammad S. Al-Ghamdi, Bassem M. Raafat, Khaled A. Alswat, Yusuf S. Althobaiti, Yousif A. Asiri
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/6/5668
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author Walaa F. Alsanie
Sherin Abdelrahman
Raed I. Felimban
Heba A. Alkhatabi
Ahmed Gaber
Ebtisam Abdulah Alosimi
Majid Alhomrani
Hamza Habeeballah
Charlotte A. E. Hauser
Abdulhakeem S. Alamri
Aiysha Althobaiti
Abdulaziz Alsharif
Ahmed S. Alzahrani
Mohammad S. Al-Ghamdi
Bassem M. Raafat
Khaled A. Alswat
Yusuf S. Althobaiti
Yousif A. Asiri
author_facet Walaa F. Alsanie
Sherin Abdelrahman
Raed I. Felimban
Heba A. Alkhatabi
Ahmed Gaber
Ebtisam Abdulah Alosimi
Majid Alhomrani
Hamza Habeeballah
Charlotte A. E. Hauser
Abdulhakeem S. Alamri
Aiysha Althobaiti
Abdulaziz Alsharif
Ahmed S. Alzahrani
Mohammad S. Al-Ghamdi
Bassem M. Raafat
Khaled A. Alswat
Yusuf S. Althobaiti
Yousif A. Asiri
author_sort Walaa F. Alsanie
collection DOAJ
description Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated <i>Lmx1a</i>, <i>En1</i>, <i>Pitx3</i>, <i>Th</i>, <i>Chl1</i>, <i>Dat</i>, and <i>Drd1</i> but did not affect <i>Nurr1</i> or <i>Bdnf</i> expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.
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spelling doaj.art-f76f07a47a1b49b28575ad7e2a94e9b52023-11-17T11:37:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246566810.3390/ijms24065668The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral MidbrainWalaa F. Alsanie0Sherin Abdelrahman1Raed I. Felimban2Heba A. Alkhatabi3Ahmed Gaber4Ebtisam Abdulah Alosimi5Majid Alhomrani6Hamza Habeeballah7Charlotte A. E. Hauser8Abdulhakeem S. Alamri9Aiysha Althobaiti10Abdulaziz Alsharif11Ahmed S. Alzahrani12Mohammad S. Al-Ghamdi13Bassem M. Raafat14Khaled A. Alswat15Yusuf S. Althobaiti16Yousif A. Asiri17Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaLaboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaCentre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, Taif 21944, Saudi ArabiaCentre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, Taif 21944, Saudi ArabiaDepartment of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences in Rabigh, King Abdulaziz University, Jeddah 21589, Saudi ArabiaLaboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi ArabiaDepartment of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaCentre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, Taif 21944, Saudi ArabiaDepartment of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaCentre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, Taif 21944, Saudi ArabiaDepartment of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Radiological Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Internal Medicine, School of Medicine, Taif University, Taif 21944, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif 21944, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, Taif University, Taif 21944, Saudi ArabiaMethamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated <i>Lmx1a</i>, <i>En1</i>, <i>Pitx3</i>, <i>Th</i>, <i>Chl1</i>, <i>Dat</i>, and <i>Drd1</i> but did not affect <i>Nurr1</i> or <i>Bdnf</i> expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.https://www.mdpi.com/1422-0067/24/6/5668methamphetaminedopaminergic neuronsfetal neurodevelopmentventral midbrainembryonic neurons
spellingShingle Walaa F. Alsanie
Sherin Abdelrahman
Raed I. Felimban
Heba A. Alkhatabi
Ahmed Gaber
Ebtisam Abdulah Alosimi
Majid Alhomrani
Hamza Habeeballah
Charlotte A. E. Hauser
Abdulhakeem S. Alamri
Aiysha Althobaiti
Abdulaziz Alsharif
Ahmed S. Alzahrani
Mohammad S. Al-Ghamdi
Bassem M. Raafat
Khaled A. Alswat
Yusuf S. Althobaiti
Yousif A. Asiri
The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain
International Journal of Molecular Sciences
methamphetamine
dopaminergic neurons
fetal neurodevelopment
ventral midbrain
embryonic neurons
title The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain
title_full The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain
title_fullStr The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain
title_full_unstemmed The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain
title_short The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain
title_sort influence of prenatal exposure to methamphetamine on the development of dopaminergic neurons in the ventral midbrain
topic methamphetamine
dopaminergic neurons
fetal neurodevelopment
ventral midbrain
embryonic neurons
url https://www.mdpi.com/1422-0067/24/6/5668
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