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

Walaa F. Alsanie; Sherin Abdelrahman; Raed I. Felimban; Heba A. Alkhatabi; Ahmed Gaber; Ebtisam Abdulah Alosimi; Majid Alhomrani; Hamza Habeeballah; Charlotte 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

doi:10.3390/ijms24065668

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

Walaa F. Alsanie, Sherin Abdelrahman, Raed I. Felimban, Heba A. Alkhatabi, Ahmed Gaber, Ebtisam Abdulah Alosimi, Majid Alhomrani, Hamza Habeeballah, Charlotte 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

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Abstract

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 Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf 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.

Original language	English (US)
Pages (from-to)	5668
Journal	International Journal of Molecular Sciences
Volume	24
Issue number	6
DOIs	https://doi.org/10.3390/ijms24065668
State	Published - Mar 16 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-03-20
Acknowledgements: The research was funded by the Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia, number 1-441-133. Sherin Abdelrahman and Charlotte Hauser thank KAUST for their assistance. The authors would like to thank Christian M. Nefzgar; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. For their invaluable assistance in the central laboratories at Taif University, the authors would like to express their gratitude to Sumaya M. Alghamdi, Talal S. Alzahrani, Sahar Alzahrani, Amjad A. Alshehri, Wasaef A. Aljuaid, Njoud Althibity, Mohammed Matar, Elham A. Althaqafi, and Abdulwahab Alamri.

ASJC Scopus subject areas

Organic Chemistry
Spectroscopy
Molecular Biology
Catalysis
Physical and Theoretical Chemistry
Inorganic Chemistry
Computer Science Applications

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10.3390/ijms24065668

https://repository.kaust.edu.sa/bitstream/10754/690411/1/ijms-24-05668.pdf

Cite this

Alsanie, W. F., Abdelrahman, S., Felimban, R. I., Alkhatabi, H. A., Gaber, A., Alosimi, E. A., Alhomrani, M., Habeeballah, H., Hauser, C., Alamri, A. S., Althobaiti, A., Alsharif, A., Alzahrani, A. S., Al-Ghamdi, M. S., Raafat, B. M., Alswat, K. A., Althobaiti, Y. S., & Asiri, Y. A. (2023). The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain. International Journal of Molecular Sciences, 24(6), 5668. https://doi.org/10.3390/ijms24065668

@article{bec394e3c1534038a7927cc17e055f14,

title = "The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain",

abstract = "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 Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf 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.",

author = "Alsanie, {Walaa F.} and Sherin Abdelrahman and Felimban, {Raed I.} and Alkhatabi, {Heba A.} and Ahmed Gaber and Alosimi, {Ebtisam Abdulah} and Majid Alhomrani and Hamza Habeeballah and Charlotte Hauser and Alamri, {Abdulhakeem S.} and Aiysha Althobaiti and Abdulaziz Alsharif and Alzahrani, {Ahmed S.} and Al-Ghamdi, {Mohammad S.} and Raafat, {Bassem M.} and Alswat, {Khaled A.} and Althobaiti, {Yusuf S.} and Asiri, {Yousif A.}",

note = "KAUST Repository Item: Exported on 2023-03-20 Acknowledgements: The research was funded by the Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia, number 1-441-133. Sherin Abdelrahman and Charlotte Hauser thank KAUST for their assistance. The authors would like to thank Christian M. Nefzgar; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. For their invaluable assistance in the central laboratories at Taif University, the authors would like to express their gratitude to Sumaya M. Alghamdi, Talal S. Alzahrani, Sahar Alzahrani, Amjad A. Alshehri, Wasaef A. Aljuaid, Njoud Althibity, Mohammed Matar, Elham A. Althaqafi, and Abdulwahab Alamri.",

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month = mar,

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Alsanie, WF, Abdelrahman, S, Felimban, RI, Alkhatabi, HA, Gaber, A, Alosimi, EA, Alhomrani, M, Habeeballah, H, Hauser, C, Alamri, AS, Althobaiti, A, Alsharif, A, Alzahrani, AS, Al-Ghamdi, MS, Raafat, BM, Alswat, KA, Althobaiti, YS & Asiri, YA 2023, 'The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain', International Journal of Molecular Sciences, vol. 24, no. 6, pp. 5668. https://doi.org/10.3390/ijms24065668

TY - JOUR

T1 - The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain

AU - Alsanie, Walaa F.

AU - Abdelrahman, Sherin

AU - Felimban, Raed I.

AU - Alkhatabi, Heba A.

AU - Gaber, Ahmed

AU - Alosimi, Ebtisam Abdulah

AU - Alhomrani, Majid

AU - Habeeballah, Hamza

AU - Hauser, Charlotte

AU - Alamri, Abdulhakeem S.

AU - Althobaiti, Aiysha

AU - Alsharif, Abdulaziz

AU - Alzahrani, Ahmed S.

AU - Al-Ghamdi, Mohammad S.

AU - Raafat, Bassem M.

AU - Alswat, Khaled A.

AU - Althobaiti, Yusuf S.

AU - Asiri, Yousif A.

N1 - KAUST Repository Item: Exported on 2023-03-20 Acknowledgements: The research was funded by the Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia, number 1-441-133. Sherin Abdelrahman and Charlotte Hauser thank KAUST for their assistance. The authors would like to thank Christian M. Nefzgar; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. For their invaluable assistance in the central laboratories at Taif University, the authors would like to express their gratitude to Sumaya M. Alghamdi, Talal S. Alzahrani, Sahar Alzahrani, Amjad A. Alshehri, Wasaef A. Aljuaid, Njoud Althibity, Mohammed Matar, Elham A. Althaqafi, and Abdulwahab Alamri.

PY - 2023/3/16

Y1 - 2023/3/16

N2 - 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 Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf 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.

AB - 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 Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf 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.

UR - http://hdl.handle.net/10754/690411

UR - https://www.mdpi.com/1422-0067/24/6/5668

U2 - 10.3390/ijms24065668

DO - 10.3390/ijms24065668

M3 - Article

C2 - 36982742

SN - 1661-6596

VL - 24

SP - 5668

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 6

ER -

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

Abstract

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