TY - JOUR
T1 - Prenatal Exposure to Gabapentin Alters the Development of Ventral Midbrain Dopaminergic Neurons
AU - Alsanie, Walaa F
AU - Abdelrahman, Sherin
AU - Alhomrani, Majid
AU - Gaber, Ahmed
AU - Habeeballah, Hamza
AU - Alkhatabi, Heba A
AU - Felimban, Raed I
AU - Hauser, Charlotte
AU - Tayeb, Hossam H
AU - Alamri, Abdulhakeem S
AU - Raafat, Bassem M
AU - Anwar, Sirajudheen
AU - Alswat, Khaled A
AU - Althobaiti, Yusuf S
AU - Asiri, Yousif A
N1 - KAUST Repository Item: Exported on 2022-09-14
Acknowledgements: The present research received fund from the Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia, through project number 1-441-133. The authors are appreciatively to Dr. Christian M. Nefzgar; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia, and to Dr. Abdulwahab Alamri; College of Pharmacy, University of Hail, Saudi Arabia for their technical support. Charlotte A. E. Hauser and Sherin Abdelrahman would like to thank kaust for their support. Also, authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia, for funding this work through project number 1-441-133.
PY - 2022/7/22
Y1 - 2022/7/22
N2 - Background: Gabapentin is widely prescribed as an off-label drug for the treatment of various diseases, including drug and alcohol addiction. Approximately 83–95% of the usage of gabapentin is off-label, accounting for more than 90% of its sales in the market, which indicates an alarming situation of drug abuse. Such misuse of gabapentin has serious negative consequences. The safety of the use of gabapentin in pregnant women has always been a serious issue, as gabapentin can cross placental barriers. The impact of gabapentin on brain development in the fetus is not sufficiently investigated, which poses difficulties in clinical decisions regarding prescriptions.
Methods: The consequences effect of prenatal gabapentin exposure on the development of ventral midbrain dopaminergic neurons were investigated using three-dimensional neuronal cell cultures. Time-mated Swiss mice were used to isolate embryos. The ventral third of the midbrain was removed and used to enrich the dopaminergic population in 3D cell cultures that were subsequently exposed to gabapentin. The effects of gabapentin on the viability, ATP release, morphogenesis and genes expression of ventral midbrain dopaminergic neurons were investigated.
Results: Gabapentin treatment at the therapeutic level interfered with the neurogenesis and morphogenesis of vmDA neurons in the fetal brain by causing changes in morphology and alterations in the expression of key developmental genes, such as Nurr1, Chl1, En1, Bdnf, Drd2, and Pitx3. The TH + total neurite length and dominant neurite length were significantly altered. We also found that gabapentin could halt the metabolic state of these neuronal cells by blocking the generation of ATP.
Conclusion: Our findings clearly indicate that gabapentin hampers the morphogenesis and development of dopaminergic neurons. This implies that the use of gabapentin could lead to serious complications in child-bearing women. Therefore, caution must be exercised in clinical decisions regarding the prescription of gabapentin in pregnant women.
AB - Background: Gabapentin is widely prescribed as an off-label drug for the treatment of various diseases, including drug and alcohol addiction. Approximately 83–95% of the usage of gabapentin is off-label, accounting for more than 90% of its sales in the market, which indicates an alarming situation of drug abuse. Such misuse of gabapentin has serious negative consequences. The safety of the use of gabapentin in pregnant women has always been a serious issue, as gabapentin can cross placental barriers. The impact of gabapentin on brain development in the fetus is not sufficiently investigated, which poses difficulties in clinical decisions regarding prescriptions.
Methods: The consequences effect of prenatal gabapentin exposure on the development of ventral midbrain dopaminergic neurons were investigated using three-dimensional neuronal cell cultures. Time-mated Swiss mice were used to isolate embryos. The ventral third of the midbrain was removed and used to enrich the dopaminergic population in 3D cell cultures that were subsequently exposed to gabapentin. The effects of gabapentin on the viability, ATP release, morphogenesis and genes expression of ventral midbrain dopaminergic neurons were investigated.
Results: Gabapentin treatment at the therapeutic level interfered with the neurogenesis and morphogenesis of vmDA neurons in the fetal brain by causing changes in morphology and alterations in the expression of key developmental genes, such as Nurr1, Chl1, En1, Bdnf, Drd2, and Pitx3. The TH + total neurite length and dominant neurite length were significantly altered. We also found that gabapentin could halt the metabolic state of these neuronal cells by blocking the generation of ATP.
Conclusion: Our findings clearly indicate that gabapentin hampers the morphogenesis and development of dopaminergic neurons. This implies that the use of gabapentin could lead to serious complications in child-bearing women. Therefore, caution must be exercised in clinical decisions regarding the prescription of gabapentin in pregnant women.
UR - http://hdl.handle.net/10754/680236
UR - https://www.frontiersin.org/articles/10.3389/fphar.2022.923113/full
U2 - 10.3389/fphar.2022.923113
DO - 10.3389/fphar.2022.923113
M3 - Article
C2 - 35942222
SN - 1663-9812
VL - 13
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
ER -
