The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons
Walaa F. Alsanie,
Majid Alhomrani,
Ahmed Gaber,
Hamza Habeeballah,
Heba A. Alkhatabi,
Raed I. Felimban,
Sherin Abdelrahman,
Charlotte A. E. Hauser,
Adeel G. Chaudhary,
Abdulhakeem S. Alamri,
Bassem M. Raafat,
Abdulwahab Alamri,
Sirajudheen Anwar,
Khaled A. Alswat,
Yusuf S. Althobaiti,
Yousif A. Asiri
Affiliations
Walaa F. Alsanie
Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Majid Alhomrani
Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Ahmed Gaber
Centre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Hamza Habeeballah
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences in Rabigh, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Heba A. Alkhatabi
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Raed I. Felimban
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Sherin Abdelrahman
Laboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia
Charlotte A. E. Hauser
Laboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia
Adeel G. Chaudhary
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Abdulhakeem S. Alamri
Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Bassem M. Raafat
Department of Radiological Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Abdulwahab Alamri
Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 55211, Saudi Arabia
Sirajudheen Anwar
Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 55211, Saudi Arabia
Khaled A. Alswat
Department of Internal Medicine, School of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Yusuf S. Althobaiti
Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Yousif A. Asiri
Department of Clinical Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Pregabalin is widely used as a treatment for multiple neurological disorders; however, it has been reported to have the potential for misuse. Due to a lack of safety studies in pregnancy, pregabalin is considered the last treatment option for various neurological diseases, such as neuropathic pain. Therefore, pregabalin abuse in pregnant women, even at therapeutic doses, may impair fetal development. We used primary mouse embryonic neurons to investigate whether exposure to pregabalin can impair the morphogenesis and differentiation of ventral midbrain neurons. This study focused on ventral midbrain dopaminergic neurons, as they are responsible for cognition, movement, and behavior. The results showed that pregabalin exposure during early brain development induced upregulation of the dopaminergic progenitor genes Lmx1a and Nurr1 and the mature dopaminergic gene Pitx3. Interestingly, pregabalin had different effects on the morphogenesis of non-dopaminergic ventral midbrain neurons. Importantly, our findings illustrated that a therapeutic dose of pregabalin (10 μM) did not affect the viability of neurons. However, it caused a decrease in ATP release in ventral midbrain neurons. We demonstrated that exposure to pregabalin during early brain development could interfere with the neurogenesis and morphogenesis of ventral midbrain dopaminergic neurons. These findings are crucial for clinical consideration of the use of pregabalin during pregnancy.
