Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Centre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Cells. 2022 Mar 1;11(5):852. doi: 10.3390/cells11050852.
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 and and the mature dopaminergic gene . 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.
普瑞巴林被广泛用作治疗多种神经紊乱的药物；然而，据报道它有被滥用的可能。由于缺乏对妊娠安全性的研究，普瑞巴林被认为是治疗各种神经疾病的最后选择，如神经性疼痛。因此，孕妇即使在治疗剂量下滥用普瑞巴林，也可能损害胎儿发育。我们使用原代小鼠胚胎神经元来研究普瑞巴林暴露是否会损害腹侧中脑神经元的形态发生和分化。本研究集中于腹侧中脑多巴胺能神经元，因为它们负责认知、运动和行为。结果表明，早期大脑发育过程中普瑞巴林暴露会诱导多巴胺能祖细胞基因 和 以及成熟多巴胺能基因 的上调。有趣的是，普瑞巴林对非多巴胺能腹侧中脑神经元的形态发生有不同的影响。重要的是，我们的研究结果表明，治疗剂量的普瑞巴林（10 μM）不会影响神经元的活力。然而，它会导致腹侧中脑神经元中 ATP 释放减少。我们证明，早期大脑发育过程中普瑞巴林的暴露可能会干扰腹侧中脑多巴胺能神经元的神经发生和形态发生。这些发现对于临床考虑在怀孕期间使用普瑞巴林至关重要。
