Alsanie Walaa F, Abdelrahman Sherin, Alhomrani Majid, Gaber Ahmed, Habeeballah Hamza, Alkhatabi Heba A, Felimban Raed I, Hauser Charlotte A E, Tayeb Hossam H, Alamri Abdulhakeem S, Raafat Bassem M, Anwar Sirajudheen, Alswat Khaled A, Althobaiti Yusuf S, Asiri Yousif A
Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
Centre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, Taif, Saudi Arabia.
Front Pharmacol. 2022 Jul 22;13:923113. doi: 10.3389/fphar.2022.923113. eCollection 2022.
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. 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. 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 and 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. 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.
加巴喷丁作为一种治疗包括药物和酒精成瘾在内的各种疾病的非标签药物被广泛处方。加巴喷丁约83 - 95%的使用属于非标签用药，占其市场销售额的90%以上，这表明了药物滥用的惊人状况。加巴喷丁的这种滥用有严重的负面后果。加巴喷丁在孕妇中使用的安全性一直是一个严重问题，因为加巴喷丁可以穿过胎盘屏障。加巴喷丁对胎儿大脑发育的影响尚未得到充分研究，这给临床处方决策带来了困难。使用三维神经元细胞培养研究了产前加巴喷丁暴露对腹侧中脑多巴胺能神经元发育的后果影响。使用定时交配的瑞士小鼠来分离胚胎。切除中脑腹侧三分之一部分并用于在随后暴露于加巴喷丁的三维细胞培养中富集多巴胺能群体。研究了加巴喷丁对腹侧中脑多巴胺能神经元的活力、ATP释放、形态发生和基因表达的影响。治疗水平的加巴喷丁治疗通过引起形态变化和关键发育基因表达的改变，干扰了胎儿大脑中腹侧中脑多巴胺能神经元的神经发生和形态发生，如TH + 总神经突长度和优势神经突长度显著改变。我们还发现加巴喷丁可以通过阻断ATP的产生来使这些神经元细胞的代谢状态停止。我们的研究结果清楚地表明加巴喷丁阻碍了多巴胺能神经元的形态发生和发育。这意味着加巴喷丁的使用可能会在育龄妇女中导致严重并发症。因此，在对孕妇处方加巴喷丁的临床决策中必须谨慎行事。
