Sewell Leslie, Cray James J
Department of Biomedical Education and Anatomy, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Divisions of Biosciences and Orthodontics, College of Dentistry, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2025 Jun 20;20(6):e0325529. doi: 10.1371/journal.pone.0325529. eCollection 2025.
Nicotine exposure during neural development presents a significant public health concern. Nicotine, the primary addictive component of tobacco, influences the central nervous system by interacting with various cell types, including the glial cell termed astrocytes. Astrocytes are cells that are critical for supporting neurons, regulating neurotransmitter balance, and managing neuroinflammation. This current study explored nicotine's effects on astrocytes, examining cellular activity and gene expression within an acute exposure period. Murine C8D1A astrocytic (garnered as a cell line from postnatal day 8 tissue) cells were treated with nicotine (0-500 ng/mL) in vitro, with assays measuring cell viability and apoptosis at 12, 18, 24, and 48 hours to establish a critical concentration gradient for nicotine. Nicotine exposure increased astrocyte viability at later time points (24 and 48 hours), while apoptosis rose initially but declined over time allowing for the establishment of pharmacologically and clinically relevant nicotine concentrations of 25,50 and 100ng/ml for subsequent experiments. Real-time quantitative PCR revealed that nicotine influenced inflammatory signaling, with pro-inflammatory (A1) markers (IL-6, IFNγ, TNFα) increasing in a dose- and time-dependent manner, while anti-inflammatory (A2) markers (ARG1, IL-10, TGFβ) displayed a more complex pattern after nicotine exposures to astrocytes. These results suggest that nicotine disrupts astrocyte function and inflammatory balance, which may contribute to neurodevelopmental disruptions and heightened neuroinflammatory risks in adults. Further research is needed to investigate the prolonged impact of nicotine on brain health, addiction, and associated neurological conditions.
神经发育过程中接触尼古丁是一个重大的公共卫生问题。尼古丁是烟草的主要成瘾成分，它通过与包括称为星形胶质细胞的神经胶质细胞在内的各种细胞类型相互作用来影响中枢神经系统。星形胶质细胞对于支持神经元、调节神经递质平衡和控制神经炎症至关重要。本研究探讨了尼古丁对星形胶质细胞的影响，研究了急性暴露期内的细胞活性和基因表达。将小鼠C8D1A星形胶质细胞（从出生后第8天的组织中获取作为细胞系）在体外用尼古丁（0 - 500 ng/mL）处理，通过在12、18、24和48小时测量细胞活力和凋亡来确定尼古丁的临界浓度梯度。尼古丁暴露在后期时间点（24和48小时）增加了星形胶质细胞的活力，而凋亡最初上升但随时间下降，从而确定了后续实验中具有药理学和临床相关性的尼古丁浓度为25、50和100 ng/ml。实时定量PCR显示尼古丁影响炎症信号传导，促炎（A1）标志物（IL - 6、IFNγ、TNFα）呈剂量和时间依赖性增加，而抗炎（A2）标志物（ARG1、IL - 10、TGFβ）在尼古丁暴露于星形胶质细胞后呈现出更复杂的模式。这些结果表明尼古丁破坏了星形胶质细胞功能和炎症平衡，这可能导致神经发育紊乱以及成人神经炎症风险增加。需要进一步研究来调查尼古丁对大脑健康、成瘾及相关神经疾病的长期影响。
