Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA; Birth Defects Center, University of Louisville, Louisville, KY, USA.
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA.
Toxicology. 2014 Mar 20;317:40-9. doi: 10.1016/j.tox.2014.01.006. Epub 2014 Jan 28.
Exposure to cigarette smoke during development is linked to neurodevelopmental delays and cognitive impairment including impulsivity, attention deficit disorder, and lower IQ. However, brain region specific biomolecular alterations induced by developmental cigarette smoke exposure (CSE) remain largely unexplored. In the current molecular phenotyping study, a mouse model of 'active' developmental CSE (serum cotinine > 50 ng/mL) spanning pre-implantation through third trimester-equivalent brain development (gestational day (GD) 1 through postnatal day (PD) 21) was utilized. Hippocampus tissue collected at the time of cessation of exposure was processed for gel-based proteomic and non-targeted metabolomic profiling with partial least squares-discriminant analysis (PLS-DA) for selection of features of interest. Ingenuity pathway analysis was utilized to identify candidate molecular and metabolic pathways impacted within the hippocampus. CSE impacted glycolysis, oxidative phosphorylation, fatty acid metabolism, and neurodevelopment pathways within the developing hippocampus.
在发育过程中接触香烟烟雾与神经发育迟缓以及认知障碍有关，包括冲动、注意力缺陷障碍和智商降低。然而，发育性香烟烟雾暴露（CSE）引起的大脑区域特异性生物分子改变在很大程度上仍未得到探索。在当前的分子表型研究中，利用了一种“主动”发育性 CSE 的小鼠模型（血清可替宁>50ng/mL），该模型跨越了着床前到相当于第三个孕期的大脑发育（妊娠第 1 天到出生后第 21 天）。在暴露停止时收集海马组织，进行基于凝胶的蛋白质组学和非靶向代谢组学分析，并采用偏最小二乘判别分析（PLS-DA）选择感兴趣的特征。利用通路分析鉴定海马内受影响的候选分子和代谢途径。CSE 影响了发育中海马中的糖酵解、氧化磷酸化、脂肪酸代谢和神经发育途径。
