Kelley D Parker, Chaichi Ardalan, Duplooy Alexander, Singh Dhirendra, Gartia Manas Ranjan, Francis Joseph
Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, 70803, USA.
Department of Mechanical and Industrial Engineering, Louisiana State University, Baton Rouge, LA, 70803, USA.
Neurobiol Stress. 2022 Aug 11;20:100476. doi: 10.1016/j.ynstr.2022.100476. eCollection 2022 Sep.
Oxidative and lipid homeostasis are altered by stress and trauma and post-traumatic stress disorder (PTSD) is associated with alterations to lipid species in plasma. Stress-induced alterations to lipid oxidative and homeostasis may exacerbate PTSD pathology, but few preclinical investigations of stress-induced lipidomic changes in the brain exist. Currently available techniques for the quantification of lipid species in biological samples require tissue extraction and are limited in their ability to retrieve spatial information. Raman imaging can overcome this limitation through the quantification of lipid species in minimally processed tissue slices. Here, we utilized a predator exposure and psychosocial stress (PE/PSS) model of traumatic stress to standardize Raman imaging of lipid species in the hippocampus using LC-MS based lipidomics and these data were confirmed with qRT-PCR measures of mRNA expression of relevant enzymes and transporters. Electron Paramagnetic Resonance Spectroscopy (EPR) was used to measure free radical production and an MDA assay to measure oxidized polyunsaturated fatty acids. We observed that PE/PSS is associated with increased cholesterol, altered lipid concentrations, increased free radical production and reduced oxidized polyunsaturated fats (PUFAs) in the hippocampus (HPC), indicating shifts in lipid and oxidative homeostasis in the HPC after traumatic stress.
氧化和脂质稳态会因应激和创伤而改变，创伤后应激障碍（PTSD）与血浆中脂质种类的改变有关。应激诱导的脂质氧化和稳态改变可能会加剧PTSD病理，但目前很少有关于应激诱导大脑脂质组学变化的临床前研究。目前用于定量生物样品中脂质种类的技术需要组织提取，并且在获取空间信息的能力方面有限。拉曼成像可以通过对最少处理的组织切片中的脂质种类进行定量来克服这一限制。在这里，我们利用创伤应激的捕食者暴露和心理社会应激（PE/PSS）模型，使用基于液相色谱-质谱联用（LC-MS）的脂质组学对海马体中脂质种类进行拉曼成像标准化，并用相关酶和转运蛋白的mRNA表达的定量逆转录聚合酶链反应（qRT-PCR）测量来证实这些数据。电子顺磁共振光谱（EPR）用于测量自由基产生，丙二醛（MDA）测定用于测量氧化的多不饱和脂肪酸。我们观察到，PE/PSS与海马体（HPC）中胆固醇增加、脂质浓度改变、自由基产生增加以及氧化多不饱和脂肪（PUFA）减少有关，表明创伤应激后HPC中脂质和氧化稳态发生了变化。
