Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Academy of Military Sciences, Beijing, 100071, China; School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, 100871, China.
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Brain Res Bull. 2021 Sep;174:240-249. doi: 10.1016/j.brainresbull.2021.06.015. Epub 2021 Jun 25.
Repeated early environmental deprivation is regarded as a typical paradigm to mimic the behavioral abnormalities and brain dysfunction that occur in psychiatric disorders. Previously, we reported that social isolation could disrupt prepulse inhibition (PPI) in Sprague-Dawley (SD) rats, producing the typical characteristics of a schizophrenia animal model. Based on further analysis of previous proteomic and transcriptomic data, a disrupted balance of glucose metabolism was found in the prefrontal cortex (PFC) of isolated rats. Subsequently, in the first experiment of this study, we investigated the effects of juvenile social isolation (postnatal days (PND) 21-34) on PPI and lactate levels in PND56 rats. Compared with the social rearing group, rats in the isolated rearing group showed disrupted PPI and increased lactate levels in the PFC. In the second experiment, at PND55, the model rats were acutely injected with a glycogen phosphorylase inhibitor (4-dideoxy-1,4-imino-darabinitol, DAB) or control saline in the bilateral PFC. Our data showed that acute DAB administration (50 pmol, 0.5 μl) significantly improved the disrupted PPI and decreased the levels of oxidative phosphorylation (OXPHOS)-related mRNAs as well as lactate. In summary, our results suggested that excess astrocytic lactate production was involved in the impairment of auditory sensory gating of isolated rats, which may contribute to the metabolic pathogenesis of schizophrenia.
反复的早期环境剥夺被认为是模拟精神疾病中出现的行为异常和大脑功能障碍的典型范例。以前，我们报道过社交隔离会破坏 SD 大鼠的前脉冲抑制（PPI），产生精神分裂症动物模型的典型特征。基于对以前蛋白质组学和转录组学数据的进一步分析，发现孤立大鼠的前额叶皮层（PFC）中存在葡萄糖代谢失衡。随后，在这项研究的第一个实验中，我们研究了幼年社交隔离（PND21-34）对 PND56 大鼠 PPI 和 PFC 中乳酸水平的影响。与社交饲养组相比，隔离饲养组的大鼠表现出 PPI 破坏和 PFC 中乳酸水平升高。在第二个实验中，在 PND55 时，模型大鼠在双侧 PFC 中急性注射糖原磷酸化酶抑制剂（4-去氧-1,4-亚氨基-D-阿拉伯糖醇，DAB）或对照生理盐水。我们的数据显示，急性 DAB 给药（50pmol，0.5μl）显著改善了 PPI 的破坏，并降低了与氧化磷酸化（OXPHOS）相关的 mRNAs 以及乳酸的水平。总之，我们的结果表明，过量的星形胶质细胞乳酸产生参与了孤立大鼠听觉感觉门控的损害，这可能有助于精神分裂症的代谢发病机制。
