背景:由于早期生活压力(ELS)或父母精神病理学如精神分裂症(SZ)引起的不良经历对未来个体对精神疾病的易感性具有重要意义。然而,目前尚不完全了解ELS如何影响社会相关行为以及发育中的前额叶皮质(PFC).
目的:本研究的目的是调查ELS和氯胺酮诱导的精神分裂症样症状(KSZ)对快感缺失的影响,社会行为和焦虑样行为。
方法:将雄性和雌性Sprague-Dawley幼鼠随机分为八个实验组,即控制,妊娠压力(GS),GS+KSZ,母体分离(MS),MS+KSZ幼崽,KSZ父母,仅KSZ父母和幼犬和KSZ幼犬。通过对幼崽进行GS和MS诱导ELS,而精神分裂症样症状是通过皮下给予氯胺酮诱发的。行为评估包括蔗糖偏好测试(SPT)和高架迷宫(EPM),然后进行多巴胺检测和星形胶质细胞密度分析。统计分析涉及方差分析和事后Tukey检验,揭示显著的群体差异,并产生对行为和神经发育影响的见解。
结果:GS,MS,和KSZ(dams)显着降低了享乐反应,并增加了焦虑样反应(p<0.05)。值得注意的是,正常父母心理健康的存在证明了所观察到的胶质纤维酸性蛋白阳性星形胶质细胞(GFAP+星形胶质细胞)的下降(p<0.05)和焦虑水平的降低的逆转,暗示其对抑郁样症状和PFC星形胶质细胞功能的潜在保护性影响。
结论:本研究提供的经验证据支持以下假设:在SpragueDawley大鼠中,暴露于水坝上的ELS和KSZ对焦虑和抑郁样症状的发展有重大影响。而积极的育儿有逆转效应。
BACKGROUND: Adverse experiences due to early life stress (ELS) or parental psychopathology such as schizophrenia (SZ) have a significant implication on individual susceptibility to psychiatric disorders in the future. However, it is not fully understood how ELS affects social-associated behaviors as well as the developing prefrontal cortex (PFC).
OBJECTIVE: The aim of this study was to investigate the impact of ELS and ketamine induced schizophrenia like symptoms (KSZ) on anhedonia, social behavior and anxiety-like behavior.
METHODS: Male and female Sprague-Dawley rat pups were allocated randomly into eight experimental groups, namely control, gestational stress (GS), GS+KSZ, maternal separation (MS), MS+KSZ pups, KSZ parents, KSZ parents and Pups and KSZ pups only. ELS was induced by subjecting the pups to GS and MS, while schizophrenia like symptoms was induced through subcutaneous administration of ketamine. Behavioral assessment included sucrose preference test (SPT) and elevated plus maze (EPM), followed by dopamine testing and analysis of astrocyte density. Statistical analysis involved ANOVA and post hoc Tukey tests, revealing significant group differences and yielding insights into behavioral and neurodevelopmental impacts.
RESULTS: GS, MS, and KSZ (dams) significantly reduced hedonic response and increased anxiety-like responses (p < 0.05). Notably, the presence of normal parental mental health demonstrated a reversal of the observed decline in Glial Fibrillary Acidic Protein-positive astrocytes (GFAP+ astrocytes) (p < 0.05) and a reduction in anxiety levels, implying its potential protective influence on depressive-like symptoms and PFC astrocyte functionality.
CONCLUSIONS: The present study provides empirical evidence supporting the hypothesis that exposure to ELS and KSZ on dams have a significant impact on the on development of anxiety and depressive like symptoms in Sprague Dawley rats, while positive parenting has a reversal effect.