Gene expression profiling of high (HAB) vs. low (LAB) anxiety-related behavior mice in seven brain regions

Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) - centers of the central nervous anxiety and fear circuitries - were investigated and screened for differences between HAB and LAB mice. Analysis was performed from six animals per line (HAB and LAB, respectively) pooled per brain region in ten technical replicates, thereof five with a dye-swapped design giving a total of 70 array slides analyzed. The LAB mouse line is referred to as reference.为探究焦虑相关与抑郁样行为的分子基础及其相关关联因素，我们构建了高焦虑相关行为（High Anxiety-Related Behavior, HAB）与低焦虑相关行为（Low Anxiety-Related Behavior, LAB）小鼠模型。我们采用高架十字迷宫（elevated plus-maze）检测小鼠的焦虑相关行为遗传易感性，并以此作为动物近交繁育的筛选标准。在抑郁相关行为测试中，HAB小鼠相较于LAB小鼠展现出更为被动的抑郁样应对策略，这与精神疾病患者中观察到的焦虑与抑郁共病现象高度吻合。我们借助微阵列（microarray）技术，对中枢神经系统焦虑与恐惧环路的核心脑区——下丘脑室旁核（hypothalamic paraventricular nucleus, PVN）、基底外侧/外侧杏仁核（basolateral/lateral amygdala, BLA）、内侧杏仁核（medial amygdala, MeA）、中央杏仁核（central amygdala, CeA）、伏隔核（nucleus accumbens, NAc）、扣带回皮层（cingulate cortex, Cg）以及视上核（supraoptic nucleus, SON）——开展检测，并筛选HAB与LAB小鼠间的基因表达差异。本研究每个品系各取6只动物（分别对应HAB与LAB品系），按脑区混合样本后开展10次技术重复实验，其中5次采用染料互换实验设计，最终共计分析70张芯片玻片。本研究将LAB小鼠品系作为参照组。