Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA.
Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA.
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DOI：
10.1016/j.neuroscience.2013.10.064
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发表时间：
2014-01-31
期刊：
影响因子：
3.3
通讯作者：
Barr G
中科院分区：
文献类型：
--
作者：
Sarro EC;Sullivan RM;Barr G
焦虑相关障碍是最常见的精神疾病之一，被认为有遗传和环境原因。早期生活创伤，如来自照顾者的虐待，可以是可预测的，也可以是不可预测的，每一种创伤都会导致一组独特疾病的发病率和严重程度增加。在这项研究中，我们研究了早期不可预测的创伤对成人焦虑行为表达和杏仁核内基因表达的影响。将新生大鼠暴露在不配对的气味-休克条件下5天，产生成年行为缺陷和杏仁核功能障碍。在成年期，我们使用Light/Dark box测试来测量焦虑相关行为，测量进入光照区域的潜伏期，并量化排尿和排便。然后解剖杏仁核并进行微阵列分析以检查基因表达的变化。早期受到不可预测的创伤的动物表现出明显更长的进入光照区域的潜伏期和更多的排便和排尿。微阵列分析显示，与学习和记忆、突触传递和跨膜运输相关的基因被过度代表。基因本体和通路分析确定了与焦虑表型相关的高度代表性疾病状态，包括社交焦虑、强迫症、创伤后应激障碍和双相情感障碍。在该分析中，成瘾相关基因也被过度代表。早期发育过程中不可预测的休克会增加成年后的焦虑样行为，并伴随神经传递相关基因的变化，导致类似于焦虑相关精神疾病的基因表达模式。
Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, PTSD and bipolar disorder. Addiction related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders.