Amygdala gene expression correlates of social behavior in monkeys experiencing maternal separation
Amygdala gene expression correlates of social behavior in monkeys experiencing maternal separation
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DOI：
10.1523/jneurosci.4765-06.2007
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发表时间：
2007-03-21
影响因子：
5.3
通讯作者：
Mirnics, Karoly
中科院分区：
文献类型：
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作者：
Sabatini, Michael J.;Ebert, Philip;Mirnics, Karoly
早期因死亡或分居而失去父母的儿童未来罹患精神疾病（例如重度抑郁症和焦虑症）的风险更大。在 1 周龄时经历母亲分离的猴子在发育过程中表现出较少的社会行为和自我安慰行为（例如吮吸拇指）的增加，而相比之下，在 1 个月大时经历母亲分离的猴子在以后的生活中表现出更多的寻求社会安慰的行为。我们试图通过检查从分离 1 周、分离 1 个月和母亲抚养的 3 个月婴儿中收集的杏仁核组织中 mRNA 含量的变化来确定可能是这些压力诱导的行为变化背后的神经系统。使用 Affymetrix U133A 2.0 阵列分析来自右内侧颞叶（主要是杏仁核）的 mRNA。一种基因，鸟苷酸环化酶 1 α 3 (GUCY1A3)，在 1 周和母体饲养组以及 1 周和 1 个月组之间表现出差异表达；这些变化通过原位杂交得到证实。该基因的表达与急性社交安慰行为（r = 0.923；p = 0.001）和长期亲密社交行为（r = 0.708；p = 0.015）呈正相关，与自我安慰行为呈负相关（r = -0.88；p < 0.001）。在正常猴子中对 GUCY1A3 进行的其他原位杂交研究表明，该基因在 1 周龄时以成年水平表达，并且其在杏仁核中的表达高于所有其他检查的大脑区域。我们得出的结论是，GUCY1A3 可能会导致行为表型的改变，这些改变的表现取决于猕猴婴儿经历早期生活压力的年龄。
Children exposed to early parental loss from death or separation carry a greater risk for developing future psychiatric illnesses, such as major depression and anxiety. Monkeys experiencing maternal separation at 1 week of age show fewer social behaviors and an increase in self-comforting behaviors (e.g., thumb sucking) over development, whereas in contrast, monkeys experiencing maternal separation at 1 month of age show increased seeking of social comfort later in life. We sought to identify neural systems that may underlie these stress-induced behavioral changes by examining changes in mRNA content in amygdala tissue collected from 1 week separated, 1 month separated, and maternally reared infants at 3 months of age. mRNA from the right medial temporal lobe, primarily the amygdala, was analyzed using Affymetrix U133A 2.0 arrays. One gene, guanylate cyclase 1 alpha 3 (GUCY1A3), showed differential expression between the 1 week and maternally reared groups and the 1 week and 1 month groups; these changes were confirmed by in situ hybridization. The expression of this gene was positively correlated with acute social-comforting behavior (r = 0.923; p = 0.001) and longer-term close social behavior (r = 0.708; p = 0.015) and negatively correlated with self-comforting behaviors (r = -0.88; p < 0.001). Additional in situ hybridization studies of GUCY1A3 in normal monkeys showed that this gene is expressed at adult levels by 1 week of age and that its expression is greater in the amygdala than all other brain areas examined. We conclude that GUCY1A3 may contribute to the altered behavioral phenotypes that are differentially displayed depending on the age at which macaque infants experience an early-life stress.