Genes showing altered expression in the medial preoptic area in the highly social maternal phenotype are related to autism and other disorders with social deficits.
Genes showing altered expression in the medial preoptic area in the highly social maternal phenotype are related to autism and other disorders with social deficits.
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DOI：
10.1186/1471-2202-15-11
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发表时间：
2014-01-14
期刊：
影响因子：
2.4
通讯作者：
Gammie SC
中科院分区：
文献类型：
--
作者：
Driessen TM;Eisinger BE;Zhao C;Stevenson SA;Saul MC;Gammie SC
母子关系是哺乳动物最基本的社会纽带，之前的研究表明内侧视前区（MPOA）有助于这种社交能力的增加。在一种情况（母性状态）下导致社交能力提高的相同基因也可能在某些具有社交缺陷的疾病（例如自闭症）中失调。在这项研究中，我们检查了处女小鼠和产后雌性小鼠的 MPOA 微阵列结果中社交缺陷障碍相关基因是否存在富集（大于机会重叠）。我们利用微阵列来评估处女小鼠和产后小鼠 MPOA 中的大规模基因表达变化。模块化单组富集测试（MSET）用于确定精神健康障碍相关基因是否在显着的微阵列结果中富集。使用 ToppCluster、NIH DAVID 和加权共表达网络分析 (WGCNA) 等其他资源来分析特定基因簇的富集或重要感兴趣基因之间的间接关系。最后，使用定量 PCR 验证了微阵列结果的子集。显着的产后 MPOA 微阵列结果丰富了多种疾病，包括社交缺陷，包括自闭症、双相情感障碍、抑郁症和精神分裂症。从显着的微阵列结果中总共鉴定出了 98 个与自闭症相关的基因。此外，ToppCluser 和 NIH DAVID 鉴定了大量与离子通道活性和中枢神经系统发育相关的产后基因，并提示 microRNA 在调节母体基因表达中的作用。 WGCNA 鉴定了与产后表型相关的基因模块，并鉴定了转录因子与其他感兴趣基因之间的间接联系。向母性状态的转变涉及中枢神经系统的巨大可塑性和社交能力的增强。我们发现了多个在产后 MPOA（高社交性）和低社交性心理健康障碍之间重叠的新基因。因此，相同基因的活动或相互作用可能在不同条件下朝不同方向改变社会行为。怀孕还意味着罹患抑郁症、精神病和 BPD 等疾病的风险升高，因此识别这些疾病常见的母体基因可能有助于了解母体大脑的脆弱性。
The mother-child relationship is the most fundamental social bond in mammals, and previous studies indicate that the medial preoptic area (MPOA) contributes to this increase in sociability. It is possible that the same genes that lead to elevated sociability in one condition (the maternal state) might also be dysregulated in some disorders with social deficits (e.g. autism). In this study, we examined whether there was enrichment (greater than chance overlap) for social deficit disorder related genes in MPOA microarray results between virgin and postpartum female mice. We utilized microarrays to assess large scale gene expression changes in the MPOA of virgin and postpartum mice. The Modular Single Set Enrichment Test (MSET) was used to determine if mental health disorder related genes were enriched in significant microarray results. Additional resources, such as ToppCluster, NIH DAVID, and weighted co-expression network analysis (WGCNA) were used to analyze enrichment for specific gene clusters or indirect relationships between significant genes of interest. Finally, a subset of microarray results was validated using quantitative PCR. Significant postpartum MPOA microarray results were enriched for multiple disorders that include social deficits, including autism, bipolar disorder, depression, and schizophrenia. Together, 98 autism-related genes were identified from the significant microarray results. Further, ToppCluser and NIH DAVID identified a large number of postpartum genes related to ion channel activity and CNS development, and also suggested a role for microRNAs in regulating maternal gene expression. WGCNA identified a module of genes associated with the postpartum phenotype, and identified indirect links between transcription factors and other genes of interest. The transition to the maternal state involves great CNS plasticity and increased sociability. We identified multiple novel genes that overlap between the postpartum MPOA (high sociability) and mental health disorders with low sociability. Thus, the activity or interactions of the same genes may be altering social behaviors in different directions in different conditions. Maternity also involves elevated risks for disorders, including depression, psychosis, and BPD, so identification of maternal genes common to these disorders may provide insights into the elevated vulnerability of the maternal brain.
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影响因子：
3.7
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通讯作者：
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