Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the α subunit of the heterotrimeric G-protein Gq
Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the α subunit of the heterotrimeric G-protein Gq
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DOI：
10.1523/jneurosci.4632-06.2007
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发表时间：
2007-02-07
影响因子：
5.3
通讯作者：
Schmauss, Claudia
中科院分区：
文献类型：
--
作者：
Bhansali, Punita;Dunning, Jane;Schmauss, Claudia
婴儿母亲分离是啮齿动物早期生活压力的一种范例，它引发了持续到成年的基因表达的长期变化。BALB/c小鼠是一种具有自发升高的焦虑和应激反应的近交系小鼠，婴儿母分离导致对成年应激的抑郁样行为反应增加，并显著增加5 -羟色胺2C受体前mrna的编辑。慢性氟西汀治疗暴露于早期生活应激的成年BALB/c小鼠既不影响其对应激的行为反应，也不影响其基础5-HT2C mrna前编辑表型。然而，当在青春期给予氟西汀时，这些小鼠对压力的抑郁样行为反应显着减少，并且它们的基础和应激诱导的5-HT2C pre-mRNA编辑表型显着降低。此外，当暴露于早期生活压力的BALB/c小鼠在断奶后丰富的环境中长大时，它们对成年应激的抑郁样行为反应也显著减少。然而，他们的5-HT2C前mrna编辑表型保持不变。因此，在青春期，富集和氟西汀治疗的类似行为效应并不伴随着5-HT2C pre-mRNA编辑的类似变化。暴露于早期生活应激的富集和非富集BALB/c小鼠也表现出编码与5-HT2A/2C受体偶联的G蛋白的G α q亚基的mRNA和蛋白质的显著增加。相比之下，氟西汀处理小鼠的G α q表达水平显著降低。这些发现表明，在5-HT2C前mrna编辑持续改变的小鼠中，G α q表达发生代偿性变化，并为5-HT2C受体编辑表型与行为应激反应之间的分离提供了解释。
Infant maternal separation, a paradigm of early life stress in rodents, elicits long-lasting changes in gene expression that persist into adulthood. In BALB/c mice, an inbred strain with spontaneously elevated anxiety and stress reactivity, infant maternal separation led to increased depression-like behavioral responses to adult stress and robustly increased editing of serotonin 2C receptor pre-mRNA. Chronic fluoxetine treatment of adult BALB/c mice exposed to early life stress affected neither their behavioral responses to stress nor their basal 5-HT2C pre-mRNA editing phenotype. However, when fluoxetine was administered during adolescence, depression-like behavioral responses to stress were significantly diminished in these mice, and their basal and stress-induced 5-HT2C pre-mRNA editing phenotypes were significantly lower. Moreover, when BALB/c mice exposed to early life stress were raised in an enriched postweaning environment, their depression-like behavioral responses to adult stress were also significantly diminished. However, their 5-HT2C pre-mRNA editing phenotype remained unaltered. Hence, the similar behavioral effects of enrichment and fluoxetine treatment during adolescence were not accompanied by similar changes in 5-HT2C pre-mRNA editing. Enriched and nonenriched BALB/c mice exposed to early life stress also exhibited significantly increased expression of mRNA and protein encoding the G alpha q subunit of G-protein that couples to 5-HT2A/2C receptors. In contrast, G alpha q expression levels were significantly lower in fluoxetine-treated mice. These findings suggest that compensatory changes in G alpha q expression occur in mice with persistently altered 5-HT2C pre-mRNA editing and provide an explanation for the dissociation between 5-HT2C receptor editing phenotypes and behavioral stress responses.