Hippocampal gene expression induced by cold swim stress depends on sex and handling
Hippocampal gene expression induced by cold swim stress depends on sex and handling
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DOI：
10.1016/j.psyneuen.2014.10.026
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发表时间：
2015-02-01
影响因子：
3.7
通讯作者：
Mansuy, Isabelle M.
中科院分区：
文献类型：
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作者：
Bohacek, Johannes;Manuella, Francesca;Mansuy, Isabelle M.
与压力有关的疾病，如创伤后应激障碍和抑郁症，在女性中比男性更普遍。这种不一致的原因之一可能是女性大脑中涉及压力反应的区域对压力更敏感。在这里，我们比较了急性应激对雌性和雄性小鼠海马中基因转录的影响，并研究了两种关键的应激相关激素皮质酮和促肾上腺皮质激素释放激素（Crh）的参与。采用定量逆转录聚合酶链反应（RT-qPCR）检测了短暂冷水胁迫45 min后Fos、Per 1和Sgk 1基因的表达。应激诱导的Fos和Per 1表达的女性比男性更强的增加。处理控制程序增加Fos在两种性别，但闭塞的影响，在男性的压力。此外，处理仅在雄性中增加Per 1。sgk 1是不敏感的处理，并增加了对压力的反应类似的队友和女性。游泳应激后观察到的转录变化没有模仿皮质酮注射，和应激诱导的Fos，Per 1和Sgk 1的增加既不能通过阻断糖皮质激素受体（GR），也不能通过阻断Crh受体1（Crhr 1）在应激暴露前。最后，我们证明了这种影响是应激特异性的，因为靶基因的表达不能通过短暂的束缚应激而增加，总之，我们发现急性游泳应激对海马基因表达的强烈影响，处理和性别之间的复杂相互作用，以及每个基因的独特反应模式。总的来说，女性应对冷水游泳的挑战与更强的海马基因转录比男性，独立的两个经典的介质的应激反应，皮质酮和Crh。这些发现可能对理解女性对某些与压力相关的神经精神疾病的更高脆弱性具有重要意义。(C)2014爱思唯尔有限公司版权所有。
Stress-related disorders such as PTSD and depression are more prevalent in women than men. One reason for such discordance may be that brain regions involved in stress responses are more sensitive to stress in females. Here, we compared the effects of acute stress on gene transcription in the hippocampus of female and male mice, and also examined the involvement of two key stress-related hormones, corticosterone and corticotropin releasing hormone (Crh). Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), we measured gene expression of Fos, Per1 and Sgk1 45 min after exposure to brief cold swim stress. Stress induced a stronger increase in Fos and Per1 expression in females than males. The handling control procedure increased Fos in both sexes, but occluded the effects of stress in males. Further, handling increased Per1 only in males. Sgk1 was insensitive to handling, and increased in response to stress similarly in mates and females. The transcriptional changes observed after swim stress were not mimicked by corticosterone injections, and the stress-induced increase in Fos, Per1 and Sgk1 could neither be prevented by pharmacologically blocking glucocorticoid receptor (GR) nor by blocking Crh receptor 1 (Crhr1) before stress exposure. Finally, we demonstrate that the effects are stressor-specific, as the expression of target genes could not be increased by brief restraint stress in either sex.In summary, we find strong effects of acute swim stress on hippocampal gene expression, complex interactions between handling and sex, and a remarkably unique response pattern for each gene. Overall, females respond to a cold swim challenge with stronger hippocampal gene transcription than males, independent of two classic mediators of the stress response, corticosterone and Crh. These findings may have important implications for understanding the higher vulnerability of women to certain stress-related neuropsychiatric diseases. (C) 2014 Elsevier Ltd. All rights reserved.