Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole.
Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole.
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DOI：
10.3109/10253890.2014.979785
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Schultz R
中科院分区：
文献类型：
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作者：
Grippo AJ;Moffitt JA;Henry MK;Firkins R;Senkler J;McNeal N;Wardwell J;Scotti MA;Dotson A;Schultz R
暴露于社会和环境压力源可能影响行为以及自主神经和心血管调节，可能导致抑郁症和心功能障碍，包括交感驱动升高，副交感神经功能降低和室性心律失常。这些相互作用背后的细胞机制尚不清楚。其中一种机制可能涉及心脏缝隙连接蛋白Connexin43 （Cx43）和Connexin45 （Cx45）表达的改变，这两种蛋白在确保细胞间有效偶联和维持心律方面发挥重要作用。本研究调查了草原田鼠（一种社会一夫一妻制的啮齿动物模型）长期的社会隔离和轻微的环境压力会产生抑郁行为和左心室Cx43和Cx45表达的改变。成年雌性草原田鼠分别暴露在社会隔离（n=22）或对照（n= 23）条件下（4周），单独或联合慢性轻度应激（1周）。与配对对照相比，社会隔离显著（P < 0.05）增加了5 min强迫游泳测试中的抑郁行为，慢性轻度应激加重了这些行为（P < 0.05）。社会隔离降低左心室Cx43总表达量（P < 0.05）；Western blot结果显示，慢性轻度应激（非隔离）增加了Cx45总表达量（P < 0.05），降低了Cx43/Cx45比值（P < 0.05）。目前的研究结果为草原田鼠与社会和环境压力相关的心律改变的潜在细胞机制提供了见解。
Exposure to social and environmental stressors may influence behavior as well as autonomic and cardiovascular regulation, potentially leading to depressive disorders and cardiac dysfunction including elevated sympathetic drive, reduced parasympathetic function, and ventricular arrhythmias. The cellular mechanisms that underlie these interactions are not well understood. One mechanism may involve alterations in the expression of Connexin43 (Cx43) and Connexin45 (Cx45), gap junction proteins in the heart that play an important role in ensuring efficient cell-to-cell coupling and the maintenance of cardiac rhythmicity. The present study investigated the hypothesis that long-term social isolation, combined with mild environmental stressors, would produce both depressive behaviors and altered Cx43 and Cx45 expression in the left ventricle of prairie voles – a socially monogamous rodent model. Adult, female prairie voles were exposed to either social isolation (n=22) or control (paired, n=23) conditions (4 weeks), alone or in combination with chronic mild stress (1 week). Social isolation, versus paired control conditions, produced significantly (P < 0.05) increased depressive behaviors in a 5-min forced swim test, and chronic mild stress exacerbated (P < 0.05) these behaviors. Social isolation (alone) reduced (P < 0.05) total Cx43 expression in the left ventricle; whereas chronic mild stress (but not isolation) increased (P < 0.05) total Cx45 expression and reduced (P < 0.05) the Cx43/Cx45 ratio, measured via Western blot analysis. The present findings provide insight into potential cellular mechanisms underlying altered cardiac rhythmicity associated with social and environmental stress in the prairie vole.