促肾上腺皮质激素释放激素（CRH）反义寡脱氧核苷酸治疗可减轻社会挫败诱导的大鼠焦虑。
Corticotropin-releasing hormone (CRH) antisense oligodeoxynucleotide treatment attenuates social defeat-induced anxiety in rats.
作者信息
Skutella T, Montkowski A, Stöhr T, Probst J C, Landgraf R, Holsboer F, Jirikowski G F
机构信息
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
出版信息
Cell Mol Neurobiol. 1994 Oct;14(5):579-88. doi: 10.1007/BF02088839.
Abstract
- The neuropeptide corticotropin-releasing hormone (CRH) is the main mediator of the neuroendocrine and behavioral response to stress. End-capped phosphorothioate antisense and sense oligodeoxynucleotides (ODN) corresponding to the start coding region of rat CRH mRNA were infused intracerebroventricularly (30 micrograms/3 microliters per injection) three times at 12 hr intervals. Six hours after the last injection rats were subjected to social defeat stress and subsequently tested on the elevated plus maze. 2. Socially defeated CRH antisense-treated rats displayed markedly reduced anxiety-related behavior, as they spent significantly more time in the open arms of the plus maze compared to sense ODN- and vehicle-treated animals. 3. In controls, social defeat evoked a stress-induced elevation of CRH mRNA and CRH in the hypothalamus and a significant increase in plasma corticotropin (ACTH) levels. These parameters were attenuated in antisense-injected rats. 4. Our results suggest that CRH antisense treatment is effectively suppressing the neuroendocrine and behavioral effects of social defeat.
摘要
- 神经肽促肾上腺皮质激素释放激素（CRH）是应激时神经内分泌和行为反应的主要介质。将与大鼠CRH mRNA起始编码区对应的封端硫代磷酸酯反义寡脱氧核苷酸（ODN）和正义寡脱氧核苷酸（ODN）经脑室注射（每次注射30微克/3微升），每隔12小时注射一次，共注射三次。末次注射6小时后，将大鼠置于社会挫败应激环境中，随后在高架十字迷宫中进行测试。2. 经社会挫败处理且用CRH反义寡核苷酸处理的大鼠表现出焦虑相关行为明显减少，因为与用正义ODN和溶剂处理的动物相比，它们在十字迷宫开放臂中停留的时间明显更长。3. 在对照组中，社会挫败引起下丘脑CRH mRNA和CRH应激诱导性升高以及血浆促肾上腺皮质激素（ACTH）水平显著增加。这些参数在注射反义寡核苷酸的大鼠中减弱。4. 我们的结果表明，CRH反义寡核苷酸处理有效地抑制了社会挫败的神经内分泌和行为效应。
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