Research Group of Proteomics & Biomarkers and Research Group of Psychoneuroendocrinology, Max Planck Institute of Psychiatry, Kraepelinstrasse 2, Munich, Germany.
Behav Brain Res. 2011 Jul 7;220(2):305-11. doi: 10.1016/j.bbr.2011.02.012. Epub 2011 Feb 21.
Several reports have implicated a role for the histidine triad nucleotide-binding protein-1 (Hint1) in psychiatric disorders. We have studied the emotional behaviour of male Hint1 knockout (Hint1 KO) mice in a battery of tests and performed biochemical analyses on brain tissue. The behavioural analysis revealed that Hint1 KO mice exhibit an increased emotionality phenotype compared to wildtype (WT) mice, while no significant differences in locomotion or general exploratory activity were noted. In the elevated plus-maze (EPM) test, the Hint1 KO animals entered the open arms of the apparatus less often than WT littermates. Similarly, in the dark-light box test, Hint1 KO mice spent less time in the lit compartment and the number of entries were reduced, which further confirmed an increased anxiety-related behaviour. Moreover, the Hint1 KO animals showed significantly more struggling and less floating behaviour in the forced swim test (FST), indicating an increased emotional arousal in aversive situations. Hint1 is known as a protein kinase C (PKC) interacting protein. Western blot analysis showed that PKCγ expression was elevated in Hint1 KO compared to WT mice. Interestingly, PKCγ mRNA levels of the two groups did not show a significant difference, implying a post-transcriptional PKCγ regulation. In addition, PKC enzymatic activity was increased in Hint1 KO compared to WT mice. In summary, our results indicate a role for Hint1 and PKCγ in modulating anxiety-related and stress-coping behaviour in mice.
几项报告表明组氨酸三联体核苷酸结合蛋白-1（Hint1）在精神疾病中起作用。我们研究了雄性 Hint1 敲除（Hint1 KO）小鼠在一系列测试中的情绪行为，并对脑组织进行了生化分析。行为分析表明，与野生型（WT）小鼠相比，Hint1 KO 小鼠表现出更高的情绪表型，而在运动或一般探索性活动中没有明显差异。在高架十字迷宫（EPM）测试中，与 WT 同窝仔相比，Hint1 KO 动物进入装置开放臂的次数较少。同样，在明暗箱测试中，Hint1 KO 小鼠在亮箱中的停留时间较少，进入次数减少，这进一步证实了焦虑相关行为的增加。此外，在强迫游泳测试（FST）中，Hint1 KO 动物表现出明显更多的挣扎和更少的漂浮行为，表明在厌恶情况下情绪唤醒增加。Hint1 被认为是蛋白激酶 C（PKC）相互作用蛋白。Western blot 分析显示，PKCγ 的表达在 Hint1 KO 小鼠中比 WT 小鼠升高。有趣的是，两组 PKCγ mRNA 水平没有显示出显著差异，暗示 PKCγ 的转录后调控。此外，PKC 酶活性在 Hint1 KO 小鼠中比 WT 小鼠增加。总之，我们的结果表明 Hint1 和 PKCγ 在调节小鼠的焦虑相关和应激应对行为中起作用。
