Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan.
Int J Mol Sci. 2023 Feb 20;24(4):4199. doi: 10.3390/ijms24044199.
In the pathogenesis of depression, heredity is believed to be a major factor. However, the mechanism by which heredity contributes to the onset of depression is not fully understood. Wistar Kyoto (WKY) rats have been used as an animal model for depression because of their increased depression-like behavior compared to Wistar (WIS) rats. In the present study, pups crossbred from WKY × WIS rats were used to evaluate locomotor activity in an open field test (OFT) and depression-like behavior in a forced swimming test (FST), with a focus on amino acid metabolism. Pups in the WKY♂ × WKY♀ group showed lower locomotor activity in the OFT and higher depression-like behavior in the FST than those in the WIS♂ × WIS♀ group. In addition, multiple regression analysis showed that the paternal strain had a greater effect than the maternal strain on locomotor activity and depression-like behavior in OFT and FST, respectively. Several amino acids in the brainstem, hippocampus, and striatum were significantly decreased through the influence of the WKY paternal strain, but not the WKY maternal strain. Based on these data from comparing WKY and WIS rats, we hypothesize that the hereditary effects of the WKY paternal strain on behavioral tests are partially caused by dysregulation of the amino acid metabolism in the brain.
在抑郁症的发病机制中，遗传被认为是一个主要因素。然而，遗传导致抑郁症发作的机制尚未完全阐明。Wistar 京都（WKY）大鼠因其与 Wistar（WIS）大鼠相比表现出更多的抑郁样行为而被用作抑郁症的动物模型。在本研究中，使用 WKY×WIS 大鼠杂交的幼崽来评估旷场试验（OFT）中的运动活动和强迫游泳试验（FST）中的抑郁样行为，重点关注氨基酸代谢。与 WIS♂×WIS♀组相比，WKY♂×WKY♀组的幼崽在 OFT 中的运动活动较低，在 FST 中的抑郁样行为较高。此外，多元回归分析表明，父本品系对 OFT 和 FST 中的运动活动和抑郁样行为的影响大于母本品系。通过 WKY 父本品系的影响，脑桥、海马和纹状体中的几种氨基酸显著降低，但 WKY 母本品系没有。基于 WKY 和 WIS 大鼠的这些数据，我们假设 WKY 父本品系对行为测试的遗传影响部分是由大脑中氨基酸代谢的失调引起的。
