Meng Fan-Tao, Zhao Jun, Fang Hui, Zhang Li-Feng, Wu Hui-Mei, Liu Ya-Jing
CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, Anhui, People's Republic of China.
Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China.
Behav Genet. 2017 Jul;47(4):416-424. doi: 10.1007/s10519-017-9843-5. Epub 2017 Mar 24.
Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice. However, corticotropin releasing factor levels in the hypothalamus and plasma corticosterone secretion were similar in GFAP-ApoE3 and GFAP-ApoE4 transgenic male mice. Additionally, increased expression of the mineralocorticoid receptor (MR) and unchanged expression of the glucocorticoid receptor were observed in the hypothalamus of GFAP-ApoE4 mice. However, no significant differences were found in the expression levels of the MR in GFAP-ApoE3 and GFAP-ApoE4 mice at postnatal day 2. In conclusion, we found that MR upregulation rather than corticosterone level changes in the early stage of adulthood was associated with the higher anxiety-like level measured in GFAP-ApoE4 mice.
焦虑症状在很大一部分阿尔茨海默病（AD）患者中出现。载脂蛋白E-4（ApoE ε4等位基因）作为AD的一个风险因素，已被认为是导致精神障碍的一个重要因素。在本研究中，我们旨在调查具有不同胶质纤维酸性蛋白（GFAP）-ApoE异构体的转基因雄性小鼠中皮质酮水平与焦虑样行为变化之间的关系。与年龄匹配的GFAP-ApoE3小鼠相比，3个月大的GFAP-ApoE4转基因小鼠在旷场试验、明暗箱试验和高架十字迷宫试验中表现出更高的焦虑样行为。然而，GFAP-ApoE3和GFAP-ApoE4转基因雄性小鼠下丘脑促肾上腺皮质激素释放因子水平和血浆皮质酮分泌相似。此外，在GFAP-ApoE4小鼠的下丘脑中观察到盐皮质激素受体（MR）的表达增加，而糖皮质激素受体的表达没有变化。然而，在出生后第2天，GFAP-ApoE3和GFAP-ApoE4小鼠的MR表达水平没有显著差异。总之，我们发现成年早期MR上调而非皮质酮水平变化与GFAP-ApoE4小鼠中测得的较高焦虑样水平相关。
