Upregulation of Mineralocorticoid Receptor in the Hypothalamus Associated with a High Anxiety-like Level in Apolipoprotein E4 Transgenic Mice.
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.
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.
Fan-Tao
FT
Meng
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. zjun@mail.ustc.edu.cn.|Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China. zjun@mail.ustc.edu.cn.
Jun
J
Zhao
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.
Hui
H
Fang
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.
Li-Feng
LF
Zhang
Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People's Republic of China.
Hui-Mei
HM
Wu
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People's Republic of China. yjl@ustc.edu.cn.|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. yjl@ustc.edu.cn.
Ya-Jing
YJ
Liu
D000544:Alzheimer Disease / Q000378:metabolism / Q000523:psychology*; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System; D007031:Hypothalamus; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010913:Pituitary-Adrenal System; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005904:Glial Fibrillary Acidic Protein; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid
Anxiety-like; Apolipoprotein E; Corticotropin releasing factor; Glucocorticoid receptor; Hypothalamic–pituitary–adrenal axis; Mineralocorticoid receptor