Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice

被引:113
作者
Karolyi, IJ
Burrows, HL
Ramesh, TM
Nakajima, M
Lesh, JS
Seong, E
Camper, SA
Seasholtz, AF
机构
[1] Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Program Mol & Cellular Biol, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Program Neurosci, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA
关键词
D O I
10.1073/pnas.96.20.11595
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Corticotropin-releasing hormone (CRH) is widely recognized as the primary mediator of the neuroendocrine and behavioral responses to stress, including stress-induced anxiety. The biological activity of CRH and other mammalian CRH-like peptides, such as urocortin, may be modulated by CRH-binding protein (CRH-BP). To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting. Basal adrenocorticotropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corticosterone after restraint stress. In contrast, adult male CRH-BP-deficient mice show significantly reduced body weight when compared with wild-type controls. CRH-BP-deficient mice also exhibit a significant increase in anxiogenic-like behavior as assessed by the elevated plus maze and defensive withdrawal tests. The increased anorectic and anxiogenic-like behavior most likely is caused by increased "free" CRH and/or urocortin levels in the brain of CRH-BP-deficient animals, suggesting an important role for CRH-BP in maintaining appropriate levels of these peptides in the central nervous system.
引用
收藏
页码:11595 / 11600
页数:6
相关论文
共 33 条
[1]   DISPLACEMENT OF CORTICOTROPIN-RELEASING FACTOR FROM ITS BINDING-PROTEIN AS A POSSIBLE TREATMENT FOR ALZHEIMERS-DISEASE [J].
BEHAN, DP ;
HEINRICHS, SC ;
TRONCOSO, JC ;
LIU, XJ ;
KAWAS, CH ;
LING, N ;
DESOUZA, EB .
NATURE, 1995, 378 (6554) :284-287
[2]   ISOLATION OF THE HUMAN-PLASMA CORTICOTROPHIN-RELEASING FACTOR-BINDING PROTEIN [J].
BEHAN, DP ;
LINTON, EA ;
LOWRY, PJ .
JOURNAL OF ENDOCRINOLOGY, 1989, 122 (01) :23-31
[3]  
Behan DP, 1997, J NEUROCHEM, V68, P2053
[4]  
Bradley A., 1987, TERATOCARCINOMAS EMB, P113
[5]   Excess corticotropin releasing hormone-binding protein in the hypothalamic-pituitary-adrenal axis in transgenic mice [J].
Burrows, HL ;
Nakajima, M ;
Lesh, JS ;
Goosens, KA ;
Samuelson, LC ;
Inui, A ;
Camper, SA ;
Seasholtz, AF .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (07) :1439-1447
[6]   Corticotrophin-releasing factor receptors: From molecular biology to drug design [J].
Chalmers, DT ;
Lovenberg, TW ;
Grigoriadis, DE ;
Behan, DP ;
DeSouza, EB .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1996, 17 (04) :166-172
[7]   MOLECULAR AND BIOCHEMICAL-CHARACTERIZATION OF THE MOUSE-BRAIN CORTICOTROPIN-RELEASING HORMONE-BINDING PROTEIN [J].
CORTRIGHT, DN ;
NICOLETTI, A ;
SEASHOLTZ, AF .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1995, 111 (02) :147-157
[8]   PHYSIOLOGICAL AND BEHAVIORAL-RESPONSES TO CORTICOTROPIN-RELEASING FACTOR ADMINISTRATION - IS CRF A MEDIATOR OF ANXIETY OR STRESS RESPONSES [J].
DUNN, AJ ;
BERRIDGE, CW .
BRAIN RESEARCH REVIEWS, 1990, 15 (02) :71-100
[9]  
HARRO J, 1993, METHODS NEUROSCIENCE, V14, P359
[10]   Corticotropin-releasing factor CRF1, but not CRF2, receptors mediate anxiogenic-like behavior [J].
Heinrichs, SC ;
Lapsansky, J ;
Lovenberg, TW ;
DeSouza, EB ;
Chalmers, DT .
REGULATORY PEPTIDES, 1997, 71 (01) :15-21