Molecular Signalling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N107, NIH, Bethesda, MD 20892, USA.
Behav Genet. 2011 Sep;41(5):724-33. doi: 10.1007/s10519-011-9467-0. Epub 2011 Apr 12.
N-formylpeptide receptor 1 (FPR1) is a G protein-coupled receptor that mediates pro-inflammatory chemotactic responses by phagocytic leukocytes to N-formylpeptides produced by bacteria or mitochondria. Mice lacking Fpr1 (Fpr1 (-/-) mice) have increased susceptibility to challenge with certain bacteria. FPR1 is also a receptor for annexin-1, which mediates the anti-inflammatory effects of glucocorticoids as well as negative feedback by glucocorticoids of the hypothalamic-pituitary-adrenocortical axis. However, homeostatic functions of FPR1 in the neuroendocrine system have not previously been defined. Here we show that in systematic behavioral testing Fpr1 (-/-) mice exhibited increased exploratory activity, reduced anxiety-like behavior, and impaired fear memory, but normal spatial memory and learning capacity. Consistent with this, the homeostatic serum level of corticosterone in Fpr1 (-/-) mice was significantly lower compared with wild-type mice. The data implicate Fpr1 in modulation of anxiety-like behavior and fear memory by regulating glucocorticoid production.
N-甲酰肽受体 1（FPR1）是一种 G 蛋白偶联受体，可介导吞噬白细胞对细菌或线粒体产生的 N-甲酰肽的促炎趋化反应。缺乏 Fpr1 的小鼠（Fpr1（-/-）小鼠）对某些细菌的易感性增加。FPR1 也是 annexin-1 的受体，它介导了糖皮质激素的抗炎作用，以及糖皮质激素对下丘脑-垂体-肾上腺皮质轴的负反馈作用。然而，FPR1 在神经内分泌系统中的稳态功能以前尚未确定。在这里，我们表明，在系统行为测试中，Fpr1（-/-）小鼠表现出增加的探索活动、减少的焦虑样行为和受损的恐惧记忆，但空间记忆和学习能力正常。与此一致的是，与野生型小鼠相比，Fpr1（-/-）小鼠的稳态血清皮质酮水平显著降低。这些数据表明，Fpr1 通过调节糖皮质激素的产生来调节焦虑样行为和恐惧记忆。
