Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23538 Lübeck, Germany.
Endocrinology. 2012 Jun;153(6):2655-64. doi: 10.1210/en.2011-1760. Epub 2012 Apr 4.
Hypothalamic functions, including feeding behavior, show a high degree of plasticity throughout life. Doublecortin (DCX) is a marker of plasticity and neuronal migration expressed in the hypothalamus. Therefore, we wanted to map the fate of DCX(+) cells in the arcuate nucleus (ARC) of the hypothalamus. For this purpose, we generated a BAC transgenic mouse line that expresses the inducible recombinase CreER(T2) under control of the DCX locus. Crossing this line with the Rosa26 or Ai14 reporter mouse lines, we found reporter(+) cells in the ARC upon tamoxifen treatment. They were born prenatally and expressed both DCX and the plasticity marker TUC-4. Immediately after labeling, reporter(+) cells had an enlarged soma that normalized over time, suggesting morphological remodeling. Reporter(+) cells expressed β-endorphin and BSX, neuronal markers of the feeding circuit. Furthermore, leptin treatment led to phosphorylation of STAT3 in reporter(+) cells in accordance with the concept that they are part of the feeding circuits. Indeed, we found a negative correlation between the number of reporter(+) cells and body weight and epididymal fat pads. Our data suggest that DCX(+) cells in the ARC represent a cellular correlate of plasticity that is involved in controlling energy balance in adult mice.
下丘脑功能，包括摄食行为，在整个生命过程中表现出高度的可塑性。双皮质醇（DCX）是一种可塑性和神经元迁移的标志物，在下丘脑表达。因此，我们想要绘制下丘脑弓状核（ARC）中 DCX(+)细胞的命运图。为此，我们生成了一种 BAC 转基因小鼠品系，该品系在 DCX 基因座的控制下表达可诱导的重组酶 CreER(T2)。通过与 Rosa26 或 Ai14 报告小鼠品系杂交，我们发现经他莫昔芬处理后，ARC 中有报告基因(+)细胞。它们在产前产生，并表达 DCX 和可塑性标志物 TUC-4。标记后立即，报告基因(+)细胞的胞体增大，随着时间的推移恢复正常，表明发生了形态重塑。报告基因(+)细胞表达β-内啡肽和 BSX，这是摄食回路的神经元标志物。此外，瘦素处理导致报告基因(+)细胞中 STAT3 的磷酸化，符合它们是摄食回路一部分的概念。事实上，我们发现报告基因(+)细胞的数量与体重和附睾脂肪垫呈负相关。我们的数据表明，ARC 中的 DCX(+)细胞代表参与控制成年小鼠能量平衡的可塑性的细胞相关性。
