Involvement of doublecortin-expressing cells in the arcuate nucleus in body weight regulation

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 CreERT2 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.