title: Involvement of doublecortin-expressing cells in the arcuate nucleus in body weight regulation.
abstract: 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.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23538 Lübeck, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Werner
authors.forename: Helge
authors.initials: H
authors.lastname: Müller-Fielitz
authors.forename: Manuela
authors.initials: M
authors.lastname: Ritzal
authors.forename: Tim
authors.initials: T
authors.lastname: Werner
authors.forename: Moritz
authors.initials: M
authors.lastname: Rossner
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D001835:Body Weight / Q000235:genetics*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020738:Leptin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: C492588:Bsx protein, mouse; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018398:Homeodomain Proteins; D020738:Leptin; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050796:STAT3 Transcription Factor