adult raphe-specific deletion of lmx1b leads to central serotonin deficiency成人raphe-specific删除lmx1b导致中枢5 -羟色胺不足.pdfVIP

Adult Raphe-Specific Deletion of Lmx1b Leads to Central Serotonin Deficiency 1 1 1 1 1 2 Ning-Ning Song *, Jian-Bo Xiu , Ying Huang , Jia-Yin Chen , Lei Zhang , Lise Gutknecht , Klaus Peter 2 3 1 Lesch , He Li , Yu-Qiang Ding * 1 Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China, 2 Molecular and Clinical Psychobiology, Department of Psychiatry ¨ ¨ and Psychotherapy, University of Wurzburg, Wurzburg, Germany, 3 Key Laboratory of Nervous System Diseases, Ministry of Education of China, Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Abstract The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreERT2 mice were generated and crossed with Lmx1bflox/flox mice to obtain Pet1-CreERT2; Lmx1bflox/flox mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchang