title: Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.
abstract: Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.
authors.affiliation: State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.forename: Jinghan
authors.initials: J
authors.lastname: Sun
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Ren
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Aike
authors.initials: A
authors.lastname: Guo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D055785:Gene Knockdown Techniques; D006948:Hyperkinesis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D009538:Nicotine / Q000009:adverse effects*; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C470831:Lcp2 protein, Drosophila; D014157:Transcription Factors; D009538:Nicotine