Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

Ren, Jing; Sun, Jinsheng; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

doi:10.1371/journal.pone.0052521

Cited by 13 publications

(18 citation statements)

References 54 publications

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“…To test the dosage dependent effects of nicotine on locomotor activity, we tested with four concentrations in addition to 0.6 mM of nicotine. In our previous study, we reported that 3.0 mM nicotine in food induced chronic locomotor hyperactivity (Ren et al, 2012). In this study, we found that acute treatment of nicotine at 3.0 mM induced locomotor hyperactivity in female flies, not however, in male flies.…”

Section: Nicotine Administration Induces Acute Locomotor Hyperactivitsupporting

confidence: 46%

“…In the startle-induced negative geotaxis assay using vertical columns, flies showed reduced climbing activity in response to nicotine treatment, and the acute and long-lasting effects were found to be mediated by dopaminergic system and cAMP/CREB pathway, respectively (Bainton et al, 2000, Hou et al, 2004. Using a video recording system where flies are tested in horizontal tubes (Zimmerman et al, 2008), our previous study revealed that chronic nicotine treatment induces locomotor hyperactivity in flies, and a protein in the decapping complex, decapping protein 2, was found to be a key factor in mediating nicotine-induced locomotor hyperactivity (Ren et al, 2012). Early onset of hyperactivity upon nicotine exposure has been observed in flies, though the mechanistic details behind this observation have so far not been studied (Bainton et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine-induced acute hyperactivity is mediated by dopaminergic system in a sexually dimorphic manner

Zhang

Guo

et al. 2016

Neuroscience

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Short-term exposure to nicotine induces positive effects in mice, monkeys and humans, including mild euphoria, hyperactivity, and enhanced cognition. However, the underlying neural basis and molecular mechanisms for these effects remain poorly understood. Here, using a video recording system, we find that acute nicotine administration induces locomotor hyperactivity in Drosophila, similar to observations made in higher model organisms. Suppressing dopaminergic neurons or down-regulating dopamine 1-like receptor (DopR) abolishes this acute nicotine response, but surprisingly, does so only in male flies. Using a GFP reconstitution across synaptic partners (GRASP) approach, we show that dopaminergic neurons possess potential synaptic connections with acetylcholinergic neurons in wide regions of the brain. Furthermore, dopaminergic neurons are widely activated upon nicotine perfusion in both sexes, while the response curve differs significantly between the sexes. Moreover, knockdown of the β1 nicotine acetylcholine receptor (nAChR) in dopaminergic neurons abolishes the acute nicotine response only in male flies, while panneural knock-down occurs in both sexes. Taken together, our results reveal that in fruit flies, dopaminergic neurons mediate nicotine-induced acute locomotor hyperactivity in a sexually dimorphic manner, and Drosophila β1 nAChR subunit plays a crucial role in this nicotine response. These findings provide important insights into the molecular and neural basis of acute nicotine effects, and the underlying mechanisms may play conserved roles across species.

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Section: Nicotine Administration Induces Acute Locomotor Hyperactivitsupporting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Nicotine-induced acute hyperactivity is mediated by dopaminergic system in a sexually dimorphic manner

Zhang

Guo

et al. 2016

Neuroscience

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“…The mRNA level for Dcp2 is upregulated 1.3-fold in the pcm 5 mutant, while its pre-mRNA is 1.1-fold downregulated. Although these changes are statistically significant, they are very small (< 30%) and unlikely to be biologically significant, because a 4-fold increase in Dcp2 protein level (by expression of a transgene) generates no mutant phenotypes when flies are grown under normal conditions 25 . For CG7966 and CG31157 , the mRNA levels of which do not change in the pcm 5 mutant, the pre-mRNA levels also do not change.…”

Section: Resultsmentioning

confidence: 93%

The 5′-3′ exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNAmiR-277–3pinDrosophilawing imaginal discs

Jones

Grima²,

Waldron

et al. 2013

RNA Biology

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Pacman/Xrn1 is a highly conserved exoribonuclease known to play a critical role in gene regulatory events such as control of mRNA stability, RNA interference and regulation via miRNAs. Although Pacman has been well studied in Drosophila tissue culture cells, the biologically relevant cellular pathways controlled by Pacman in natural tissues are unknown. This study shows that a hypomorphic mutation in pacman (pcm5) results in smaller wing imaginal discs. These tissues, found in the larva, are known to grow and differentiate to form wing and thorax structures in the adult fly. Using microarray analysis, followed by quantitative RT-PCR, we show that eight mRNAs were increased in level by > 2-fold in the pcm5 mutant wing discs compared with the control. The levels of pre-mRNAs were tested for five of these mRNAs; four did not increase in the pcm5 mutant, showing that they are regulated at the post-transcriptional level and, therefore, could be directly affected by Pacman. These transcripts include one that encodes the heat shock protein Hsp67Bc, which is upregulated 11.9-fold at the post-transcriptional level and 2.3-fold at the protein level. One miRNA, miR-277-3p, is 5.6-fold downregulated at the post-transcriptional level in mutant discs, suggesting that Pacman affects its processing in this tissue. Together, these data show that a relatively small number of mRNAs and miRNAs substantially change in abundance in pacman mutant wing imaginal discs. Since Hsp67Bc is known to regulate autophagy and protein synthesis, it is possible that Pacman may control the growth of wing imaginal discs by regulating these processes.

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“…More recently, Zhang et al showed that dopamine also mediates the chronic nicotine exposure-induced locomotor hyperactivity in adult flies described by Ren et al [42,69]. In mammals and Drosophila , alpha7 receptors have been associated to biogenic amine release [41,63].…”

Section: Discussionmentioning

confidence: 99%

A Drosophila model for developmental nicotine exposure

Velazquez-Ulloa

2017

PLoS ONE

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Despite the known health risks of tobacco smoking, many people including pregnant women continue smoking. The effects of developmental nicotine exposure are known, but the underlying mechanisms are not well understood. Drosophila melanogaster is a model organism that can be used for uncovering genetic and molecular mechanisms for drugs of abuse. Here I show that Drosophila can be a model to elucidate the mechanisms for nicotine’s effects on a developing organism. Drosophila reared on nicotine food display developmental and behavioral effects similar to those in mammals including decreased survival and weight, increased developmental time, and decreased sensitivity to acute nicotine and ethanol. The Drosophila nicotinic acetylcholine receptor subunit alpha 7 (Dα7) mediates some of these effects. A novel role for Dα7 on ethanol sedation in Drosophila is also shown. Future research taking advantage of the genetic and molecular tools for Drosophila will allow additional discovery of the mechanisms behind the effects of nicotine during development.

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Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

Cited by 13 publications

References 54 publications

Nicotine-induced acute hyperactivity is mediated by dopaminergic system in a sexually dimorphic manner

Nicotine-induced acute hyperactivity is mediated by dopaminergic system in a sexually dimorphic manner

The 5′-3′ exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNAmiR-277–3pinDrosophilawing imaginal discs

A Drosophila model for developmental nicotine exposure

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