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Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in
Jing Ren1, Jinghan Sun, Yunpeng Zhang
1State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
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.
Insights
Chronic nicotine exposure causes hyperactivity in fruit flies by down-regulating Decapping Protein 2 (Dcp2). This finding reveals the mRNA decapping pathway
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Nicotine dependence from tobacco use involves complex gene regulation and neurotransmitter pathways.
- Signaling mechanisms linking nicotine's molecular effects to behavioral changes are not fully understood.
- Decapping proteins, crucial for mRNA degradation, have largely uninvestigated roles in the nervous system.
Purpose of the Study:
- To investigate the molecular pathways underlying chronic nicotine exposure's behavioral effects.
- To identify key factors involved in nicotine-induced locomotor activity changes.
- To explore the role of mRNA decapping in nicotine dependence.
Main Methods:
- Utilized a chronic nicotine administration paradigm in adult male fruit flies (Drosophila).
- Assessed locomotor activity following repeated nicotine exposure.
- Generated and analyzed flies deficient in Decapping Protein 1 (Dcp1) and Decapping Protein 2 (Dcp2).
- Quantified Dcp2 messenger RNA (mRNA) levels in fly heads.
- Manipulated Dcp2 expression in the nervous system.
Main Results:
- Chronic nicotine exposure induced significant locomotor hyperactivity in wild-type flies.
- This hyperactivity was abolished in Dcp2-deficient flies, implicating Dcp2 in the response.
- Nicotine treatment suppressed Dcp2 mRNA levels in fly heads.
- Upregulating Dcp2 expression in the nervous system prevented nicotine-induced hyperactivity.
- Dcp2 deficiency alone led to higher basal locomotor activity.
Conclusions:
- Down-regulation of Dcp2 mediates chronic nicotine-induced locomotor hyperactivity in Drosophila.
- The mRNA decapping pathway plays a significant role in behavioral responses to chronic nicotine.
- Dcp2 is identified as a key factor in nicotine dependence and warrants further investigation.
