Role of Nicotine in Regulation of naChRs in Drosophila
尼古丁在果蝇 naChR 调节中的作用
基本信息
- 批准号:6421777
- 负责人:
- 金额:$ 30.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-09-27 至 2006-06-30
- 项目状态:已结题
- 来源:
- 关键词:Drosophilidae cholinergic receptors cyclic AMP drug addiction genetically modified animals green fluorescent proteins invertebrate embryology microarray technology neural transmission neurogenetics neurons neuropharmacology nicotine pharmacogenetics polymerase chain reaction receptor expression synapses
项目摘要
DESCRIPTION (provided by applicant):
Modifications in the properties of nAChRs and excitatory synaptic transmission
in neurons are thought to play an important role in the process of nicotine
addiction in humans. However, the molecular mechanisms underlying behavioral
responses to nicotine remain poorly understood. In this grant we propose to
address these questions in a genetically accessible animal model. We have
recently described the properties of nAChRs that mediate fast excitatory
transmission in cultured Drosophila neurons. These cultures provide a unique
opportunity to explore the cellular and molecular mechanisms important in
regulation of nAChRs and cholinergic transmission at central synapses. Our
first aim focuses on characterizing the biophysical, pharmacological, and
molecular properties of nAChRs mediating nicotine-evoked currents/calcium
transients in Drosophila neurons. In addition we will determine the function of
different nAChR genes by examining the consequences of knocking out or reducing
the expression of specific subunit/s in the cultured neurons. This will be
accomplished by examining neurona! responses to nicotine in cultures prepared
from deficiencies uncovering nAChR genes or in cultures exposed to dsRNA
targeted to particular nAChR subunit/s.
The second aim examines the role of nicotine in regulation of nAChRs and
cholinergic transmission. Neuronal responses to nicotinefACh, 1125-aBTX
binding, and the properties of cholinergic transmission will be monitored in
neurons chronically exposed to nicotine. We will also examine the effects of
short duration, repetitive treatments with nicotine, mimicking the exposure
that occurs during smoking. The cAMP signaling cascade plays a role in
regulating responses to ethanol and cocaine in both flies and mammals. In our
third aim we will examine the properties of nAChRs and cholinergic synaptic
currents in cAMP signaling mutants to determine if the effects of nicotine are
also modulated by CAMP. Finally, we will use differential display and cDNA
microarrays to identify genes that are differentially regulated by nicotine.
The results of our studies will provide important insights into the mo!ecular
mechanisms underlying nicotine-induced regulation of nAChRs. These data will
also contribute to the general understanding of the molecular mechanisms
important in regulating transmission at excitatory synapses, likely to be
highly conserved between vertebrates and invertebrates. Finally, this knowledge
may be useful in the design of drugs ancVor therapies targeted at ameliorating
or preventing nicotine addiction in humans by regulating nAChRs and synaptic
function.
描述(由申请人提供):
NAChRs特性的改变与兴奋性突触传递
神经元被认为在尼古丁的过程中起着重要作用
人类的毒瘾。然而,行为背后的分子机制
人们对尼古丁的反应仍然知之甚少。在这笔赠款中,我们建议
用一种可遗传的动物模型来解决这些问题。我们有
最近描述了nAChRs介导快速兴奋的特性
培养的果蝇神经元中的传递。这些文化提供了一种独特的
有机会探索重要的细胞和分子机制
中枢突触nAChRs和胆碱能传递的调节。我们的
第一个目标集中在表征生物物理,药理和
NAChRs介导尼古丁诱发电流/钙的分子特性
果蝇神经元中的瞬变。此外,我们还将确定
通过检测敲除或减少的后果来区分不同的nAChR基因
培养神经元中特异性亚单位/S的表达。这将是
通过检查神经细胞完成的!准备好的培养物对尼古丁的反应
由于发现nAChR基因的缺陷或暴露于dsRNA的培养
靶向特定的nAChR亚单位/S
第二个目的是研究尼古丁在nAChRs和nAChRs调节中的作用
胆碱能传递。尼古丁对ACh,1125-aBTX的神经元反应
结合,胆碱能传递的特性将在
长期接触尼古丁的神经元。我们还将研究以下方面的影响
持续时间短,重复尼古丁治疗,模拟暴露
那是在吸烟时发生的。CAMP信号级联在
调节果蝇和哺乳动物对乙醇和可卡因的反应。在我们的
第三,我们将研究nAChRs和胆碱能突触的特性
CAMP信号突变体中的电流以确定尼古丁的影响是否
也受阵营的影响。最后,我们将使用差异显示和cDNA
用于识别尼古丁差异调控基因的微阵列。
我们的研究结果将为研究分子提供重要的见解。
尼古丁诱导nAChRs调节的潜在机制。这些数据将
也有助于对分子机制的一般理解。
在调节兴奋性突触的传递方面很重要,可能是
在脊椎动物和无脊椎动物之间高度保守。最后,这个知识
可能在针对改善的药物或疗法的设计中有用
或通过调节nAChRs和突触来预防人类的尼古丁成瘾
功能。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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DIANE K O'DOWD其他文献
DIANE K O'DOWD的其他文献
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{{ truncateString('DIANE K O'DOWD', 18)}}的其他基金
Functional studies of epilepsy mutations in Drosophila and human iPSC-derived neu
果蝇和人类 iPSC 衍生神经元癫痫突变的功能研究
- 批准号:
9208170 - 财政年份:2014
- 资助金额:
$ 30.08万 - 项目类别:
Functional studies of epilepsy mutations in Drosophila and human iPSC-derived neu
果蝇和人类 iPSC 衍生神经元癫痫突变的功能研究
- 批准号:
8990893 - 财政年份:2014
- 资助金额:
$ 30.08万 - 项目类别:
Functional studies of epilepsy mutations in Drosophila and human iPSC-derived neu
果蝇和人类 iPSC 衍生神经元癫痫突变的功能研究
- 批准号:
8690664 - 财政年份:2014
- 资助金额:
$ 30.08万 - 项目类别:
PILOT STUDY--NICOTINE ROLE IN REGULATION OF NACHR IN DROSOPHILA
试点研究--尼古丁对果蝇 NACHR 调节的作用
- 批准号:
6660949 - 财政年份:2002
- 资助金额:
$ 30.08万 - 项目类别:
PILOT STUDY--NICOTINE ROLE IN REGULATION OF NACHR IN DROSOPHILA
试点研究--尼古丁在果蝇 NACHR 调节中的作用
- 批准号:
6495109 - 财政年份:2001
- 资助金额:
$ 30.08万 - 项目类别:
Role of Nicotine in Regulation of naChRs in Drosophila
尼古丁在果蝇 naChR 调节中的作用
- 批准号:
6634396 - 财政年份:2001
- 资助金额:
$ 30.08万 - 项目类别:
Role of Nicotine in Regulation of naChRs in Drosophila
尼古丁在果蝇 naChR 调节中的作用
- 批准号:
6776893 - 财政年份:2001
- 资助金额:
$ 30.08万 - 项目类别:
Role of Nicotine in Regulation of naChRs in Drosophila
尼古丁在果蝇 naChR 调节中的作用
- 批准号:
6914142 - 财政年份:2001
- 资助金额:
$ 30.08万 - 项目类别:
Role of Nicotine in Regulation of naChRs in Drosophila
尼古丁在果蝇 naChR 调节中的作用
- 批准号:
6515952 - 财政年份:2001
- 资助金额:
$ 30.08万 - 项目类别:
PILOT STUDY--NICOTINE ROLE IN REGULATION OF NACHR IN DROSOPHILA
试点研究--尼古丁在果蝇 NACHR 调节中的作用
- 批准号:
6349045 - 财政年份:2000
- 资助金额:
$ 30.08万 - 项目类别:
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