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Effect of nicotine administration on development of muscarinic receptor in central nervous system of rat neonate

尼古丁给药对新生大鼠中枢神经系统毒蕈碱受体发育的影响

基本信息

批准号：
11670084
负责人：
TANIGUCHI Takanobu
金额：
$ 0.38万
依托单位：
Fukui Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670084/
关键词：
Nicotine Muscarinic receptor Choline transporter Rat neonate brain Development コリントランスポータ-

项目摘要

Rat fetuses or neonates were exposed to nicotine by administering nicotine to pregnant or lactating dams to estimate effects of nicotine on the development of cholinergic nervous system in brain of rat neonates. Since up-regulation of nicotinic receptor in rat neonates by nicotine administration has been already shown, we focussed on muscarinic receptor.1) We employed [^3H] QNB as a ligand to estimate muscarinic receptor. The level of muscarinic receptor in cerebral cortex started to develop just after birth and linearly increased to reach adult level 5 weeks after birth. Cerebellum showed a similar time course of muscarinic receptor development. However, in midbrain and hippocampus the level reached 80 % and in brainstem it reached 100 % of the adult level at 2 weeks after birth.2) We used pirenzepine as M1 specific and AF-DX116 as M2 specific ligands to examine the proportion of subtype of muscarinic receptor. Cerebral cortex and hippocampus were M1 dominant whereas cerebellum, midbrain and brainstem were M2 dominant tissues.3) We investigated the development of choline transporter, which is a specific marker for cholinergic post-synaptic terminal, by using [^3H] hemicholinium-3. Choline transporter in cerebral cortex started to develop after birth and reached 80 % of the adult level at 2 weeks after birth, as similarly seen in muscarinic receptor development in midbrain or hippocampus.4) Nicotine administration delayed the development of muscarinic receptor in cerebral cortex and cerebellum and delayed also that of choline transporter. These delays caught up with the normal time course at 5 weeks after birth.In conclusion, the present study demonstrates that perinatal nicotine treatment causes a developmental delay of muscarinic nervous system in rat neonates. These data can help us to understand one possible mechanism of the toxicity of cigarette smoking, as it related to brain development and the cause of neurological disorders

通过给妊娠或哺乳期大鼠喂尼古丁，使大鼠胎儿或新生儿暴露于尼古丁环境中，以评估尼古丁对大鼠新生儿脑胆碱能神经系统发育的影响。由于尼古丁给药对新生大鼠尼古丁受体的上调作用已经被证实，因此我们将重点放在毒蕈碱受体上。1)我们采用[^3H] QNB作为配体来估计毒蕈碱受体。大脑皮层毒蕈碱受体水平在出生后刚开始发育，在出生后5周呈线性增加，达到成人水平。小脑毒蕈碱受体发育的时间过程相似。而在出生后2周，中脑和海马的水平达到成人水平的80%，脑干达到成人水平的100%。2)以吡renzepine为M1特异性配体，AF-DX116为M2特异性配体，检测毒蕈碱受体亚型的比例。大脑皮层和海马为M1优势组织，小脑、中脑和脑干为M2优势组织。3)利用[^3H] hemholium -3研究了胆碱转运体（choline transporter）的发展，该转运体是胆碱能突触后末端的特异性标记物。大脑皮层胆碱转运体在出生后开始发育，出生后2周达到成人水平的80%，中脑或海马的毒蕈碱受体发育也类似。4)给药后脑皮层和小脑内毒蕈碱受体发育迟缓，胆碱转运体发育迟缓。这些延迟在出生后5周赶上了正常的时间进程。总之，本研究表明，围产期尼古丁治疗可导致大鼠新生儿毒蕈神经系统发育迟缓。这些数据可以帮助我们了解吸烟毒性的一种可能机制，因为它与大脑发育和神经系统疾病的原因有关