Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine
Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine
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DOI：
10.1016/s0169-328x(99)00048-0
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发表时间：
1999-04-06
期刊：
影响因子：
--
通讯作者：
Rattray, M
中科院分区：
文献类型：
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作者：
French, SJ;Humby, T;Rattray, M
将胆碱能受体激动剂尼古丁（烟碱型）、卡巴胆碱（烟碱型/毒蕈碱型）和毛果芸香碱（毒蕈碱型）注入海马，并使用原位杂交测定神经营养蛋白及其受体的 mRNA 水平。药物剂量经过精心选择，以避免癫痫发作和细胞死亡的潜在混淆效应。尼古丁导致海马体所有亚区神经生长因子 (NGF) mRNA 的持久增加。从给药后24小时到72小时，增加是明显的。这种增加依赖于兴奋性氨基酸神经传递，因为它可以被 AMPA 或 NMDA 受体拮抗剂阻断。相比之下，卡巴胆碱和毛果芸香碱在给药后4-8小时内产生NGF mRNA水平的短暂增加。毛果芸香碱引起海马脑源性神经营养因子（BDNF）水平短暂增加，卡巴胆碱和尼古丁也表现出相同的趋势。尼古丁和卡巴胆碱引起齿状回和 CA2 中 NT-3 mRNA 水平的短暂降低，毛果芸香碱也表现出类似的趋势。尼古丁摄入后 8 小时，编码全长 trkB 的 mRNA 增加，尼古丁还导致编码截短异构体 (trkB.T2) 的 mRNA 增加。 TrkC mRNA 不会因所用的任何条件而改变。该研究表明，海马体中毒蕈碱和烟碱受体的激活会导致所有神经营养素发生短暂变化，但烟碱受体刺激会选择性上调 NGF 水平。 NGF 和上行胆碱能系统之间的相互作用可能是尼古丁认知增强作用的一个组成部分。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Cholinergic receptor agonists nicotine (nicotinic), carbachol (nicotinic/muscarinic) and pilocarpine (muscarinic) were administered into the hippocampus and mRNA levels of neurotrophins and their receptors determined using in situ hybridisation. Drug doses were carefully chosen to avoid the potentially confounding effects of seizure and cell death. Nicotine caused a long-lasting increase in nerve growth factor (NGF) mRNA in all subfields of the hippocampus. The increase was evident from 24 h up to 72 h after drug administration. This increase was dependent on excitatory amino acid neurotransmission as it was blocked by administration of an AMPA or NMDA receptor antagonist. In contrast, carbachol and pilocarpine produced a transient increase in NGF mRNA levels present 4-8 h after drug administration. Pilocarpine caused a transient increase in hippocampal brain-derived neurotrophic factor (BDNF) levels, with carbachol and nicotine showing the same trend. Nicotine and carbachol caused transient decreases in NT-3 mRNA levels in dentate gyrus and CA2 with pilocarpine showing a similar trend. Increases in mRNA encoding full-length trkB were seen 8 h after nicotine, with nicotine also causing elevations in a mRNA encoding a truncated isoform (trkB.T2). TrkC mRNA was not altered by any of the conditions used. The study suggests that muscarinic and nicotinic receptor activation in the hippocampus causes transient changes in all of the neurotrophins, but that NGF levels are selectively up-regulated by nicotinic receptor stimulation. The reciprocal interaction between NGF and ascending cholinergic systems may be a component of the cognitive enhancing effects of nicotine. (C) 1999 Elsevier Science B.V. All rights reserved.