Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys.
Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys.
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DOI：
10.1111/j.1471-4159.2009.06011.x
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发表时间：
2009-05
影响因子：
4.7
通讯作者：
Quik M
中科院分区：
文献类型：
--
作者：
Huang LZ;Parameswaran N;Bordia T;Michael McIntosh J;Quik M
在黑质纹状体损伤前给予尼古丁可减少帕金森病动物的多巴胺能缺陷。在这里，我们测试了尼古丁是否也对已有黑质纹状体损伤的大鼠和猴子有益。在内侧前脑束单侧6-羟基多巴胺（6-OHDA）损伤之前和之后给大鼠施用尼古丁，并将结果与仅在损伤后给大鼠尼古丁的结果进行比较。尼古丁预处理减轻了行为缺陷，并减少了纹状体多巴胺转运蛋白以及α6β2* 和α4β2* 烟碱受体（nAChR）的损伤诱导损失。相比之下，在损伤后两周给予尼古丁，此时6-OHDA诱导的神经退行性作用基本完成，并没有改善这些相同的措施。在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）损伤的猴子中观察到类似的结果。尼古丁没有增强纹状体标记物时，给予猴子预先存在的黑质纹状体损伤，与以往的数据显示，改善时，尼古丁给猴子损伤前。在两种动物模型中的这些综合研究结果表明，尼古丁对黑质纹状体损伤具有神经保护作用，而不是神经恢复作用。接下来进行了125 I-α-芋螺毒素MII（α-CtxMII）和α-CtxMII类似物E11 A的受体研究，以确定尼古丁处理前或损伤后是否差异影响纹状体中α6α4β2* 和α6（非α4）β2* nAChR亚型的表达。观察结果表明，针对黑质纹状体损伤的保护可能与纹状体α6α4β2* nAChRs有关。
Nicotine reduces dopaminergic deficits in parkinsonian animals when administered before nigrostriatal damage. Here we tested whether nicotine is also beneficial when given to rats and monkeys with pre-existing nigrostriatal damage. Rats were administered nicotine before and after a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, and the results compared to those in which rats received nicotine only after lesioning. Nicotine pretreatment attenuated behavioral deficits and lessened lesion-induced losses of the striatal dopamine transporter, and α6β2* and α4β2* nicotinic receptors (nAChRs). In contrast, nicotine administered two weeks after lesioning, when 6-OHDA-induced neurodegenerative effects are essentially complete, did not improve these same measures. Similar results were observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys. Nicotine did not enhance striatal markers when administered to monkeys with pre-existing nigrostriatal damage, in contrast to previous data that showed improvements when nicotine was given to monkeys before lesioning. These combined findings in two animal models suggest that nicotine is neuroprotective rather than neurorestorative against nigrostriatal damage. Receptor studies with 125I-α-conotoxinMII (α-CtxMII) and the α-CtxMII analog E11A were next done to determine whether nicotine treatment pre- or post-lesioning differentially affected expression of α6α4β2* and α6(nonα4)β2* nAChR subtypes in striatum. The observations suggest that protection against nigrostriatal damage may be linked to striatal α6α4β2* nAChRs.
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影响因子：
3.6
作者：
Bordia, Tanuja;Grady, Sharon R.;Quik, Maryka
通讯作者：
Quik, Maryka
DOI：
10.1124/jpet.106.106997
发表时间：
2006-10-01
影响因子：
3.5
作者：
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通讯作者：
Quik, Maryka
影响因子：
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作者：
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通讯作者：
Dajas, Federico
影响因子：
5.3
作者：
Meshul, CK;Kamel, D;Krentz, L
通讯作者：
Krentz, L
影响因子：
4.2
作者：
Belluardo, N;Mudò, G;Fuxe, K
通讯作者：
Fuxe, K