Specific toxic effects of ethylcholine nitrogen mustard on cholinergic neurons of the nucleus basalis of Meynert

Specific toxic effects of ethylcholine nitrogen mustard on cholinergic neurons of the nucleus basalis of Meynert
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乙基胆碱氮芥对 Meynert 基底核胆碱能神经元的特异性毒性作用

DOI:
10.1016/0006-8993(86)91457-5
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发表时间:
1986
期刊:
影响因子:
2.9
通讯作者:
R. Arbogast
R. Arbogast
中科院分区:
医学3区
文献类型:
--
作者:
M. Kozlowski;R. Arbogast

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相似文献

将假定的胆碱能神经毒素乙基胆碱氮丙啶离子 (AF64A) 单侧注射到 Meynert 基底核 (nbM) 中,以确定其是否会对该核的胆碱能细胞体产生特异性损伤。注射少量 AF64A(1 μl 中 0.01 nmol)或其载体对 nbM 的外观或皮质中胆碱乙酰转移酶 (ChAT) 的水平几乎没有影响。注射较大量的 AF64A(1 μl 中 0.02 和 0.05 nmol,10 μl 中 0.02 nmol)会导致 nbM 中弥散性乙酰胆碱酯酶染色丧失,并导致大量阳性染色神经元丧失。此外,这些注射使皮质中央部分的 ChAT 活性显着降低。然而,nbM 区域的非胆碱能神经元并未受到这些 AF64A 注射的影响。此外,皮质对单胺的摄取不受这些病变的影响。 AF64A注射量的进一步增加(1μl中0.1nmol和10μl中0.35nmol)引起注射部位的损伤,不仅限于nbM的胆碱能元件。这些结果表明AF64A可用于产生胆碱能神经元的特定损伤,因此可用于开发涉及胆碱能功能减退的人类疾病的动物模型,例如阿尔茨海默型老年性痴呆。然而,产生这些特定效果的剂量范围很窄。
The putative cholinergic neurotoxin, ethylcholine aziridinium ion (AF64A), was injected unilaterally into the nucleus basalis of Meynert (nbM) in order to determine whether it would produce specific damage to the cholinergic cell bodies of this nucleus. Injections of small amounts of AF64A (0.01 nmol in 1 μl) or of its vehicle had little effect on the appearance of the nbM or on the levels of choline acetyltransferase (ChAT) in the cortex. Injections of larger amounts of AF64A (0.02 and 0.05 nmol in 1 μl and 0.02 nmol in 10 μl) produced a loss of difuse acetylcholinesterase staining in the nbM and a loss of large positively staining neurons. Furthermore, these injections produced a significant reduction of ChAT activity in the central portion of the cortex. However, non-cholinergic neurons in the area of the nbM were not affected by the these AF64A injections. In addition, cortical uptake of monoamines was not affected by these lesions. Further increases in the amount of AF64A injected (0.1 nmol in 1μl and 0.35 nmol in 10 μl) caused damage at the site of the injection which was not limited to the cholinergic elements of the nbM. These results suggest that AF64A canbe used to produce specific lesions of cholinergic neurons, and therefore may be useful in developing animal models of human disorders involving cholinergic hypofunction, such as senile dementia of the Alzheimer type. However, there is a narrow dose range for producing these specific effects.
DOI: 10.1126/science.6338589
发表时间: 1983-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
COYLE, JT;PRICE, DL;DELONG, MR
通讯作者: DELONG, MR