Greenfield S A, Appleyard M E, Bloomfield M R
Behav Brain Res. 1986 Jul;21(1):47-54. doi: 10.1016/0166-4328(86)90059-8.
In the substantia nigra, acetylcholinesterase may have a novel function related not to cholinergic transmission, but to the homeostasis of dopaminergic nigrostriatal neurones. The initial aim of this study was thus to see whether, in the rat, release of the enzyme into cerebrospinal fluid would reflect turning behaviour following unilateral 6-hydroxydopamine lesions of varying severity. It was found that acetylcholinesterase levels, lower than those in the cerebrospinal fluid of control rats, were accompanied by marginal circling behaviour and a small loss of striatal dopamine: on the other hand, elevated acetylcholinesterase activity was observed in the cerebrospinal fluid of rats displaying vigorous turning behaviour and with large depletion of striatal dopamine. It has already been demonstrated that exogenous acetylcholinesterase, applied locally to nigral neurones, has both electrophysiological and behavioural effects reminiscent of dopamine agonists. Hence it is possible that exogenous acetylcholinesterase could modify turning behaviour resulting from unilateral striatal dopamine depletion. Purified acetylcholinesterase, administered by cisternal puncture, attenuated circling behaviour for up to 7 days. The possible mechanisms are discussed by which endogenous acetylcholinesterase in cerebrospinal fluid could serve as an index of dopamine depletion in the nigrostriatal pathway and how exogenous enzymes might alleviate the accompanying motor dysfunction.
在黑质中，乙酰胆碱酯酶可能具有一种新功能，该功能并非与胆碱能传递相关，而是与多巴胺能黑质纹状体神经元的内环境稳定有关。因此，本研究的最初目的是观察在大鼠中，该酶释放到脑脊液中是否会反映出不同严重程度的单侧6-羟基多巴胺损伤后的旋转行为。研究发现，乙酰胆碱酯酶水平低于对照大鼠脑脊液中的水平时，伴有轻微的旋转行为和纹状体多巴胺少量丢失；另一方面，在表现出剧烈旋转行为且纹状体多巴胺大量耗竭的大鼠脑脊液中，观察到乙酰胆碱酯酶活性升高。已经证明，将外源性乙酰胆碱酯酶局部应用于黑质神经元，具有类似于多巴胺激动剂的电生理和行为效应。因此，外源性乙酰胆碱酯酶有可能改变单侧纹状体多巴胺耗竭导致的旋转行为。通过小脑延髓池穿刺给予纯化的乙酰胆碱酯酶，可使旋转行为减弱长达7天。文中讨论了脑脊液中的内源性乙酰胆碱酯酶可能作为黑质纹状体通路中多巴胺耗竭指标的可能机制，以及外源性酶可能减轻伴随的运动功能障碍的机制。
