中枢神经递质ACh和NE与Alzheimer病的认知功能
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摘要
目的：
本实验主要借助事件相关电位的主要成分之一—P300来研究在大鼠海马
NE能或ACh能系统损伤条件下，其认知功能发生的改变，据此来分析海马内的
这两种主要的神经递质（NE及ACh）在学习记忆中所发挥的重要作用，及其相
互作用的神经机制。并通过观察海马内分别缺失这两种神经递质条件下所发生的
突触可塑性变化，从而将形态与功能结合起来，以期对AD的病因学研究方面提
供理论依据。
方法：
1．通过手术横断大鼠左侧穹窿—海马伞（FF）方法对海马内的胆碱能神经作物
理性切除；建立系统损伤模型，通过向大鼠双侧背去甲肾上腺素束注射
6-OHDA方法对海马内的去甲肾上腺素能神经作化学性切除。
2．在建模前后对其进行迷宫测试及类P3潜伏期及振幅的测定。
3．在NE能或ACh能系统缺失条件下，用TIGER细胞图像分析系统对大鼠海
马CA3区的GrayⅠ型突触电镜图像进行定量分析，测定突触后膜致密物质
厚度、突触间隙宽度、突触界面曲率和突触活性带长度等结构参数。
结果：
实验表明，海马内NE能或ACh能神经系统的失常均可导致：
1．动物的记忆保持力显著下降。
2．大鼠类P3潜伏期较对照组有显著延长，并与迷宫测试指标（EN、TRT）成
正相关关系，但在两个实验组之间未见有显著性差异。
3．突触后膜致密物质厚度明显变薄，突触间隙宽度加大变宽、突出界面曲率减
小。此外，穿孔性突触的比例也有不同程度的变化。
结论：
1．海马内乙酰胆碱与去甲肾上腺素的正常水平对动物认知能力的保持是必要的，
它们相互制约，处于生理平衡状态。如这种平衡状态被破坏，认知功能将处
于病理状态。
2．乙酞胆碱与去甲肾上腺素在P300的产生与整合机制中占有重要地位。两种递
质系统的损伤，均将导致P300波形的变化．
3．海马神经元功能状态和突触连接强度的维持是学习记忆的重要物质基础。
4．基于缺失NE及ACh在功能学与形态学上具有相一致的变化趋势，可以推测
这两种神经递质间可能具有复杂的协同作用。这两种递质的失调可能是老年
痴呆发病的重要因素，本研究对临床老年痴呆的防治提供了理论依据。
Purpose:
To study the change of cognitive function by mensurating amplitude and latency
of one of the major component in ERP-P300 when the ACh or NE neurotransmitter in
hippocampus was derogated. So analysis the important function of this two type (ACh
and NE) neurotransmitters on learning and memory, and the complex correlation
Besides, this study also observed the synaptic plasticity in CA3 neurons of
hippocampus, so combine conformation with function. We wish this experiment can
offer theoretical warranty for study on AD.
Methods:
1. ACh system lesion model was made by severing fimbrial-fornix(FF) transaction,
NE system impairment model by injection of 6-hydroxysopamine into the bilateral
dorsal noradrenergic bundle in DG.
2. Then Y-type maze test and elicitation of P3-like latency and amplitude were
carried out separately before and after the all models were built.
3. The electron micro graphs of Gray I type synapses in the hippocampus of rats
were quantitatively analyzed by means of an TIGER cell image processing system.
Measured parameters included the thickness of postsynaptic density, the width of
synaptic cleft, the curvature of synaptic interface, and the length of active zone.
Results:
In either two experiment group,the breakdown of NE or Ach neuron system in
hippocampus can lead to:
1. The ability of memory retention was decreased significantly.
2. P3-like latency were prolonged statistically as compared with the controls and had
positive correlation with indices of Y-maze test (EN, TRT),but have no signally
difference between the two experiment group.
3. The thickness of postsynaptic density (PSD) and the curvature of synaptic
interface was reduced; while the width of synaptic cleft were remarkably
increased. In the meantime, the occurrence of perforated synapses were also
changed in the hippocampus CA3 areas.
Conclusion:
I. It is necessary for maintain of memory retention that normal Ach and NE level in
hippocainpus, they condition each other , maintain in balance of physiological
level.
2. ACh and NE are important mechanisms in produce and conformity of P3-like
potential.
3. The functional state of the hippocampal neurons and the nomal connection of
synapses played an importuned role in cognition and memory.
4. As the similar change occur in the breaking of Ach or NE in hippocampus, we
suggest that the Ach and NE in hippocampus have a involved synergetic
relationship,the disfunction of this two chemical system may be an important
factor in production of AD.This study offer theoretical warranty for prevention
and cure of clinical of AD.
本实验主要借助事件相关电位的主要成分之一—P300来研究在大鼠海马
NE能或ACh能系统损伤条件下，其认知功能发生的改变，据此来分析海马内的
这两种主要的神经递质（NE及ACh）在学习记忆中所发挥的重要作用，及其相
互作用的神经机制。并通过观察海马内分别缺失这两种神经递质条件下所发生的
突触可塑性变化，从而将形态与功能结合起来，以期对AD的病因学研究方面提
供理论依据。
方法：
1．通过手术横断大鼠左侧穹窿—海马伞（FF）方法对海马内的胆碱能神经作物
理性切除；建立系统损伤模型，通过向大鼠双侧背去甲肾上腺素束注射
6-OHDA方法对海马内的去甲肾上腺素能神经作化学性切除。
2．在建模前后对其进行迷宫测试及类P3潜伏期及振幅的测定。
3．在NE能或ACh能系统缺失条件下，用TIGER细胞图像分析系统对大鼠海
马CA3区的GrayⅠ型突触电镜图像进行定量分析，测定突触后膜致密物质
厚度、突触间隙宽度、突触界面曲率和突触活性带长度等结构参数。
结果：
实验表明，海马内NE能或ACh能神经系统的失常均可导致：
1．动物的记忆保持力显著下降。
2．大鼠类P3潜伏期较对照组有显著延长，并与迷宫测试指标（EN、TRT）成
正相关关系，但在两个实验组之间未见有显著性差异。
3．突触后膜致密物质厚度明显变薄，突触间隙宽度加大变宽、突出界面曲率减
小。此外，穿孔性突触的比例也有不同程度的变化。
结论：
1．海马内乙酰胆碱与去甲肾上腺素的正常水平对动物认知能力的保持是必要的，
它们相互制约，处于生理平衡状态。如这种平衡状态被破坏，认知功能将处
于病理状态。
2．乙酞胆碱与去甲肾上腺素在P300的产生与整合机制中占有重要地位。两种递
质系统的损伤，均将导致P300波形的变化．
3．海马神经元功能状态和突触连接强度的维持是学习记忆的重要物质基础。
4．基于缺失NE及ACh在功能学与形态学上具有相一致的变化趋势，可以推测
这两种神经递质间可能具有复杂的协同作用。这两种递质的失调可能是老年
痴呆发病的重要因素，本研究对临床老年痴呆的防治提供了理论依据。
Purpose:
To study the change of cognitive function by mensurating amplitude and latency
of one of the major component in ERP-P300 when the ACh or NE neurotransmitter in
hippocampus was derogated. So analysis the important function of this two type (ACh
and NE) neurotransmitters on learning and memory, and the complex correlation
Besides, this study also observed the synaptic plasticity in CA3 neurons of
hippocampus, so combine conformation with function. We wish this experiment can
offer theoretical warranty for study on AD.
Methods:
1. ACh system lesion model was made by severing fimbrial-fornix(FF) transaction,
NE system impairment model by injection of 6-hydroxysopamine into the bilateral
dorsal noradrenergic bundle in DG.
2. Then Y-type maze test and elicitation of P3-like latency and amplitude were
carried out separately before and after the all models were built.
3. The electron micro graphs of Gray I type synapses in the hippocampus of rats
were quantitatively analyzed by means of an TIGER cell image processing system.
Measured parameters included the thickness of postsynaptic density, the width of
synaptic cleft, the curvature of synaptic interface, and the length of active zone.
Results:
In either two experiment group,the breakdown of NE or Ach neuron system in
hippocampus can lead to:
1. The ability of memory retention was decreased significantly.
2. P3-like latency were prolonged statistically as compared with the controls and had
positive correlation with indices of Y-maze test (EN, TRT),but have no signally
difference between the two experiment group.
3. The thickness of postsynaptic density (PSD) and the curvature of synaptic
interface was reduced; while the width of synaptic cleft were remarkably
increased. In the meantime, the occurrence of perforated synapses were also
changed in the hippocampus CA3 areas.
Conclusion:
I. It is necessary for maintain of memory retention that normal Ach and NE level in
hippocainpus, they condition each other , maintain in balance of physiological
level.
2. ACh and NE are important mechanisms in produce and conformity of P3-like
potential.
3. The functional state of the hippocampal neurons and the nomal connection of
synapses played an importuned role in cognition and memory.
4. As the similar change occur in the breaking of Ach or NE in hippocampus, we
suggest that the Ach and NE in hippocampus have a involved synergetic
relationship,the disfunction of this two chemical system may be an important
factor in production of AD.This study offer theoretical warranty for prevention
and cure of clinical of AD.
引文
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