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老年斑形成和基底前脑胆碱能系统的退行性变 ,是阿尔茨海默病 (Alzheimer’sdisease ,AD)患者脑内的两个显著病理学特征。老年斑的主要成分是由 39～ 42个氨基酸残基构成的 β 淀粉样蛋白 (AβP) ;而胆碱能系统退行性变被认为是引起患者出现智力损伤的主要因素。长时程增强 (LTP)是由强直刺激作用于兴奋性突触传递通路所诱导的一种突触传递效率长时间增强的现象 ,长期以来被认为是信息储存过程中反映突触可塑性的电生理指标 ,与脊椎动物的某种学习、记忆机制有关。研究证明海马CA1区LTP的诱导主要通过谷氨酸能递质系统 ,特别是与NMDA受体的激活密切相关 ;同时也受到其他如胆碱能系统和GABA能系统等的调制。迄今为止 ,有关AβP对LTP影响的研究还不多 ,结论也不很一致。本实验采用脑片灌流的方法 ,以大鼠海马Schaffer侧支 /连合纤维 CA1锥体细胞这一通路上诱导的群集性峰电位 (populationspike ,PS)为观察指标 ;由于本实验室在神经元凋亡的实验和神经元单通道实验中发现 ,Aβ31 35可能是完整AβP的最短活性序列 ,本研究观察了人工合成的Aβ31- 35片段对LTP的影响 ,以期进一步探讨AβP沉积与胆碱能功能下降之间的可能联系 ;同时其作用也与较长片段Aβ2 5 35作了比较。结果表明 :① 0 .1μmol/LAβ31- 35?
Deterioration of senile plaques and degeneration of basal forebrain cholinergic system are two significant pathological features in the brain of patients with Alzheimer’s disease (AD). The major component of senile plaques is amyloid β (AβP) consisting of 39-42 amino acid residues. The degeneration of cholinergic system is considered to be the main cause of mental damage in patients. Long-term potentiation (LTP) is a phenomenon of long-term potentiation of synaptic transmission induced by tonic stimulation on excitatory synaptic transmission and has long been considered as electrophysiology reflecting synaptic plasticity during storage of information Indicators, and vertebrates some learning, memory mechanism. Studies have shown that the induction of LTP in the hippocampal CA1 region is mainly through the glutamatergic neurotransmitter system, especially the activation of NMDA receptors; it is also modulated by other systems such as cholinergic system and GABAergic system. So far, there is not much research on the effect of AβP on LTP, and the conclusions are not very consistent. In this study, brain slices perfusion method was used to observe the clustered peak potential (postspike, PS) induced by the rat hippocampal Schaffer collateral / conjunctiva CA1 pyramidal cells. Since the laboratory in neurons Apoptosis and neuron single-channel experiments found that Aβ31 35 may be the shortest active sequence of intact AβP. In this study, the effect of synthetic Aβ31-35 fragment on LTP was observed in order to further explore the relationship between AβP deposition and cholinergic function The possible link between the decline and its function was also compared with the longer fragment Aβ2 5 35. The results showed that: ①0.1μmol / LAβ31-35?