寡聚体Aβ_(1-42)对大鼠海马突触可塑性的慢性影响

Chronic effects of oligomeric Aβ_(1-42) on hippocampal synaptic plasticity in vivo

突触传递的长时程抑制(long-term depression,LTD)和长时程增强(long term-potentiation,LTP)是突触可塑性的两种重要形式,并且与学习记忆密切相关。本文探讨Sprague-Dawley(SD)大鼠在海马齿状回区(dentate gyrus,DG)注射36h孵育形成的寡聚体Aβ1-4230d后,在体海马前穿通纤维-齿状回通路(perforant path-dentate gyrus pathway,PP-DG)的突触可塑性和空间记忆能力的变化。2.5月龄SD大鼠随机分为寡聚体Aβ1-42注射组[即阿尔茨海默病(Alzheimer’s disease,AD)模型组,n=12]和正常对照组(n=12),分别在双侧海马DG区注射5μg寡聚体Aβ1-42或生理盐水。应用Morris水迷宫检测大鼠空间记忆能力。同时运用神经电生理在体胞外记录技术,检测寡聚体Aβ1-42引起的海马双脉冲易化(paired pulse facilitation,PPF)、LTD、LTP等突触可塑性形式的变化。结果显示:(1)AD模型组大鼠空间记忆能力下降(P<0.05);(2)寡聚体Aβ1-42降低海马PPF强度(P<0.05),并减小PPF宽度;(3)寡聚体Aβ1-42显著抑制海马LTP形成(P<0.05),而易化LTD形成(P<0.05)。上述结果提示:寡聚体Aβ1-42对海马PP-DG通路突触可塑性的破坏,会导致大鼠空间记忆功能障碍。

Synaptic plasticity,including long-term potentiation（LTP） and long-term depression（LTD）,is widely considered as one of the major mechanisms underlying learning and memory.This study explored hippocampal synaptic plasticity and spatial memory formation of an Alzheimer＇s disease（AD） rat model established by intrahippocampal injection of oligomeric Aβ1-42.Twenty four Sprague-Dawley rats at 2.5 months of age were randomly divided into AD and control groups,and were bilaterally injected with 5 μg oligomeric Aβ1-42 or normal saline into dentate gyrus（DG） of hippocampus.Morris water maze test was used to observe the capability of learning and memory of two groups,30 d after injection.To investigate the variations of paired-pulse facilitation（PPF） and range of synaptic plasticity,field potentials were recorded in the DG of the dorsal hippocampus by stimulating the perforant path（PP）.The results showed that oligomeric Aβ1-42 obviously impaired spatial memory formation in rats（P 0.05）.Furthermore,oligomeric Aβ1-42 reduced the PPF ratio（P 0.05） and hippocampal LTP formation（P 0.05）,while facilitated the hippocampal LTD formation（P 0.05）.These data suggest that chronic Aβ aggregation impairs synaptic plasticity of hippocampal PP-DG pathway,which may be involved in the spatial memory deficit in AD rats.