阿尔茨海默病小鼠脑内星形胶质细胞-神经元网络的相互作用受损  

Astrocyte-neuronal network interplay is disrupted in Alzheimer’s disease mice

作　　者：Justin Lines Andrés M Baraibar Cenxiao Fang Eduardo D Martin Juan Aguilar Michael K Lee Alfonso Araque Paulo Kofuji 杜一星(编译) Justin Lines;Andrés M Baraibar;Cenxiao Fang;Eduardo D Martin;Juan Aguilar;Michael K Lee;Alfonso Araque;Paulo Kofuji(Department of Neuroscience,University of Minnesota,Minneapolis,Minnesota,USA;Instituto Cajal,CSIC,Madrid,Spain;Experimental Neurophysiology and Neuronal Circuits,Hospital Nacional de Parapléjicos,SESCAM,Toledo,Spain.)

机构地区：[1]Department of Neuroscience,University of Minnesota,Minneapolis,Minnesota,USA [2]Instituto Cajal,CSIC,Madrid,Spain [3]Experimental Neurophysiology and Neuronal Circuits,Hospital Nacional de Parapléjicos,SESCAM,Toledo,Spain [4]不详

出　　处：《神经损伤与功能重建》2021年第12期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：阿尔茨海默病(AD)与影响神经元和星形胶质细胞功能的β-淀粉样蛋白(Aβ)老年斑有关。大脑活动源于星形胶质细胞-神经元网络中神经元和星形胶质细胞功能的相互协调,而Aβ对星形胶质细胞和神经元网络功能的影响仍然未知。我们同时监测星形胶质细胞钙活动和电神经元活动,将Aβ对AD小鼠感觉诱发皮质活动的影响进行量化。结果显示,在静息状态下,皮质星形胶质细胞表现出与Aβ密度相关的自发性过度活跃。AD小鼠中感觉诱发的星形胶质细胞反应减弱,反应强度取决于Aβ的密度和距离,并且显示钙活动动力学改变。即星形胶质细胞表现出自发性过度活跃,但对感觉刺激呈低反应。此外,AD小鼠表现出感觉诱发的皮质电活动高反应性与星形胶质细胞-神经元网络相互作用的改变相关。我们的研究结果表明,AD小鼠星形胶质细胞网络的功能障碍可能引起皮质电活动失调并导致认知能力下降。Alzheimer’s disease(AD) is associated with senile plaques of beta-amyloid(Aβ) that affect the function of neurons and astrocytes. Brain activity results from the coordinated function of neurons and astrocytes in astroglial-neuronal networks. However, the effects of Aβ on astroglial and neuronal network function remains unknown. Simultaneously monitoring astrocyte calcium and electric neuronal activities, we quantified the impact of Aβ on sensory-evoked cortical activity in a mouse model of AD. At rest, cortical astrocytes displayed spontaneous hyperactivity that was related to Aβ density. Sensory-evoked astrocyte responsiveness was diminished in AD mice, depending on the density and distance of Aβ, and the responses showed altered calcium dynamics. Hence, astrocytes were spontaneously hyperactive but hypo-responsive to sensory stimulation. Finally, AD mice showed sensory-evoked electrical cortical hyperresponsiveness associated with altered astrocyte-neuronal network interplay. Our findings suggest dysfunction of astrocyte networks in AD mice may dysregulate cortical electrical activity and contribute to cognitive decline.

关 键 词：APP/PS1(APP/PS1双转基因小鼠) 阿尔茨海默氏病 星形胶质细胞 星形胶质细胞增生症 β淀粉样蛋白 皮质 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]