Vesicular glutamate transporter and cognition in stroke A case-control autopsy study
Vesicular glutamate transporter and cognition in stroke A case-control autopsy study
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DOI：
10.1212/wnl.0b013e3181fd6328
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发表时间：
2010-11-16
期刊：
影响因子：
9.9
通讯作者：
Francis, P. T.
中科院分区：
文献类型：
--
作者：
Kirvell, S. L.;Elliott, M. S.;Francis, P. T.
目的：血管性痴呆(VaD)约占所有痴呆的15%-20%，但进行性认知损害与神经化学变化的关系尚不清楚。因此，我们对VAD的谷氨酸能突触标志物进行了研究。方法：我们使用两个新皮质区域(Brodmann区[BA]9和BA 20)灰质制备的匀浆和Western blotting来测定谷氨酸能神经递质系统的关键成分、囊泡性谷氨酸转运体1(VGLUT1)和兴奋性氨基酸转运体EAAT2(GLT-1)的浓度，以及普遍存在的突触蛋白突触蛋白Synaptophysin。结果：在病例对照设计中，BA20和BA 9的VGLUT1浓度与CAMCOG总量(0.525Rs，25Rs)相关P=0.018，n=20；0.560卢比，p=0.002，n=27)和CAMCOG记忆分数(0.616卢比，p=0.004，n=20；0.675卢比，p=0.000，n=27)。VGLUT1在不同痴呆组和卒中非痴呆组之间存在差异(单因素方差分析F=6.69，p=0.001和Bonferroni p=0.01)，未发生痴呆组的VGLUT1平均值最高。结论：VAD和阿尔茨海默病的特征之一是谷氨酸能突触丢失，但在卒中后额叶皮质对颞叶皮质的突触，尤其是谷氨酸能突触的保留，在维持认知和预防痴呆方面起着重要作用。神经病学(R)2010；75：1803-1809
Objectives: Vascular dementia (VaD) accounts for approximately 15%-20% of all dementias, but the relationship of progressive cognitive impairment to neurochemical changes is poorly understood. We have therefore investigated glutamatergic synaptic markers in VaD.Methods: We used homogenates prepared from gray matter from 2 neocortical regions (Brodmann area [BA] 9 and BA 20) and Western blotting to determine the concentrations of key components of the glutamatergic neurotransmitter system, vesicular glutamate transporter 1 (VGLUT1) and excitatory amino acid transporter EAAT2 (GLT-1), and the ubiquitous synaptic protein, synaptophysin, in 73 individuals-48 patients with cerebrovascular disease with and without dementia, 10 patients with AD, and 15 controls-in a case-control design.Results: VGLUT1 concentrations in BA 20 and BA 9 were correlated with CAMCOG total (Rs 0.525, p = 0.018, n = 20; Rs 0.560, p = 0.002, n = 27) and CAMCOG memory scores (Rs 0.616, p = 0.004, n = 20; Rs 0.675, p = 0.000, n = 27). VGLUT1 concentration in BA 9 differed between the different dementia groups and the stroke no dementia group (1-way analysis of variance F = 6.69, p = 0.001 and Bonferroni p = 0.01 in each case), with subjects with stroke who did not develop dementia exhibiting the highest mean value for VGLUT1.Conclusions: These data suggest that loss of glutamatergic synapses is a feature of VaD and Alzheimer disease but the preservation of synapses, in particular glutamatergic synapses, in the frontal cortex against the temporal cortex plays a role in sustaining cognition and protecting against dementia following a stroke. Neurology (R) 2010;75:1803-1809