Abnormal expression of glutamate transporters in temporal lobe areas in elderly patients with schizophrenia.
Abnormal expression of glutamate transporters in temporal lobe areas in elderly patients with schizophrenia.
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DOI：
10.1016/j.schres.2012.12.019
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发表时间：
2013-03
影响因子：
4.5
通讯作者：
McCullumsmith RE
中科院分区：
文献类型：
--
作者：
Shan D;Lucas EK;Drummond JB;Haroutunian V;Meador-Woodruff JH;McCullumsmith RE
谷氨酸转运体促进谷氨酸的缓冲、清除和循环，并在维持突触和突触外谷氨酸水平方面发挥重要作用。谷氨酸转运蛋白表达的改变可能导致谷氨酸神经传递异常，参与精神分裂症的病理生理。此外，颞上回和海马体结构的改变与这种疾病有关，这表明这些区域的突触可能是在一生的严重精神疾病和抗精神病药物治疗中重塑的。因此，我们假设精神分裂症患者的颞上回和海马的谷氨酸神经传递可能异常。为了验证这一假设，我们检测了精神分裂症患者（n = 23）和对照组（n = 27）中兴奋性氨基酸转运蛋白1-3和泡状谷氨酸转运蛋白1和2的蛋白表达。我们发现精神分裂症患者颞上回EAAT1和EAAT2蛋白表达减少，海马EAAT2蛋白表达减少。我们未发现神经元转运体EAAT3或突触前泡状谷氨酸转运体VGLUT1-2的表达有任何变化。此外，我们未检测到抗精神病药物对氟哌啶醇治疗9个月大鼠颞叶关联皮层或海马中EAAT1和EAAT2蛋白表达的影响。我们的研究结果表明，在精神分裂症患者的颞叶谷氨酸突触中，谷氨酸的缓冲和再摄取，而不是突触前释放发生了改变。
Glutamate transporters facilitate the buffering, clearance and cycling of glutmate and play an important role in maintaining synaptic and extrasynaptic glutamate levels. Alterations in glutamate transporter expression may lead to abnormal glutamate neurotransmission contributing to the pathophysiology of schizophrenia. In addition, alterations in the architecture of the superior temporal gyrus and hippocampus have been implicated in this illness, suggesting that synapses in these regions may be remodeled from a lifetime of severe mental illness and antipsychotic treatment. Thus, we hypothesize that glutamate neurotransmission may be abnormal in the superior temporal gyrus and hippocampus in schizophrenia. To test this hypothesis, we examined protein expression of excitatory amino acid transporter 1-3 and vesicular glutamate transporter 1 and 2 in subjects with schizophrenia (n = 23) and a comparison group (n = 27). We found decreased expression of EAAT1 and EAAT2 protein in the superior temporal gyrus, and decreased EAAT2 protein in the hippocampus in schizophrenia. We didn’t find any changes in expression of the neuronal transporter EAAT3 or the presynaptic vesicular glutamate transporters VGLUT1-2. In addition, we did not detect an effect of antipsychotic medication on expression of EAAT1 and EAAT2 proteins in the temporal association cortex or hippocampus in rats treated with haloperidol for 9 months. Our findings suggest that buffering and reuptake, but not presynaptic release, of glutamate is altered in glutamate synapses in the temporal lobe in schizophrenia.
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影响因子：
4.5
作者：
Bauer, Deborah;Haroutunian, Vahram;Meador-Woodruff, James H.;McCullumsmith, Robert E.
通讯作者：
McCullumsmith, Robert E.
DOI：
10.2174/1874440001206010026
发表时间：
2012
期刊：
The open neuroimaging journal
影响因子：
--
作者：
Fujimoto T;Okumura E;Takeuchi K;Kodabashi A;Tanaka H;Otsubo T;Nakamura K;Sekine M;Kamiya S;Higashi Y;Tsuji M;Shimooki S;Tamura T
通讯作者：
Tamura T
影响因子：
11
作者：
Eastwood, SL;Harrison, PJ
通讯作者：
Harrison, PJ
影响因子：
--
作者：
Bruder, G;Kayser, J;Gorman, J
通讯作者：
Gorman, J
影响因子：
4.5
作者：
Eastwood, SL;Harrison, PJ
通讯作者：
Harrison, PJ