Molecular & Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, United States.
J Psychiatr Res. 2013 Sep;47(9):1150-6. doi: 10.1016/j.jpsychires.2013.04.007. Epub 2013 May 24.
Glutamatergic therapies are emerging as the new path for the treatment of Major Depression Disorder. Recent reports reviewing the use of glutamate activity modulators in the treatment of resistant depression advocate the importance of understanding the alterations of the diverse components of this complex system in mood disorders. In this postmortem study we used in situ hybridization and microarray analysis to evaluate the gene expression of the membrane transporters SLC1A2 and SLCA3 and the vesicular transporter SLCA17A7 in the hippocampus of Major Depressive Disorder (MDD) and Bipolar Disorder (BPD) subjects. Samples from 8 controls, 11 MDD and 6 BPD subjects were processed for in situ hybridization using cRNA probes for SLC1A2, SLC1A3 and SLC17A7. Laser capture microdissection was used to collect tissue from adjacent sections for microarray analysis. The results showed that the expression of the membrane transporters SLC1A2 and SLC1A3 was diminished in the MDD group compared to controls. The expression of the vesicular glutamate transporter SLC17A7 on the other hand was increased in MDD subjects. As for the BPD group, all three transporters showed trends similar to those observed in MDD, but the changes observed did not reach significance. We hypothesize that the decreased expression of the membrane glutamate transporters and the increased expression of the vesicular transporter in the hippocampus would affect the balance of the glutamatergic circuitry of the hippocampus, and that this effect may be a major contributor to depressive symptoms.
谷氨酸能疗法正成为治疗重度抑郁症的新途径。最近的研究报告回顾了谷氨酸活性调节剂在治疗耐药性抑郁症中的应用，强调了理解情绪障碍中这个复杂系统的不同组成部分的改变的重要性。在这项尸检研究中，我们使用原位杂交和微阵列分析来评估海马体中重度抑郁症（MDD）和双相情感障碍（BPD）患者的膜转运体 SLC1A2 和 SLCA3 以及囊泡转运体 SLCA17A7 的基因表达。使用 SLC1A2、SLC1A3 和 SLC17A7 的 cRNA 探针对来自 8 名对照、11 名 MDD 和 6 名 BPD 患者的样本进行原位杂交。激光捕获微解剖用于收集相邻切片的组织进行微阵列分析。结果表明，与对照组相比，MDD 组的膜转运体 SLC1A2 和 SLC1A3 的表达减少。另一方面，MDD 患者中囊泡谷氨酸转运体 SLC17A7 的表达增加。对于 BPD 组，所有三种转运体的趋势与 MDD 中观察到的相似，但观察到的变化没有达到显著水平。我们假设海马体中膜谷氨酸转运体表达减少和囊泡转运体表达增加会影响海马体谷氨酸能回路的平衡，这种影响可能是抑郁症状的主要原因。
