Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.
Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.
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DOI：
10.1038/mp.2010.44
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发表时间：
2011-06
影响因子：
11
通讯作者：
中科院分区：
文献类型：
--
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一些研究已经提出脑谷氨酸信号传导异常和神经胶质病理学在重性抑郁症（MDD）的病因学中起作用。这些结论主要来自于对前脑脑区进行检查的死后研究。蓝斑是前脑广泛的去甲肾上腺素能神经支配的主要来源，因此对认知和情感功能发挥强大的调节作用，而认知和情感功能在MDD中失调。此外，改变的去甲肾上腺素能神经传递与抑郁症状相关，并被认为在MDD的病理生理学中发挥作用。在本研究中，我们使用激光捕获显微切割选择性收获蓝斑（LC）组织从死后的MDD患者，双相情感障碍（BPD）患者的大脑，并从精神正常的科目。利用微阵列技术，我们研究了基因表达的全球模式。选择候选基因的差异mRNA表达，然后使用实时定量PCR和原位杂交询问。我们的研究结果揭示了多种信号通路的改变，在LC的MDD，但不是BPD的主题。这些包括谷氨酸信号传导基因SLC1A2、SLC1A3、GLUL、生长因子基因FGFR 3和TrkB，以及仅在星形胶质细胞中表达的几个基因。我们的数据扩展了先前的研究结果，改变谷氨酸，星形胶质细胞和生长因子的功能，在MDD的第一次脑干。这些发现表明，这种改变：1）是MDD独有的，与BPD不同，2）影响多个脑区，表明这些功能的全脑失调。
Several studies have proposed that brain glutamate signaling abnormalities and glial pathology play a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from postmortem studies in which forebrain brain regions were examined. The locus coeruleus is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to play a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection to selectively harvest locus coeruleus (LC) tissue from postmortem brains of MDD patients, patients with bipolar disorder (BPD), and from psychiatrically-normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR and in situ hybridization. Our findings reveal multiple signaling pathway alterations in the LC of MDD, but not BPD subjects. These include glutamate signaling genes SLC1A2, SLC1A3, GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: 1) are unique to MDD and distinguishable from BPD, and 2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions.
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影响因子：
15.9
作者：
Giaume, C;McCarthy, KD
通讯作者：
McCarthy, KD
DOI：
10.1073/pnas.0406788101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Evans, SJ;Choudary, PV;Akil, H
通讯作者：
Akil, H
影响因子：
4.7
作者：
Karolewicz, B;Szebeni, K;Ordway, GA
通讯作者：
Ordway, GA
影响因子：
3.5
作者：
Figiel, Maciej;Allritz, Claudia;Engele, Juergen
通讯作者：
Engele, Juergen
影响因子：
3
作者：
Kerman, Ilan A.;Buck, Bradley J.;Watson, Stanley J.
通讯作者：
Watson, Stanley J.