Department of Pharmacology and Systems Therapeutics, The Mount Sinai School of Medicine, New York City, NY 10075-0361, USA.
J Hum Genet. 2009 Nov;54(11):665-75. doi: 10.1038/jhg.2009.93. Epub 2009 Oct 16.
The prefrontal cortex has been implicated in schizophrenia (SZ) and affective disorders by gene expression studies. Owing to reciprocal connectivity, the thalamic nuclei and their cortical fields act as functional units. Altered thalamic gene expression would be expected to occur in association with cortical dysfunction. We screened the expression of the entire human genome of neurons harvested by laser-capture microdissection (LCM) from the thalamic primary relay to dorsolateral prefrontal cortex in three psychiatric disease states as compared with controls. Microarray analysis of gene expression showed the largest number of dysregulated genes was in SZ, followed by major depression (MD) and bipolar mood bipolar (BP) (1152, 385 and 288, respectively). Significantly, IGF1-mTOR-, AKT-, RAS-, VEGF-, Wnt- and immune-related signaling, eIF2- and proteasome-related genes were unique to SZ. Vitamin D receptor and calcium signaling pathway were unique to BP. AKAP95 pathway and pantothenate and CoA biosynthesis were unique to MD. There are significant differences among the three psychiatric disorders in MDNp cells. These findings offer new insights into the transcriptional dysregulation in the thalamus of SZ/BP/MD subjects.
前额叶皮层的基因表达研究表明其与精神分裂症（SZ）和情感障碍有关。由于相互连接，丘脑核及其皮质场作为功能单元起作用。皮质功能障碍时，预计会出现丘脑基因表达的改变。我们通过激光捕获显微切割（LCM）从丘脑初级中继到背外侧前额叶皮层中采集神经元，与对照组相比，在三种精神疾病状态下筛选了整个人类基因组的表达。基因表达的微阵列分析显示，失调基因数量最多的是 SZ，其次是重度抑郁症（MD）和双相情感障碍（BP）（分别为 1152、385 和 288）。值得注意的是，IGF1-mTOR、AKT、RAS、VEGF、Wnt 和免疫相关信号、eIF2 和蛋白酶体相关基因是 SZ 所特有的。维生素 D 受体和钙信号通路是 BP 所特有的。AKAP95 通路和泛酸和辅酶 A 生物合成是 MD 所特有的。MDNp 细胞在三种精神障碍之间存在显著差异。这些发现为 SZ/BP/MD 受试者的丘脑转录失调提供了新的见解。
