Poirier G L, Shires K L, Sugden D, Amin E, Thomas K L, Carter D A, Aggleton J P
School of Psychology, Cardiff University, Wales, UK.
Thalamus Relat Syst. 2008 Mar;4(1):59-77. doi: 10.1017/S1472928808000368.
Anterior thalamic lesions are thought to produce 'covert pathology' in retrosplenial cortex, but the causes are unknown. Microarray analyses tested the hypothesis that thalamic damage causes a chronic, hypo-function of metabolic and plasticity-related pathways (Experiment 1). Rats with unilateral, anterior thalamic lesions were exposed to a novel environment for 20 minutes, and granular retrosplenial tissue sampled from both hemispheres 30 minutes, 2h, or 8h later. Complementary statistical approaches (analyses of variance, predictive patterning and gene set enrichment analysis) revealed pervasive gene expression differences between retrosplenial cortex ipsilateral to the thalamic lesion and contralateral to the lesion. Selected gene differences were validated by QPCR, immunohistochemistry (Experiment 1), and in situ hybridisation (Experiment 2). Following thalamic lesions, the retrosplenial cortex undergoes profuse cellular transcriptome changes including lower relative levels of specific mRNAs involved in energy metabolism and neuronal plasticity. These changes in functional gene expression may be largely driven by decreases in the expression of multiple transcription factors, including brd8, c-fos, fra-2, klf5, nfix, nr4a1, smad3, smarcc2, and zfp9, with a much smaller number (nfat5, neuroD1, RXRγ) showing increases. These findings have implications for conditions such as diencephalic amnesia and Alzheimer's disease, where both anterior thalamic pathology and retrosplenial cortex hypometabolism are prominent.
丘脑前侧病变被认为会在压后皮质产生“隐匿性病理变化”，但其原因尚不清楚。基因芯片分析检验了丘脑损伤会导致代谢和可塑性相关通路出现慢性功能减退这一假说（实验1）。对患有单侧丘脑前侧病变的大鼠，使其暴露于新环境20分钟，然后在30分钟、2小时或8小时后从两侧半球采集颗粒状压后组织。互补性统计方法（方差分析、预测模式分析和基因集富集分析）显示，丘脑病变同侧与对侧的压后皮质之间存在普遍的基因表达差异。选定的基因差异通过定量聚合酶链反应、免疫组织化学（实验1）和原位杂交（实验2）进行了验证。丘脑病变后，压后皮质会发生大量细胞转录组变化，包括参与能量代谢和神经元可塑性的特定信使核糖核酸相对水平降低。这些功能基因表达的变化可能很大程度上是由多种转录因子表达下降驱动的，这些转录因子包括brd8、c-fos、fra-2、klf5、nfix、nr4a1、smad3、smarcc2和zfp9，只有少数（nfat5、neuroD1、RXRγ）表达增加。这些发现对诸如间脑失忆症和阿尔茨海默病等病症具有启示意义，在这些病症中，丘脑前侧病理变化和压后皮质代谢减退都很突出。
