Next-Generation sequencing of the hippocampus transcriptome in aged and cognitive impaired rats

The current study employed next generation RNA sequencing using two different platforms (Illumina and Ion Proton) to examine gene expression differences related to brain aging, cognitive decline, and hippocampus subregions (CA1, CA3, DG). Young and aged rats were trained on a spatial episodic memory task. The results describe regional differences in gene expression and point to regional differences in vulnerability to aging. Aging was associated with increased expression of immune response related genes, particularly in the dentate gyrus. For the memory task, impaired performance of aged animals was linked to the regulation of Ca2+ and synaptic function in region CA1. Finally, we provided a transcriptomic characterization of the three subregions regardless of age or cognitive status, highlighting and confirming a correspondence between cytoarchitectural boundaries and molecular profiling.本研究采用两种不同平台（Illumina与Ion Proton）的下一代RNA测序技术，探究与脑衰老、认知衰退以及海马亚区（CA1、CA3、DG）相关的基因表达差异。实验对幼年与老年大鼠开展空间情景记忆任务训练。研究结果揭示了基因表达的脑区差异，并指出不同脑区对衰老的易感性存在区别。衰老与免疫应答相关基因的表达上调显著相关，该现象在齿状回（DG）中尤为显著。在记忆任务中，老年动物的行为表现受损与CA1脑区的钙离子（Ca²+）及突触功能调控异常密切相关。最后，本研究对三个海马亚区进行了转录组学特征表征，分析未受样本年龄与认知状态的影响，明确验证了细胞构筑边界与分子谱之间的对应关系。