Ianov Lara, Rani Asha, Beas Blanca S, Kumar Ashok, Foster Thomas C
Department of Neuroscience, McKnight Brain Institute, University of FloridaGainesville, FL, USA; Genetics and Genomics Program, Genetics Institute, University of FloridaGainesville, FL, USA.
Department of Neuroscience, McKnight Brain Institute, University of Florida Gainesville, FL, USA.
Front Aging Neurosci. 2016 May 17;8:113. doi: 10.3389/fnagi.2016.00113. eCollection 2016.
Cognitive function depends on transcription; however, there is little information linking altered gene expression to impaired prefrontal cortex function during aging. Young and aged F344 rats were characterized on attentional set shift and spatial memory tasks. Transcriptional differences associated with age and cognition were examined using RNA sequencing to construct transcriptomic profiles for the medial prefrontal cortex (mPFC), white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging. Age-related gene expression in the mPFC was similar to, though less robust than, changes in the dorsolateral PFC of aging humans suggesting that aging processes may be similar. Importantly, the pattern of transcription associated with aging did not predict cognitive decline. Rather, increased mPFC expression of genes involved in regulation of transcription, including transcription factors that regulate the strength of excitatory and inhibitory inputs, and neural activity-related immediate-early genes was observed in aged animals that exhibit delayed set shift behavior. The specificity of impairment on a mPFC-dependent task, associated with a particular mPFC transcriptional profile indicates that impaired executive function involves altered transcriptional regulation and neural activity/plasticity processes that are distinct from that described for impaired hippocampal function.
认知功能依赖于转录；然而，关于衰老过程中基因表达改变与前额叶皮质功能受损之间的联系，目前所知甚少。对年轻和老年F344大鼠进行注意力转换和空间记忆任务测试。利用RNA测序检查与年龄和认知相关的转录差异，以构建内侧前额叶皮质（mPFC）、白质和海马体CA1区的转录组图谱。结果表明不同区域对衰老的易感性存在差异。mPFC中与年龄相关的基因表达与衰老人类背外侧前额叶皮质的变化相似，尽管程度较弱，这表明衰老过程可能具有相似性。重要的是，与衰老相关的转录模式并不能预测认知能力下降。相反，在表现出延迟转换行为的老年动物中，观察到mPFC中参与转录调控的基因表达增加，这些基因包括调节兴奋性和抑制性输入强度的转录因子以及与神经活动相关的即早基因。在依赖mPFC的任务上出现的损伤特异性，与特定的mPFC转录图谱相关，这表明执行功能受损涉及转录调控以及神经活动/可塑性过程的改变，这些过程与海马体功能受损所描述的情况不同。
