To gain insight into the potential protective mechanisms of low phenylalanine diet (LPD) in phenylketonuria (PKU), gene expression profiles were studied in the cerebral cortex and hippocampus of a PKU mouse model (BTBR-Pah^enu2). PKU mice were fed with low Phe diet (LPD-PKU group) and normal diet (PKU group). Wild-type mice were treated with normal diet (WT group) as control. After 12 weeks, we detected gene expression in the cerebral cortex and hippocampus of the three groups by RNA-sequencing, and then screened the differentially-expressed genes (DEGs) among the groups by bioinformatics analyses. We found that the transcriptional profiles of both cerebral cortex and hippocampus changed markedly between PKU and WT mice. Furthermore, LPD changed the transcriptional profiles of the cerebral cortex and the hippocampus of PKU mice significantly, especially in the cerebral cortex, with overlaps of genes that changed with the disease and altered by LPD treatment. In the cerebral cortex, hundreds of DEGs enriched in a wide spectrum of biological processes, molecular function, and cellular component, including nervous system development, axon development and guidance, calcium ion binding, modulation of chemical synaptic transmission, and regulation of protein kinase activity. In the hippocampus, the overlapping genes were enriched in positive regulation of long term synaptic, negative regulation of excitatory postsynaptic potential, positive regulation of synapse assembly. Our results showed that genes impaired in PKU and then rescued by LPD might indicate the potential protective capability of LPD in the PKU brain.

为了深入了解低苯丙氨酸饮食 (LPD) 在苯丙酮尿症 (PKU) 中的潜在保护机制，我们在 PKU 小鼠模型 (BTBR- Pah ^{enu2 ) 的大脑皮层和海马中研究了基因表达谱}）。PKU小鼠喂食低Phe饮食（LPD-PKU组）和正常饮食（PKU组）。野生型小鼠用正常饮食（WT组）作为对照。12周后，我们通过RNA测序检测了三组大脑皮层和海马中的基因表达，然后通过生物信息学分析筛选了各组之间的差异表达基因（DEGs）。我们发现大脑皮层和海马的转录谱在 PKU 和 WT 小鼠之间发生了显着变化。此外，LPD 显着改变了 PKU 小鼠大脑皮层和海马的转录谱，特别是在大脑皮层中，基因的重叠随疾病发生变化，并因 LPD 治疗而改变。在大脑皮层中，数百个 DEG 富含广泛的生物过程、分子功能、和细胞成分，包括神经系统发育、轴突发育和引导、钙离子结合、化学突触传递的调节和蛋白激酶活性的调节。在海马区，重叠基因富集长时程突触正调控、兴奋性突触后电位负调控、突触组装正调控。我们的研究结果表明，在 PKU 中受损的基因然后被 LPD 拯救可能表明 LPD 在 PKU 大脑中的潜在保护能力。兴奋性突触后电位负调节，突触组装正调节。我们的研究结果表明，在 PKU 中受损的基因然后被 LPD 拯救可能表明 LPD 在 PKU 大脑中的潜在保护能力。兴奋性突触后电位负调节，突触组装正调节。我们的研究结果表明，在 PKU 中受损的基因然后被 LPD 拯救可能表明 LPD 在 PKU 大脑中的潜在保护能力。