Jiang Yan, Wang Ajun, Zou Nian, Dai Huimin, Shan Ran, Ren Siyu, Jiang Tongcui, Li Nan
Anhui Medical University, Hefei, China.
Department of Neurosurgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Mol Biol Rep. 2025 Apr 10;52(1):382. doi: 10.1007/s11033-025-10483-6.
The development of the central nervous system (CNS) is essential for the growth of an organism. The unfolded protein response (UPR) plays an important role in the occurrence and progression of CNS. Hence, to identify the changing pattern of UPR signaling molecules and their related target molecules is extremely important. Immunohistochemical (IHC) analysis was conducted to assess the expression of NeuN, a neuronal marker, within the M1 region of the cerebral cortex of wild-type (WT) rats aged different weeks. The results showed a progressive increase in the expression of NeuN in correlation with the weekly age progression of the rats. Concurrently, in the CA3 region of the hippocampus and the S1Tr area of the cerebral cortex, the levels of UPR key molecules, GRP78 and XBP1s, exhibited an upward trend in accordance with the rats' weekly age. Western blot analysis revealed an inclination toward an increase in the expression of endoplasmic reticulum (ER) stress -associated key molecules, including GRP78, ATF6, XBP1, eIF-2α, CHOP and phosphorylated eIF-2α (p-eIF-2α). Additionally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) demonstrated a positive correlation between the expression of CHOP and the weekly age of the rats. These findings demonstrate that UPR signaling pathway has a certain pattern of change in the development of rat brain, suggesting that the UPR signaling pathway may play an important role in the development of the CNS, and suggesting that an applicability of XBP1s as a therapeutic candidate for childhood autism.
中枢神经系统（CNS）的发育对生物体的生长至关重要。未折叠蛋白反应（UPR）在CNS的发生和发展中起重要作用。因此，确定UPR信号分子及其相关靶分子的变化模式极为重要。进行免疫组织化学（IHC）分析以评估不同周龄野生型（WT）大鼠大脑皮质M1区域内神经元标志物NeuN的表达。结果显示，NeuN的表达随着大鼠周龄的增加而逐渐升高。同时，在海马体的CA3区域和大脑皮质的S1Tr区域，UPR关键分子GRP78和XBP1s的水平也随着大鼠周龄的增加呈上升趋势。蛋白质免疫印迹分析显示，内质网（ER）应激相关关键分子的表达有增加倾向，这些分子包括GRP78、ATF6、XBP1、eIF-2α、CHOP和磷酸化eIF-2α（p-eIF-2α）。此外，逆转录定量聚合酶链反应（RT-qPCR）表明CHOP的表达与大鼠周龄呈正相关。这些发现表明，UPR信号通路在大鼠大脑发育过程中有一定的变化模式，提示UPR信号通路可能在CNS发育中起重要作用，也提示XBP1s作为儿童自闭症治疗候选药物的适用性。
