Unraveling the crucial role of UPR pathway in rat brain development

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.