Fang_2019_Cell.Cycle_18_1001

NF-kappaB is a core transcription factor, the activation of which can lead to hypoxic-ischemic brain damage (HIBD), while RCAN1 plays a protective role in HIBD. However, the relationship between NF-kappaB and RCAN1 in HIBD remains unclear. This study aimed to explore the mechanism of NF-kappaB signaling pathway in hippocampal neuron apoptosis and cognitive impairment of neonatal rats with HIBD in relation to RCAN1. Initially, microarray analysis was used to determine the differentially expressed genes related to HIBD. After the establishment of HIBD rat models, gain- or loss-of-function assay was performed to explore the functional role of NF-kappaB signaling pathway in HIBD. Then, the learning and memory ability of rats was evaluated. Expression of RCAN1, NF-kappaB signaling pathway-related genes and glial fibrillary acidic protein (GFAP), S-100beta and acetylcholine (Ach) level, and acetylcholinesterase (AchE) activity were determined with neuron apoptosis detected to further explore the function of NF-kappaB signaling pathway. RCAN1 could influence the development of HIBD. In the HIBD model, the expression of RCAN1 and NF-kappaB-related genes increased, and NF-kappaB p65 showed a significant nuclear shift. By activation of NF-kappaB or overexpression of RCAN1, the number of neuronal apoptosis, S-100beta protein level, and AchE level increased significantly, Ach activity decreased significantly, and GFAP positive cells increased. In addition, after the activation of NF-kappaB or overexpression of RCAN1, the learning and memory ability of HIBD rats was inhibited. All the results show that activation of NF-kappaB signaling pathway promotes RCAN1 expression, thus increasing neuronal apoptosis and aggravating cognitive impairment in HIBD rats.