NF-κB signaling pathway inhibition suppresses hippocampal neuronal apoptosis and cognitive impairment via RCAN1 in neonatal rats with hypoxic-ischemic brain damage.

Autor: Fang H; a Department of Anesthesiology , Guizhou Provincial People's Hospital , Guiyang , P. R. China.; b Department of Anesthesiology , Guizhou University People's Hospital, , Guiyang, P. R. China., Li HF; c Department of Anesthesiology, West China Second University Hospital , Sichuan University , Chengdu , P. R. China., Yang M; a Department of Anesthesiology , Guizhou Provincial People's Hospital , Guiyang , P. R. China.; b Department of Anesthesiology , Guizhou University People's Hospital, , Guiyang, P. R. China., Liao R; d Department of Anesthesiology, West China Hospital , Sichuan University , Chengdu , P. R. China., Wang RR; d Department of Anesthesiology, West China Hospital , Sichuan University , Chengdu , P. R. China., Wang QY; d Department of Anesthesiology, West China Hospital , Sichuan University , Chengdu , P. R. China., Zheng PC; e Guizhou University Research Center for Analysis of Drugs and Metabolites , Guizhou University , Chengdu , P. R. China., Zhang FX; a Department of Anesthesiology , Guizhou Provincial People's Hospital , Guiyang , P. R. China.; b Department of Anesthesiology , Guizhou University People's Hospital, , Guiyang, P. R. China., Zhang JP; a Department of Anesthesiology , Guizhou Provincial People's Hospital , Guiyang , P. R. China.; b Department of Anesthesiology , Guizhou University People's Hospital, , Guiyang, P. R. China.
Jazyk: angličtina
Zdroj: Cell cycle (Georgetown, Tex.) [Cell Cycle] 2019 May; Vol. 18 (9), pp. 1001-1018. Date of Electronic Publication: 2019 May 03.
DOI: 10.1080/15384101.2019.1608128
Abstrakt: NF-κB 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-κB and RCAN1 in HIBD remains unclear. This study aimed to explore the mechanism of NF-κB 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-κB signaling pathway in HIBD. Then, the learning and memory ability of rats was evaluated. Expression of RCAN1, NF-κB signaling pathway-related genes and glial fibrillary acidic protein (GFAP), S-100β and acetylcholine (Ach) level, and acetylcholinesterase (AchE) activity were determined with neuron apoptosis detected to further explore the function of NF-κB signaling pathway. RCAN1 could influence the development of HIBD. In the HIBD model, the expression of RCAN1 and NF-κB-related genes increased, and NF-κB p65 showed a significant nuclear shift. By activation of NF-κB or overexpression of RCAN1, the number of neuronal apoptosis, S-100β protein level, and AchE level increased significantly, Ach activity decreased significantly, and GFAP positive cells increased. In addition, after the activation of NF-κB or overexpression of RCAN1, the learning and memory ability of HIBD rats was inhibited. All the results show that activation of NF-κB signaling pathway promotes RCAN1 expression, thus increasing neuronal apoptosis and aggravating cognitive impairment in HIBD rats.
Databáze: MEDLINE