POS-792 OMEGA-3 ATTENUATES UREMIA-INDUCED BRAIN DAMAGE IN MICE

Abstract

Although the cause of central nervous system (CNS) disorder in patients with CKD has not been completely identified yet, recent papers have attributed accumulated uremic toxin to be its main cause. Additionally, omega-3 polyunsaturated fatty acid (ω3-PUFA) is abundant in the nervous system and plays an important role in maintaining normal nerve function. The objective of this study is to identify brain damage caused by uremic toxicity and determine the protective effects of ω-3 PUFA against uremic toxin. We divided the mice into the following groups: wild-type (wt) sham (n = 8), ω-3 PUFA sham (n=8), Fat-1 sham (n = 8), ischemia-reperfusion (IR) (n = 20), and ω-3 PUFA+IR (n=20) Fat-1+IR (n = 20). Brain tissue, kidney tissue, and blood were collected three days after the operation of mice (sham and IR operation). We evaluated renal function and kidney histology of renal injury. To investigate neuronal cell death and how ω-3 PUFA affects brain injury, we evaluated brain histology and apoptotic protein expression. Ki67 and neuronal nuclei (NeuN) decreased in the brain of uremic mice as compared to wt mice brain. The protein expressions of Bax, cleaved caspase-3, and PARP were increased, whereas protein of Bcl2 decreased. Additionally, Ki67 and NeuN were increased in the ω-3 PUFA–treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. The protein expression of Bax, cleaved caspase-3, and PARP decreased, whereas the proteins of Bad and Bcl2 increased. Furthermore, the ω-3 PUFA–treated uremic mice and brain of uremic Fat-1 mice protein expression of p-PI3K, p-PDK1, and p-Akt were increased as compared to the brain of uremic mice. These results indicate that ω-3 PUFA show the protective effect in brain through PI(3)K-Akt signaling. Uremic toxin damages the brain and causes cell death. ω-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.