Neuroprotective mechanism of lycium barbarum polysaccharides against rat hippocampal injuries in a rat model of obstructive sleep apnea

Abstract

Hippocampus is an important component of the central nervous system, which plays a crucial role in memory storage, cognitive function and mood regulation. Literatures reported that chronic intermittent hypoxia (CIH) mimicking clinical conditions of obstructive sleep apnea (OSA) cause hippocampal injury, which could be alleviated by administration of antioxidants. Upon CIH-induced insults, hippocampal regenerative mechanisms are subsequently initiated to repair the damages. Recently Lycium barbarum polysaccharides (LBP), bioactive ingredients of Wolfberry, received multitudinous attention as its antioxidant and anti-inflammatory properties hold great potential against the pathogenesis in different disease models. There were three hypotheses in this study namely: a) LBP could attenuate oxidative stress, inflammation and endoplasmic reticulum (ER) stress induced by CIH in the hippocampus. b) LBP could inhibit hippocampal cells death through mitigation of caspase-mediated intrinsic and extrinsic signaling cascades activated by oxidative stress and inflammation. c) LBP facilitated CIH-triggered regeneration through Akt pathway. Hippocampal injuries were induced in a CIH rat model simulating clinical features of pathogenesis in OSA patients. LBP pre-treatment significantly ameliorated oxidative stress by enhancing defensive antioxidant capacities, and by lowering the expression of inflammatory cytokines and mediators, and also ER stress-induced response. Additionally, LBP pre-treatment markedly abolished CIH-induced hippocampal cell death and reduced expressions of apoptotic molecules involved in intrinsic and extrinsic cascades. Besides, CIH induced hippocampal neurogenesis through BDNF/Akt/PCNA, JNK/c-Jun/cyclin D1 and PTEN/Akt/PCNA axis. LBP pre-treatment promoted CIH-induced regeneration through Akt/PCNA pathway. Most importantly, LBP pre-treatment significantly mitigated CIH-induced spatial memory deficits. In conclusion, LBP protected hippocampus by suppressing oxidative stress, inflammation, ER stress, apoptosis and promoting regenerative mechanism. Our results strongly suggested the prophylactic efficacy of LBP for attenuating the neurological deficits in OSA patients.