Neuroprotective effects of Lycium barbarum polysaccharides against rat hippocampal apoptosis induced by chronic intermittent hypoxia

Abstract

We have shown neuronal apoptosis in the hippocampus of rats exposed to chronic intermittent hypoxia mimicking severe conditions of obstructive sleep apnea (OSA) syndrome in patients [1]. Lycium barbarum polysaccharides (LBP), active biological ingredients of traditional Chinese herbal medicine Goji, have been shown to possess cytoprotective properties [2]. The aim of this study was to examine the protective effects of LBP against neuronal apoptosis in the hippocampus in a severe OSA rodent model. We hypothesized that oral administration of LBP ameliorates neuronal apoptosis in the rat hippocampus induced by chronic intermittent hypoxia. Adult SD rats were randomly divided into 4 experimental groups, namely: (i) normoxic control (Nx); (ii) Nx treated with LBP; hypoxic groups treated with either (iii) LBP or (iv) vehicle. The hypoxic groups were kept in a normobaric chamber with inspired oxygen alternating from 21 to 5 ± 0.5% oxygen per minute for 8 hr/day for 7 days, whereas Nx groups was maintained in room air for 7 days. LBP (1mg/kg) were orally fed to the rats 2 hours prior the daily hypoxic treatment. Rats were sacrificed and the hippocampus was harvested for measurements of oxidative marker, malondialdehyde (MDA), apoptotic cell death using TUNEL assay, protein expression levels of antioxidant enzymes, and inflammatory cytokines by Western blot. There were significantly more TUNEL positive –labeling cells in the CA regions and dentate gyrus of the hippocampus in the vehicle-treated hypoxic group than those of the Nx control and LBP-treated groups. In addition, levels of MDA and the protein expressions of cleaved caspase 3 and inflammatory cytokines were increased in the vehicle-treated hypoxic group when compared to the Nx groups and were lowered by the LBP treatment. Intriguingly, there were significantly more PCNA-labeling cells in the dentate gyrus of the hippocampus in the LBP-treated hypoxic groups than those of the other groups. Also, the protein expression of cyclin D1 was increased in the hypoxic groups when compared to the Nx groups. In conclusion, oral administration of LBP significantly ameliorates oxidative stress, inflammation and neuronal apoptosis with enhanced proliferative activities in the hippocampus of rats exposed to chronic intermittent hypoxia. Thus, LBP may be proposed as a health supplement to mitigate neurological deficits in OSA patients, for which awaits future studies to delineate the neuroprotective mechanism of LBP. [Studies supported by research grants (HKU 7510/06M, HKU 766110M) from RGC and funding (201007176007, SFPBR 200911159072) from HKU] [1] Hung, M.W., et al. (2008) J Pineal Res 44: 214-221. [2] Chang, R.C., et al. (2008). Cell Mol Neurobiol 28: 643-652.