PREBIOTICS, PROBIOTICS OR SYNBIOTICS THERAPY RESTORES COGNITIVE DECLINE IN OBESE RATS

Abstract

Our previous studies demonstrated that chronic high-fat diet (HFD) consumption caused not only obese-insulin resistance, but also increased brain oxidative stress, brain mitochondrial dysfunction, synaptic dysplasticity, and the cognitive decline. Recent studies showed that either prebiotics or probiotics therapy reduced gut inflammation and improved glycemic control in obese mice. However, the effects of prebiotics, probiotics and synbiotics on brain oxidative stress, brain mitochondrial function, hippocampal synaptic plasticity and cognitive function in obese-insulin resistant model have not been investigated. The present study hypothesized that the administration of prebiotics, probiotics or synbiotics improves these brain function in obese-insulin resistant rats. Fourty-eight male Wistar rats (200–250 g) were received either normal diet (ND) or HFD for 24 weeks. At week 13, animals in each dietary groups were subdivided into 4 subgroups (n=6/subgroup) to receive either phosphate buffer saline as vehicle, prebiotics (xylooligosaccharide 10% in PBS), probiotics (Lactobacillus paracasei HII01) (dose: 10ˆ7 CFU /day) or synbiotics (combined prebiotics and probiotics) for additional 12 weeks. At the end of the treatment, cognitive function by Morris water maze test and insulin sensitivity by oral glucose tolerance test were determined in each rat. After sacrificed, brains were removed to investigate brain oxidative stress level, brain mitochondrial function, and hippocampal synaptic plasticity. We found that 24-week HFD consumption caused obese-insulin resistance, increased brain oxidative stress, brain mitochondrial dysfunction via increased ROS production, membrane depolarization and mitochondrial swelling, impaired hippocampal synaptic plasticity, and cognitive decline. Interestingly, prebiotics, probiotics or synbiotics shared similarly efficacy for improving insulin sensitivity, brain mitochondrial function, synaptic plasticity, and restoring cognitive function (Fig.1). Moreover, synbiotics was the best therapy in reducing brain oxidative stress. These findings suggest that prebiotics, probiotics or synbiotics prevents cognitive decline in obese-insulin resistant model via reducing brain oxidative stress, restoring brain mitochondrial function and improving synaptic plasticity. The effects of prebiotics, probiotics or synbiotics on brain function in obese-insulin resistant rats. Brain mitochondrial dysfunction as indicated by ROS production (A) and brain oxidative stress as indicated by brain MDA level (B) in HFV was attenuated in all treatment groups. Cognitive impairment in HFV was improved in all treatment groups as indicated by decreased time required to reach the platform (C) and increased time spent in the target quadrant (D). ND; rats fed with normal diet, NDV; ND-fed rats with PBS, NDPE; ND-fed rats with prebiotics, NDPO; ND-fed rats with probiotics, NDC; ND-fed rats with prebiotics and probiotics, HFD; rats fed with high fat diet, HFV; HFD-fed rats with PBS, HFPE; HF-fed rats with prebiotics, HFPO; HFD-fed rats with probiotics, HFC; HF-fed rats with prebiotics and probiotics (n=5–6 of each group). *p<0.05 in comparison with NDV, †p<0.05 in comparison with HFV.