Abstract
The blood-brain barrier (BBB) plays crucial roles for the maintenance of brain homeostasis. Recent findings demonstrate that BBB breakdown proceeds the onset of cognitive decline in dementia such as Alzheimer’s disease (AD). We have previously reported that coffee polyphenols (CPP) prevent cognitive dysfunction in APP/PS2 AD mouse model. However, the effects of CPP on age-related cognitive decline and BBB impairment remain unknown. In the present study, we investigated the effects of CPP diet for 8 months on age-related cognitive decline in senescence-accelerated mouse prone 8 (SAMP8) mice. Hippocampal BBB permeability was assessed by using Na-F dye. The protein expression of tight junctions (Claudin-5, Occludin) and synaptic markers (Synaptophysin, PSD-95) were measured by western blotting. BDNF concentration was examined by ELISA. The cognitive function was evaluated by novel object recognition test. Long-term ingestion of CPP significantly reduced BBB permeability and increased the Claudin-5 expression. Synaptic proteins and BDNF in hippocampus were also increased by CPP ingestion. Furthermore, significant positive correlations were observed between the expression of Claudin-5 and synaptic proteins, indicating that maintenance of BBB integrity by CPP might protects synaptic proteins. Moreover, the cognitive function was markedly improved by CPP treatment. These results suggest that long-term ingestion of CPP prevents age-related neuronal deficit and cognitive decline via maintenance of BBB integrity.
