Luteolin promotes long-term potentiation and improves cognitive functions in chronic cerebral hypoperfused rats.
Eur J Pharmacol. 2010 Feb 10;627(1-3):99-105. Epub 2009 Oct 24. PMID: 19857483
National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences&Peking Union Medical College, Beijing 100050, PR China.
Processes of synaptic plasticity, such as long-term potentiation (LTP), has been considered a cellular correlate of learning and memory and many neurological disorders accompanied by cognitive deficits exhibit abnormal synaptic function. This emerging concept is exemplified by Alzheimer's disease. Mounting evidence suggests that Alzheimer's disease begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, which make it critical to identify LTP enhancers to slow down or stop the progression of Alzheimer's disease. In this study, we found flavonoid luteolin could enhance basal synaptic transmission and facilitate the induction of LTP by high frequency stimulation in the dental gyrus of rat hippocampus. Furthermore, we investigated the effects of luteolin on chronic cerebral hypoperfusion-induced spatial learning dysfunction and LTP impairment in rat. The results showed chronic cerebral hypoperfusion produced by 2-vessel occlusion significantly impaired spatial learning and memory, and luteolin reversed the learning and memory deficit. 2-vessel occlusion resulted in dramatic inhibition of LTP formation in the hippocampus and luteolin significantly rescued the LTP impairment. These results demonstrate that luteolin not only directly modulates LTP formation, but also protects synapses from the detrimental effects of chronic cerebral hypoperfusion on LTP formation, which may contribute to the protective effects of luteolin on learning and memory. By immunoblotting, we found the effects of luteolin on LTP and memory may due to the activation of cAMP response element-binding protein (CREB). Therefore, flavonoid luteolin shows great potential as a novel treatment agent for protecting synaptic function and enhancing memory in neurodegenerative disorders.