Quercetin impairs learning and memory in normal mice via suppression of hippocampal phosphorylated cyclic AMP response element-binding protein expression.
Quercetin is a naturally occurring dietary flavonol and several reports have shown that quercetin substantially affects cognitive function in disease models, which suggests that quercetin might be a useful agent for treatment of memory dysfunction. However, only one report has examined the effects of quercetin on normal cognitive function. In the present study, we investigated the potential deleterious effects of quercetin on normal cognitive function using Western blot assays and the following behavioral tasks: passive avoidance, Y-maze, and Morris water maze. In the passive avoidance task, pre-acquisition administration of quercetin (10, 20, or 40 mg/kg, p.o.) caused significant cognitive impairments in mice (P < 0.05 or P < 0.01). Quercetin-treated groups (10, 20, or 40 mg/kg, p.o.) also showed significant memory impairments compared with the control group in the Y-maze task (P < 0.05). In the Morris water maze task, there were no significant differences among the groups during training trial sessions, but at the probe trial session, the quercetin-treated group (40 mg/kg, p.o.) spent significantly less time in the target quadrant than did the control group (P < 0.05). In Western blot assays of hippocampal tissue, we found that quercetin-treated groups showed decreased expression of phosphorylated Akt (pAkt), phosphorylated calcium-calmodulin kinase II (pCaMKII), and phosphorylated cyclic AMP response element-binding protein (pCREB). These results suggest that acute administration of quercetin impairs cognitive function by suppression of pAkt and pCaMKII, which, in turn, decreases pCREB expression in the hippocampus.
Jung
Won Yong
WY
Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
Park
Se Jin
SJ
Park
Dong Hyun
DH
Kim
Jong Min
JM
Kim
Dong Hyun
DH
Ryu
Jong Hoon
JH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000633:toxicity; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007858:Learning; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology / Q000633:toxicity*
D000975:Antioxidants; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D011794:Quercetin; D051057:Proto-Oncogene Proteins c-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2