Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling.
Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.
1 Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University , Seoul, South Korea .
Sung Min
SM
Nam
Jung Hoon
JH
Choi
Dae Young
DY
Yoo
Woosuk
W
Kim
Hyo Young
HY
Jung
Jong Whi
JW
Kim
Miyoung
M
Yoo
Sanghee
S
Lee
Chul Jung
CJ
Kim
Yeo Sung
YS
Yoon
In Koo
IK
Hwang
D000375:Aging / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D000089662:Doublecortin Protein; D005690:Galactose; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D055495:Neurogenesis / Q000187:drug effects*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction; D065852:Spatial Memory / Q000187:drug effects*; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D010936:Plant Extracts; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D003474:Curcumin; D005690:Galactose
CREB; Curcuma longa; D-galactose; brain-derived neurotrophic factor; subgranular zone