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J. Biol. Chem., Vol. 283, Issue 21, 14497-14505, May 23, 2008

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Curcumin Stimulates Proliferation of Embryonic Neural Progenitor Cells and Neurogenesis in the Adult Hippocampus^*

So Jung Kim, Tae Gen Son, Hee Ra Park, Mikyung Park, Min-Sun Kim, Hyung Sik Kim, Hae Young Chung, Mark P. Mattson, and Jaewon Lee¹

From the Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Korea and the Laboratory of Neurosciences, NIA, National Institutes of Health, Baltimore, Maryland 21224

Curcumin is a natural phenolic component of yellow curry spice, which is used in some cultures for the treatment of diseases associated with oxidative stress and inflammation. Curcumin has been reported to be capable of preventing the death of neurons in animal models of neurodegenerative disorders, but its possible effects on developmental and adult neuroplasticity are unknown. In the present study, we investigated the effects of curcumin on mouse multi-potent neural progenitor cells (NPC) and adult hippocampal neurogenesis. Curcumin exerted biphasic effects on cultured NPC; low concentrations stimulated cell proliferation, whereas high concentrations were cytotoxic. Curcumin activated extracellular signal-regulated kinases (ERKs) and p38 kinases, cellular signal transduction pathways known to be involved in the regulation of neuronal plasticity and stress responses. Inhibitors of ERKs and p38 kinases effectively blocked the mitogenic effect of curcumin in NPC. Administration of curcumin to adult mice resulted in a significant increase in the number of newly generated cells in the dentate gyrus of hippocampus, indicating that curcumin enhances adult hippocampal neurogenesis. Our findings suggest that curcumin can stimulate developmental and adult hippocampal neurogenesis, and a biological activity that may enhance neural plasticity and repair.

Received for publication, October 9, 2007 , and in revised form, March 17, 2008.

^* This work was authored, in whole or in part, by National Institutes of Health staff. This work was also supported by Grant No. R01-2005-000-10661-0 from the Basic Research Program of the Korea Science & Engineering Foundation and the Brain Korea 21 Project. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ To whom correspondence should be addressed: Dept. of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Korea. Tel.: 82-51-510-2805; Fax: 82-51-513-6754; E-mail: neuron{at}pusan.ac.kr.

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