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Antidepressant effect of stem cell-derived monoaminergic grafts

Cunningham, Miles G.a; Donalds, Rachael A.a; Carlezon, William A. Jrb; Hong, Sunghoic; Kim, Dae-Sungd; Kim, Dong-Wookd; Kim, Kwang-Sooc

doi: 10.1097/WNR.0b013e3282f0eb1c

In this study, we demonstrate that embryonic stem cells can be engineered to differentiate into high percentages of serotonergic and dopaminergic neurons. In vitro, these cells release serotonin and dopamine in response to membrane depolarization. Upon engraftment into the medial prefrontal cortex in rats, the homolog of the human anterior cingulate cortex, the cells assumed neuronal morphologies, expressed monoaminergic-specific proteins, and seemed to functionally integrate, as assessed by the upregulation of the immediate-early gene, cfos. Furthermore, the transplanted animals performed in a manner similar to that of animals that received the antidepressant, citalopram, when administered the forced swim test, a validated model of human depression. These results suggest that transplantation of customized stem cells might perhaps be useful in the study treatment of psychiatric disorders.

aLaboratory for Neural Reconstruction

bBehavioral Genetics Laboratory

cMolecular Neurobiology Laboratories, McLean Hospital, Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA

dBrain Korea 21 Project for Medical Sciences, Department of Physiology, Yonsei University College of Medicine, Seoul, Korea

Correspondence to Miles G. Cunningham, MRC 333, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA

Tel: +1 617 855 2051; fax: +1 617 855 3199; e-mail: and Dong-Wook Kim, PhD, Department of Physiology, Yonsei University College of Medicine, 134 Schinchon-dong, Seodaemun-gu, Seoul 120-752, Korea

Tel: +82 2 2228 1703; fax: +82 2 393 0203; e-mail:

Received 14 July 2007; accepted 8 August 2007

© 2007 Lippincott Williams & Wilkins, Inc.