Antidepressant effect of stem cell-derived monoaminergic grafts.
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.
Cunningham
Miles G
MG
Laboratory for Neural Reconstruction, McLean Hospital, Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. mcunningham@mclean.harvard.edu
Donalds
Rachael A
RA
Carlezon
William A
WA
Hong
Sunghoi
S
Kim
Dae-Sung
DS
Kim
Dong-Wook
DW
Kim
Kwang-Soo
KS
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015283:Citalopram / Q000494:pharmacology; D003866:Depressive Disorder / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000637:transplantation*; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D018687:Antidepressive Agents, Second-Generation; D015306:Biogenic Monoamines; D050483:Dopamine Plasma Membrane Transport Proteins; D016760:Proto-Oncogene Proteins c-fos; D015283:Citalopram; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine