title: Antidepressant effect of stem cell-derived monoaminergic grafts.
abstract: 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.
authors.affiliation: Laboratory for Neural Reconstruction, McLean Hospital, Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. mcunningham@mclean.harvard.edu
authors.forename: Miles G
authors.initials: MG
authors.lastname: Cunningham
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Donalds
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
authors.forename: Sunghoi
authors.initials: S
authors.lastname: Hong
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: 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
chemical_list: 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