title: Stem cell therapy: a new approach to the treatment of refractory depression.
abstract: To better understand the relationship of repeated exposure to adversity during early development as a risk factor for refractory depression, we exposed pregnant female rats to ethanol and the resulting pups to corticosterone during adolescence. A stressful forced swim test was then used to induce depression-like behavior. The adolescent rat brains were examined for the possible therapeutic benefit of a combination of sertraline, an antidepressant, and neural stem cells (NSCs) complexed with atelocollagen in relation to the level of GABAergic interneuron and synaptic protein density in different brain regions. The combined exposures of prenatal and adolescent stress resulted in a reduction in parvalbumin (PV)-positive phenotype of GABAergic interneurons and reduced postsynaptic density protein 95 (PSD-95) levels in the anterior cingulate cortex, amygdala, and hippocampus. Treatments with sertraline and NSCs reversed the reductions in PV-positive cells and PSD-95 levels. Furthermore, the combined treatment of sertraline and NSCs resulted in reduced depressive-like behaviors. These experiments underscore a potentially important role for synaptic remodeling and GABAergic interneuron genesis in the treatment of refractory depression and highlight the therapeutic potential of stem cell and pharmacological combination treatments for refractory depression.
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 0608543, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Kigawa
authors.forename: Eri
authors.initials: E
authors.lastname: Hashimoto
authors.forename: Wataru
authors.initials: W
authors.lastname: Ukai
authors.forename: Takao
authors.initials: T
authors.lastname: Ishii
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuse
authors.forename: Hanako
authors.initials: H
authors.lastname: Tsujino
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shirasaka
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000503:physiopathology; D003131:Combined Modality Therapy; D061218:Depressive Disorder, Treatment-Resistant / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D059330:GABAergic Neurons / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D010320:Parvalbumins / Q000378:metabolism; D017208:Rats, Wistar; D020280:Sertraline / Q000494:pharmacology; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D000928:Antidepressive Agents; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010320:Parvalbumins; D020280:Sertraline