Stem Cells in Neuroendocrinology

Abstract

Depression is a highly prevalent complex neuropsychiatric disorder, which ranks first among all mental and neurological disorders as a contributor to the global burden of disease. However, available treatments are still far from ideal, for their specificity as well as their efficacy. This situation can now be improved by the increasing availability of stem cells, which allows the development of in vitro human neural systems to model the brain. These models complement observations from animal models and patients with depression, allowing for a better understand-ing of the complexity of this psychiatric illness and potential treatments. Cells derived from the olfactory neuroepithelium, multipotent fetal hippocampal progen-itor cells (HPCs) and human induced pluripotent stem cells (iPSCs) have shown promising leads. Using HPCs and iPSC-derived forebrain neurons, we managed to provide further insights into the action of drugs with antidepressant action as well as on molecular mechanisms underlying the effect of stress and inflammation, both linked to the pathophysiology of depression. Particular attention has been paid to the complex pathways by which the immune and stress systems differently deter-mine the final developmental fate of HPCs and the synaptic plasticity of iPSCs. The combination of accessibility and validity of the available stem cells models will allow further work to increase our insights into the biology of depression and support the identification of novel therapeutic targets.