Zinc Regulation of Neural Stem Cell Proliferation and Antidepressant Efficacy

Changes in zinc homeostasis are strongly associated with abnormal brain function and a variety of neurological and neuropsychiatric disorders, including depression. It is hypothesized that the neurogenic potential of chronic antidepressant administration contributes to its therapeutic effects in depression. Thus, the goal of this work was to determine the extent to which zinc is needed for antidepressant drug induction of neural stem cell proliferation and differentiation. Human NTERA-2/D1 (NT2) cell culture, an established in vitro model system to study neuronal development, was utilized. Zinc deficiency impaired NT2 cell proliferation measured by the number of Ki67-positive cells. Treatment with fluoxetine or lithium did not result in a significant increase in cell proliferation rate. However, six-day treatment with these antidepressants had a stimulatory effect on NT2 cell differentiation revealed by immunofluorecent detection of the neuron-specific marker TuJ1. Furthermore, zinc deficient cultures treated with fluoxetine or lithium appeared to have a decreased expression of this neuronal marker. Taken together, these results suggest that the essential trace element zinc is needed for neuronal stem cell proliferation and differentiation.