Pluripotent stem cells as a model to study oxygen metabolism in neurogenesis and neurodevelopmental disorders.

Reactive oxygen species (ROS) and oxygen (O2) have been implicated in neurogenesis and self-renewal of neural progenitor cells (NPCs). On the other hand, oxidative unbalance, either by an impairment of antioxidant defenses or by an intensified production of ROS, is increasingly related to risk factors of neurodevelopmental disorders, such as schizophrenia. In this scenario, human induced pluripotent stem cells (hiPSCs) emerged as an interesting platform for the study of cellular and molecular aspects of this mental disorder, by complementing other experimental models, with exclusive advantages such as the recapitulation of brain development.

Pituitary adenylate cyclase-activating polypeptide (PACAP) can act as determinant of the tyrosine hydroxylase phenotype of dopaminergic cells during retina development.

In the chick retina, dopaminergic cells are generated between embryonic days 3 and 7 (E3/E7). However, the expression of tyrosine hydroxylase (TH), the first enzyme in the catecholamine synthetic pathway, is only detected after E11/E12. During the interval comprising E7 to E12, signals conveyed by cAMP are important to determine the TH phenotype.