Insulin Receptor Regulates Neurotrophin and Neurotrophin Receptor Expression in the Differentiation of Neural Stem Cells: <i>In Vitro</i> Study

Adult Neural stem cells (NSCs)/Neural Progenitor cells (NPCs) are known to play an important role in creating new neurons and glial cells. The self-renewal, multipotent abilities of NSCs are attributed to several of cell-intrinsic and extrinsic factors. Insulin is an important neuromodulator, particularly influencing neural survival, memory, and energy homeostasis. Insulin receptor is expressed in the adult NSC niche and also induces neurogenesis and gliogenesis and may be affected by neurotrophins. Neurotrophins have been demonstrated to play an active role in NSC differentiation into neurons and glial cells. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), both have significant roles in hippocampal plasticity and long-term potentiation events. However, the crosstalk between insulin and neurotrophic signaling pathways is still unclear and requires studies to understand brain development in insulin resistance conditions. Preliminary data from the current study suggest that insulin receptor is involved in regulating the transcript levels of neurotrophins (NGF, BDNF) and Trk receptors (TrkA, TrkB and p75NTR). It is also able to regulate the secretion of BDNF by neural stem cells. In addition, the data from the present study also reveal insulin receptor knockdown significantly altered the expression levels of key early brain cell type development markers such as PDGFR-α, GFAP, and Tuj1, which further confirms the essential role of crosstalk between insulin receptor and neurotrophins in brain development in regard to neural stem cell differentiation.