Monitoring neurodegeneration in diabetes using adult neural stem cells derived from the olfactory bulb.

Introduction: Neurons have the intrinsic capacity to produce insulin, similar to pancreatic cells. Adult neural stem cells (NSCs), which give rise to functional neurons, can be established and cultured not only by intracerebral collection, which requires difficult surgery, but also by collection from the olfactory bulb (OB), which is relatively easy. Adult neurogenesis in the hippocampus (HPC) is significantly decreased in diabetes patients.

Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb.

In the present study, we demonstrated that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from the hippocampus and olfactory bulb (OB). Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampal and OB-derived neural stem cells. Our analysis indicated that the balance between Wnt3, which triggers the expression of insulin via NeuroD1, and IGFBP-4, which inhibits the original Wnt3 action, is regulated depending on diabetic (DB) status.

Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis.

The mammalian brain contains neural stem cells (NSCs) that enable continued neurogenesis throughout adulthood. However, NSC function and/or numbers decline with increasing age. Adult hippocampal neurogenesis is unique in that astrocytes secreting Wnt3 promote NSC differentiation in a paracrine manner.