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

Ryo Hidaka, Masanao Machida, Shin Fujimaki, Kazuyuki Terashima, Makoto Asashima, Tomoko Kuwabara

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. As a result, learning and memory functions, for which the HPC is responsible, decrease. METHODS: In the present study, we compared the effect of diabetes on neurogenesis and insulin expression in adult NSCs. Adult NSCs were derived from the HPC or OB of streptozotocin-induced diabetic rats. Comparative gene-expression analyses were carried out by using extracted tissues and established adult NSC cultures from the HPC or OB in diabetic rats. RESULTS: Diabetes progression influenced important genes that were required for insulin expression in both OB- and HPC-derived cells. Additionally, we found that the expression levels of several genes, such as voltage-gated sodium channels, glutamate transporters, and glutamate receptors, were significantly different in OB and HPC cells collected from diabetic rats. CONCLUSIONS: By using identified diabetes-response genes, OB NSCs from diabetes patients can be used during diabetes progression to monitor processes that cause neurodegeneration in the central nervous system (CNS). Because hippocampal NSCs and OB NSCs exhibited similar gene-expression profiles during diabetes progression, OB NSCs, which are more easily collected and established than HPC NSCs, may potentially be used for screening of effective drugs for neurodegenerative disorders that cause malignant damage to CNS functions.