A genetic approach for the understanding of the brain micro-environment that regulates the plasticity of neural stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07116
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Keio University
• Principal Investigator: KANDA Hiroshi 慶應義塾大学, 医学部(信濃町), 講師 (60508597)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ショウジョウバエ / 神経幹細胞 / Neuroblast / 再活性化

Outline of Final Research Achievements

It has long been reported that adult neural stem cells (NSCs) possess significant plasticity. Interestingly, the plasticity of NSCs is also observed in lower organisms such as invertebrates. We have elucidated the molecular basis of how quiescent neural stem cells are reactivated by using powerful Drosophila genetics. We found that an evolutionarily conserved metabolic enzyme, whose function is required for the lipid metabolism, is required for the proper reactivation of NSCs. We found that this cell death is induced　by cholinergic neuron-dependent manner. In addition, the acetylcholine level was increased in the mutant animals. The inhibition of the degradation of acetylcholine also attenuated the reactivation of wild-type quiescent neural stem cells ex vivo.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

成体脳で行われるニューロンの新生は記憶の形成、ストレスからの回復、本能行動などに重要であると考えられており、これが抑制されることで抑鬱などの原因となる事が示唆されている。しかし、発生初期のニューロン新生を経て一旦分裂を休止した神経幹細胞が再活性化する分子機構はこれまでほとんど明らかにされていなかった。我々が本研究によって見出した知見は、上記の課題を解き明かす上で前衛的な知見となり得ると考えられる。