2010 Fiscal Year Final Research Report
Elucidation of the molecular mechanisms and physiological significance of the structural stabilization of neural networks by neurotrophins
| Project/Area Number |
21700384
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Fujita Health University |
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Principal Investigator |
OHIRA Koji Fujita Health University, 総合医科学研究所, 講師 (80402832)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 脳由来神経栄養因子(BDNF) / TrkB / レンチウイルスベクター / RNAi / 神経回路 / 大脳皮質 / 神経可塑性 / 細胞形態 |
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| Research Abstract |
The aim of this present study is the clarification of the molecular mechanisms and physiological significance of the stabilization of neural networks by analyzing the subtypes of brain-derived neurotrophic factor (BDNF) receptor TrkB. To achieve this purpose, first of all, I made the lentivirus vectors which expressed siRNAs of TrkB subtypes that were able to interfere with the expression of TrkB subtypes. In addition, the anti-T1 antibody was made to detect whether the knockdown of T1 at the protein level occurred, and I obtained an excellent antibody for T1.
Next, to establish an injection method of the lentivirus vectors into the cerebral ventricles of the fetals, I performed injections of the vectors at various conditions. However, the developments of the embryos after the injection have not advanced well. On the other hand, when the neocortical neurons at P7 or the primary cultures of neocortical neurons were infected with the vectors, I found that the dendritic processes of neurons infected with T1 siRNA virus vectors became long and the number of the branching points of neuronal processes increased.
We have clarified that GABAergic neurons are generated from layer 1 inhibitory neuron progenitor cells (L1-INP cell) by ischemia (Ohira et al., Nature Neuroscience 2010). There are two TrkB receptor subtypes in the mammalian CNS. The full-length isoform TK+ is a typical tyrosine kinase receptor. In contrast, the truncated isoform T1 possesses the isoform specific 11 amino acids in the intracellular domain. Interestingly, T1 was expressed in almost all L1-INP cells, whereas the ratio of L1-INP cells expressing TK+ was low, suggesting that T1 plays a role in the proliferation and differentiation of L1-INP cells.
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[Journal Article] Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells.2010
Author(s)
Ohira K, Furuta T, Hioki H, Nakamura KC, Kuramoto E, Tanaka Y, Funatsu N, Shimizu K, Oishi T, Hayashi M, Miyakawa T, Kaneko T, Nakamura S.
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Journal Title
Nature Neuroscience 13
Pages: 173-179
Peer Reviewed
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