| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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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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