Phosphatidylinositol 3-kinase: A molecule mediating BDNF-dependent spatial memory formation

M. Mizuno, K. Yamada, N. Takei, M. H. Tran, J. He, A. Nakajima, H. Nawa, T. Nabeshima

研究成果: Article

125 引用 (Scopus)

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Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity such as long-term potentiation (LTP), a form of synaptic correlate of learning and memory. BDNF is also implicated in learning and memory. We have demonstrated that radial arm maze training in rats for spatial learning and memory results in a significant increase in the BDNF mRNA expression in the hippocampus. Moreover, antisense BDNF oligonucleotide treatment impaired not only acquisition, but also maintenance and/or recall of spatial memory in the maze. Although these results suggest a role of BDNF for spatial memory processes, the signal transduction mechanisms that mediate the actions of BDNF remain unknown. Here we show that phosphorylation of BDNF receptor tyrosine kinase B (TrkB), phosphatidylinositol 3-kinase (PI3-K) and Akt, a target of PI3-K, in the hippocampus increased in parallel with spatial memory formation. Moreover, an activation of translational processes was suggested in the hippocampus after the maze training. When spatial learning was inhibited by antisense BDNF oligodeoxynucleotide, the activation was diminished. Chronic treatment with PI3-K inhibitor wortmannin impaired spatial learning. Our findings suggested that activation of TrkB/PI3-K and protein synthesis signaling pathway by BDNF in the hippocampus is important for spatial memory.

元の言語English
ページ(範囲)217-224
ページ数8
ジャーナルMolecular Psychiatry
8
発行部数2
DOI
出版物ステータスPublished - 24-03-2003
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

これを引用

Mizuno, M., Yamada, K., Takei, N., Tran, M. H., He, J., Nakajima, A., Nawa, H., & Nabeshima, T. (2003). Phosphatidylinositol 3-kinase: A molecule mediating BDNF-dependent spatial memory formation. Molecular Psychiatry, 8(2), 217-224. https://doi.org/10.1038/sj.mp.4001215