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, Toshitaka Nabeshima

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalMolecular Psychiatry
Volume8
Issue number2
DOIs
Publication statusPublished - 24-03-2003

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Phosphatidylinositol 3-Kinase
Brain-Derived Neurotrophic Factor
Hippocampus
Protein-Tyrosine Kinases
Learning
trkB Receptor
Neuronal Plasticity
Spatial Memory
Long-Term Potentiation
Oligodeoxyribonucleotides
Oligonucleotides
Signal Transduction
Maintenance
Phosphorylation
Messenger RNA

All Science Journal Classification (ASJC) codes

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

Cite this

Mizuno, M. ; Yamada, K. ; Takei, N. ; Tran, M. H. ; He, J. ; Nakajima, A. ; Nawa, H. ; Nabeshima, Toshitaka. / Phosphatidylinositol 3-kinase : A molecule mediating BDNF-dependent spatial memory formation. In: Molecular Psychiatry. 2003 ; Vol. 8, No. 2. pp. 217-224.
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Mizuno, M, Yamada, K, Takei, N, Tran, MH, He, J, Nakajima, A, Nawa, H & Nabeshima, T 2003, 'Phosphatidylinositol 3-kinase: A molecule mediating BDNF-dependent spatial memory formation', Molecular Psychiatry, vol. 8, no. 2, pp. 217-224. https://doi.org/10.1038/sj.mp.4001215

Phosphatidylinositol 3-kinase : A molecule mediating BDNF-dependent spatial memory formation. / Mizuno, M.; Yamada, K.; Takei, N.; Tran, M. H.; He, J.; Nakajima, A.; Nawa, H.; Nabeshima, Toshitaka.

In: Molecular Psychiatry, Vol. 8, No. 2, 24.03.2003, p. 217-224.

Research output: Contribution to journalArticle

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AU - Mizuno, M.

AU - Yamada, K.

AU - Takei, N.

AU - Tran, M. H.

AU - He, J.

AU - Nakajima, A.

AU - Nawa, H.

AU - Nabeshima, Toshitaka

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Y1 - 2003/3/24

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