| 1.Research Institution | Niigata University | |
| 2.Research Area | Life Science | |
| 3.Research Field | Higher Brain Function | |
| 4.Term of Project | FY1996〜FY2000 | |
| 5.Project Number | 96L00203 | |
| 6.Title of Project | Growth Factor Regulation of Synaptic Development and Its Function in the Brain. |
| Name | Institution,Department | Title of Position |
| Nawa, Hiroyuki | Niigata University, Brain Research Inst. | Professor |
8.Core Members
| Names | Institution,Department | Title of Position |
| Niigata University, Brain Research Inst. | Professor | Associate Prof. |
| Niigata University, Brain Research Inst. | Professor | Assistant Prof. |
| Niigata University, Brain Research Inst. | Professor | Assistant Prof. |
9.Cooperating Researchers
| Names | Institution,Department | Title of Position |
| Niigata University, Brain Research Inst. | Professor | Technical Scientist |
| Niigata University, Brain Research Inst. | Professor | Research Scientist |
| Niigata University, Brain Research Inst. | Professor | Technical Associate |
10.Summary of Research Results
|
○Among various growth factors, neurotrophins exert the potent activity to enhance neuronal translation. This process involves the activation of translation initiation step that is regulated by 4EBP phosphorylation. ○Epidermal growth factor (EGF) and interleukin can counteract against the neurotrophic activity of neurotrophins to suppress the expression of glutamate receptors and transmitters in cultured immature neurons. ○BDNF can enhance the expression of AMPA-type glutamate receptors, which involves two molecular processes: 1) BDNF induces the interaction between AMPA receptor subunit GluR2/3 and NSF to translocate itself to cell surfaces. 2) Postsynaptic proteins including various PDZ molecules, whose levels are increased by BDNF in parallel, stabilize the AMPA receptors on synaptic surfaces. ○Using two-site enzyme immunoassay, we measured the protein levels of the growth factors, EGF as well as BDNF, in the postmortem samples of schizophrenic patients and control subjects. BDNF levels are increased in the limbic system whereas EGF are decreased in the forebrain regions. ○Rats that have been treated with the above growth factors during development exhibits abnormality in various behavioral tests including acoustic startle response and social interaction. These animal results confirm that these protein factors indeed contribute to human psychosis. |
11.Key Words
(1)BDNF、(2)Neurotrophin、(3)EGF
(4)Cytokine、(5)Brain、(6)PCP
(7)Amphetamine、(8)Psychosis、(9)Behavior
12.References
| Author | Title of Article | |||
| Suzuki, T., et al. | Biochemical evidence for localization of AMPA-type glutamate receptor subunits in the dendritic raft. | |||
| Journal | Volume | Year | Pages Concerned | |
| Mol. Brain Res. In press. | ||||
| Author | Title of Article | |||
| Weidong, Li., et al. | Characterization of a novelsynGAP isoform, synGAP-beta. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem, in press. | ||||
| Author | Title of Article | |||
| Watakabe, A., et al. | Similarity and Variation in Gene Expression Among Human Cerebral Cortical Subregions Revealed By DNAMacroarrays DNA Macroarrays: Technical Consideration of RNA Expression Profiling from Postmortem Samples | |||
| Journal | Volume | Year | Pages Concerned | |
| Mol. Brain Res. In press. | ||||
| Author | Title of Article | |||
| Nawa, H., et al. | Cytokine and growth factor involvement in schizophrenia--support for the developmental model. | |||
| Journal | Volume | Year | Pages Concerned | |
| Mol. Psychiatry | 5 | 2000 | 594-603 | |
| Author | Title of Article | |||
| Mizuno, M., et al. | Involvement of brain-derivedneurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Neurosci | 20 | 2000 | 7116-7121 | |
| Author | Title of Article | |||
| Takahashi, M., et al. | Abnormal expression of brain-derivedneurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. | |||
| Journal | Volume | Year | Pages Concerned | |
| Mol. Psychiatry | 2000 | 293-300 | ||
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| Yamaguchi, T., et al. | Molecular Characterization of a Novel Gamma Glutamyl Transpeptidase Homologue Found in Rat Brain | |||
| Journal | Volume | Year | Pages Concerned | |
| J Biochem. | 128 | 2000 | 101-106 | |
| Author | Title of Article | |||
| Linden, A. M., et al. | Expression of neurotrophins BDNF and NT-3, and their receptors in rat brain After administration of antipsychotic and psychotrophic agents. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Mol. Neurosci. | 14 | 2000 | 27-37 | |
| Author | Title of Article | |||
| Iritani, S., et al. | The distribution of neuropeptide Y and brain-derived neurotrophic factor immunoreactivity in hippocampal formation of the monkey and rat. | |||
| Journal | Volume | Year | Pages Concerned | |
| Brain Res. | 852 | 2000 | 475-478 | |
| Author | Title of Article | |||
| Han, D., et al. | Involvement of nitric oxide inpentylenetetrazole-induced kindling in rats. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Neurochem. | 74 | 2000 | 792-798 | |