Summary of Research Project Results Under the JSPS FY2000
"Research for the future Program"



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.

7.Projetct Leader
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

[Reference Articles]
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

Author Title of Article
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


back