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Molecular basis for the mind: nurturing the brain
Our research “from genes to mind” has progressed with various research tools such as mice lacking each of some neuropeptide receptors and PEPA, a specific new ligand of AMPA-type glutamate receptors. We have employed a wide range of research approaches including molecular biology, protein chemistry, electrophysiology and behavioral study. To achieve our goal, we also investigate learning and memory, neuron-glia interaction, synaptic transmission, etc.

Previously, we generated bombesin receptor knockout mice as well as neurotensin receptor knockout mice. We have shown that these mice are useful for understanding the molecular basis for behavior including social behavior, maternal behavior and stress responses.

PEPA is a unique ligand for AMPA receptors. We have characterized pharmacological properties of the ligand using electrophysiology including patch clamp recordings. More recently, a collaborative team with our lab and UCSF group has successfully identified new aspect of AMPA receptors.

Selected publications
  1. Ohki-Hamazaki, H., Watase, K., Yamamoto, K., et al., Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature, 390, 165-169, 1997
  2. Sekiguchi, M., Fleck, M.W., Mayer, M.L., Takeo, J., Chiba, Y., Yamashita, S. and Wada, K., A novel allosteric potentiator of AMPA receptors: 4-[2-(phenylsulfonylamino) ehtylthio]-2,6-difluoro-phenoxyacetamide. J. Neurosci., 17, 5760-5771, 1997
  3. Yamada, K., Wada, E. and Wada, K. Female gastrin-releasing peptide receptor (GRP-R) deficient mice exhibit altered social preference for male conspecifics: implications for GRP/GRP-R modulation of GABAergic function. Brain Res., 894, 281-287, 2001
  4. Sekiguchi,M., Nishikawa, K., Aoki, S. and Wada, K. A desensitization-selective potentiator of AMPA-type glutamate receptors. Br. J. Pharmacol., 136, 1033-1041, 2002
  5. Yamada, K., Santo-Yamada, Y., Wada, E. and Wada, K., Role of bombesin (BN)-like peptides/receptors in emotional behaviour by comparison of three strains of BN-like peptide receptor knockout mice. Mol. Psychiat., 7, 113-117, 2002
  6. Yamada, K., Santo-Yamada, Y. and Wada, K. Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice. Physiol Behav. 78, 303-309, 2003
  7. Maeno, H., Yamada, K., Santo-Yamada, Y., et al. Comparison of the high affinity neurotensin receptor (Ntsr1) and the low affinity neurotensin receptor (Ntsr2) deficient mice reveal a novel function of the Ntsr2 in the thermal nociception. Brain Res, 998, 122-129, 2004
  8. Boyle, R.G., Humphries, J., Mitchell, T., Showell, G.A., Iijima, H., Shimada, H., Arai, T., Ueno, H., Usui, Y., Sakaki, T., Wada, E. and Wada, K. The design of a new potent and selective ligand for the BRS3 receptor, J. Pept. Sci., 11, 136-141, 2005,
  9. Kamichi, S., Wada, E., Aoki, S., Kimura, I. and Wada, K. Immunohistochemical localization of gastrin-releasing peptide receptor in the mouse brain. Brain Res., 1032, 162-170, 2005
  10. Tomita, S., Adesnik, H., Sekiguchi, M., Zhang, W., Wada, K., Howe, J.R., Nicoll, R.A., Bredt, D.S., Stargazin modulates AMPA receptor gating and trafficking by distinct domains, Nature, 435, 1052-1058, 2005
  11. Zushida, K., Sakurai, M., Wada, K. and Sekiguchi, M. Facilitation of extinction learning for contextual fear memory by PEPA: a potentiator of AMPA receptors. J. Neurosci. 27, 158-166, 2007
  12. Hattori, S., Hashimoto, R., Miyakawa, T., Yamanaka, H., Maeno, H., Wada, K. Kunugi, H. Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi. Behav. Brain Res., 80, 69-76, 2007 2007 Feb 28; [Epub ahead of print]
  13. Ohinata, K., Sonoda, S., Inoue, N., Yamauchi, R., Wada, K., Yoshikawa, M. beta-Lactotensin, a neurotensin agonist peptide derived from bovine beta-lactoglobulin, enhances memory consolidation in mice. Peptides. 28, 1470-1474, 2007 2007 Jun 8; [Epub ahead of print]
  14. Oliveira, K.J., Cabanelas, A., Veiga, M.A., Paula, G.S., Ortiga-Carvalho, T.M., Wada, E., Wada, K., Pazos-Moura, C.C. Impaired serum thyrotropin response to hypothyroidism in mice with disruption of neuromedin B receptor. Regul Pept. 146, 213-217, 2008 2007 Sep 14; [Epub ahead of print]
  15. Amano, T., Wada, E., Yamada, D., Zushida, K., Maeno, H., Noda, M., Wada, K., Sekiguchi, M. Heightened amygdala long-term potentiation in neurotensin receptor type-1 knockout mice. Neuropsychopharmacol. 2008 Mar 19; [Epub ahead of print]
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