Pharmaceutical Sciences

1981 B.S.

Meijo University, Nagoya, Japan

1983 M.S.

Pharmacology, Meijo University, Nagoya, Japan

1991 Ph.D.

Pharmacology, Meijo University, Nagoya, Japan
Position Held:

1983-1993

Research Scientist, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan

1987-1989

Visiting Scientist, Department of Neuroscience, The Johns Hopkins University School of Medicine (Prof. Joseph T. Coyle)

1993-1998

Clinical Pharmacist, Department of Hospital Pharmacy, Nagoya University School of Medicine

1998-2002

Associate Professor and Vice Director, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine

2002-2004

Professor and Chairman, Laboratory of Neuropsychopharmacology, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kanazawa University

2004-2007.07

Professor and Chairman, Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University

2007.08-present

Professor and Director, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine

Neuropharmacological study on the development of novel drugs in neuropsychiatric disorders

We have been studying the molecular and cellular mechanism of learning and memory as well as emotional behaviors in rodents. So far, we demonstrated the involvement of nitric oxide and BDNF in the hippocampus-dependent spatial working memory processes. Furthermore, we have clarified the role of oxidative stress, inducible nitric oxide synthase (iNOS) and a subsequent protein nitration in the brain dysfunction of an animal model of Alzheimer’s disease in which the animals were continuously infused with amyloid b protein into the lateral ventricle. We have also investigated the molecular and cellular mechanism underlying the development and relapse of drug addiction in animal models. We identified the tissue plasminogen activator-plasmin system, matrix metalloproteinase-2 (MMP-2) and MMP-9 as endogenous pro-addictive factors, while TNF-α and GDNF are considered anti-addictive factors.

In the research supported by the G-COE program, we focus on the neuropharmacological study to develop novel drugs in neuropsychiatric disorders such as Alzheimer’s disease and schizophrenia. In the study of schizophrenia, we attempt to develop the novel animal model in which mice with mutant DISC1 or other susceptibility genes are subjected to psychosocial stress.

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1. Arai S et al. Involvement of pallidotegmental neurons in methamphetamine- and MK-801-induced impairment of prepulse inhibition of the acoustic startle reflex in mice: reversal by GABAB receptor agonist baclofen. Neuropsychopharmacology in press (2008)
2. Alkam T et al. The extensive nitration of neurofilament light chain in the hippocampus is associated with the cognitive impairment induced by amyloid beta in mice. J. Pharmacol. Exp. Ther. in press (2008)
3. Ibi D et al. Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice. J. Neurochem. 105: 436-444 (2008)
4. Yijin Y et al. Enduring vulnerability to reinstatement of methamphetamine-seeking behavior in glial cell line-derived neurotrophic factor mutant mice. FASEB J. 21: 1994-2004 (2007)
5. Jin D et al. CD38 is critical for social behavior by regulating oxytocin secretion. Nature 446: 41-45 (2007)
6. Takahashi K et al. Neural circuits containing pallidotegmental GABAergic neurons are involved in the prepulse inhibition of the startle reflex in mice. Biol. Psychiatry 62: 148-157 (2007)
7. Nagai T et al. The rewards of nicotine: regulation by tissue plasminogen activator-plasmin system through protease activated receptor-1. J. Neurosci. 26: 12374-12383 (2006)
8. Kamei H et al. Repeated methamphetamine treatment impairs recognition memory through a failure of novelty-induced ERK 1/2 activation in the prefrontal cortex. Biol. Psychiatry 59: 75-84 (2006)
9. Matsuoka Y et al. Prostaglandin E receptor EP1 controls impulsive behavior under stress. Proc. Natl. Acad. Sci. USA 102: 16066-16071 (2005)
10. Nagai T et al. Tissue plasminogen activator-plasmin system participates in the rewarding effect of morphine by regulating dopamine release. Proc. Natl. Acad. Sci. USA 101: 3650-3655 (2004)
11. Nakajima A et al. Role of TNF-a in methamphetamine-induced drug dependence and neurotocicity. J. Neurosci. 24: 2212-2225 (2004)
12. Mamiya T et al. Neuronal mechanism of nociceptin-induced modulation of learning and memory: Involvement of N-methyl-D-aspartate receptors. Mol. Psychiatry 8: 752-765 (2003)
13. Nagai T et al. Cognition impairment in the genetic model of aging, klotho gene mutant mice: a role of oxidative stress. FASEB J. 17: 50-52 (2003)
14. Mizuno M et al. Phosphatidylinositol 3-kinase: a molecule mediating BDNF-dependent spatial memory formation. Mol. Psychiatry 8: 217-224 (2003)
15. Tran MH et al. Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction. Mol. Psychiatry 8: 407-412 (2003)
16. Miyamoto Y et al. Lower sensitivity to stress and altered monoaminergic neuronal function in mice lacking the NMDA receptor e4 subunit. J. Neurosci. 22: 2335-2342 (2002)
17. Tran MH et al. Amyloid β-peptide induces nitric oxide production in rat hippocampus: association with cholinergic dysfunction and amelioration by inducible nitric oxide synthase inhibitors. FASEB J. 15: 1407-1409 (2001)
18. Miyamato Y et al. Hyperfunction of dopaminergic and serotonergic neuronal systems in mice lacking NMDA receptor e1 subunit. J. Neurosci. 21: 750-757 (2001)
19. Mizuno M et al. Involvement of BDNF in spatial memory formation and maintenance in a radial arm maze test in rats. J. Neurosci. 20: 7116-7121

Research Award from the Japanese Pharmacological Society (1997)
The Pharmaceutical Society of Japan Award for Divisional Scientific Promotions (2008)