|Japanese | English|
|Organization:||Fujita Health University School of Medicine|
|NAMEF||Department of Physiology|
|Professor||Akira Ota, M.D., Ph.D.|
|Associate Professor||Akira Nakashima, Ph.D.|
|Associate Professor||Hiroshi Nagasaki, M.D., Ph.D.|
|Senior Assistant Professor||Yoko S Kaneko, Ph.D.|
|Assistant Professor||Yu Kodani, Ph.D.|
|Akira Ota, M.D., Ph.D., started his career as an internist (endocrinologist and diabetologist) at Nagoya the 2nd Red Cross Hospital in 1978 and had worked as a clinician for about 10 years at a couple of hospitals. His encounter with a 17-year-old girl suffering from insulin-resistant DM (the first case of insulin receptor anomaly reported in Japan) determined his field of research. Coming back home from the studying abroad at the Diabetes Branch of National Institute of Health U.S.A. in 1989, he had gradually shifted his research target from endocrinology to neuroscience. The main theme currently undertaken in the department belongs to the field of gNeuroendocrinologyh in a broad sense. The concrete research targets in this laboratory are summarized into the following 4 projects.
(1) the pathophysiological regulation of tyrosine hydroxylase activity, a rate-limiting enzyme in catecholamine synthesizing pathway
(2) the investigation on the roles of microglia involved in the lipopolysaccharide-provoked neurodegeneration in CNS
(3) the investigation on the increase in the appetite induced by atypical antipsychotics
(4) the building-up of the regenerative therapy for central diabetes insipidus by using murine ES cells
According to the skills available in molecular biology and protein chemistry, as a whole, these 4 projects have been in a progress slowly, but readily and steadily. They have dealt with the overall processes from the gene to protein expressions under the viewpoint of the interactions between nervous and hormonal systems. Akira Nakshima, Ph.D., is assigned to investigate the project (1); Yoko S Kaneko, Ph.D., to the project (2); all members to the project (3); and Hiroshi Nagasaki, M.D., Ph.D., and Yu Kodani, Ph.D., to the project (4). All members of the department devote themselves to their research every day. The fruitful results obtained in our work have been in public as the original articles and we pride ourselves on our achievements.
|All articles except for the two papers (Mazzulli et al. 2006; Nomura et al. 1998) were corresponded by the member of the department.
Nakashima A, Ota A, Kaneko YS, Mori K, Nagasaki H, Nagatsu T (2013) A possible pathophysiological role of tyrosine hydroxylase in Parkinsonfs disease suggested by postmortem brain biochemistry: a contribution for the special 70th birthday symposium in honor of Prof. Peter Riederer. J Neural Transm. 120(1):49-54.
Nakashima A (2012) Proteasomal degradation of tyrosine hydroxylase and neurodegeneration. J Neurochem. 120(2):199-201.
Kaneko YS, Ota A, Nakashima A, Mori K, Nagatsu I, Nagatsu T (2012) Regulation of oxidative stress in long-lived lipopolysaccharide-activated microglia. Clin Exp Pharmacol Physiol. 39(7):599-607.
Kaneko YS, Nakashima A, Mori K, Nagatsu T, Nagatsu I, Ota A (2012) Microglial activation in neuroinflammation: implications for the etiology of neurodegeneration. Neurodegener Dis. 10(1-4):100-103.
Nagasaki H, Kondo T, Fuchigami M, Hashimoto H, Sugimura Y, Ozaki N, Arima H, Ota A, Oiso Y, Hamada Y (2012) Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNF¿ enhances GPR84 expression in adipocytes. FEBS Lett. 586(4):368-372.
Ota A, Nakashima A, Kaneko YS, Mori K, Nagasaki H, Takayanagi T, Itoh M, Kondo K, Nagatsu T, Ota M (2012) Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells. J Neural Transm. 119(11):1327-1342.
Mori K, Kaneko YS, Nakashima A, Nagasaki H, Nagatsu T, Nagatsu I, Ota A (2012) Subventricular zone under the neuroinflammatory stress and Parkinsonfs disease. Cell Mol Neurobiol. 32(5):777-785.
Nakashima A, Mori K, Kaneko YS, Hayashi N, Nagatsu T, Ota A (2011) Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme. Biochem Biophys Res Commun. 407(2):343-347.
Takami G, Ota M, Nakashima A, Kaneko YS, Mori K, Nagatsu T, Ota A (2010) Effects of atypical antipsychotics and haloperidol on PC12 cells: only aripiprazole phosphorylates AMP-activated protein kinase. J Neural Transm. 117(10):1139-1153.
Mori K, Kaneko YS, Nakashima A, Nagatsu T, Nagatsu I, Ota A (2010) Peripherally injected lipopolysaccharide induces apoptosis in the subventricular zone of young adult mice. Neurosci Lett. 481(2):126-130.
Kaneko YS, Nakashima A, Mori K, Nagatsu T, Nagatsu I, Ota A (2009) Lipopolysaccharide extends the lifespan of mouse primary-cultured microglia. Brain Res. 1279:9-20.
Nakashima A, Hayashi N, Kaneko YS, Mori K, Sabban EL, Nagatsu T, Ota A (2009) Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines. J Neural Transm. 116(11):1355-1362.
Ota A, Mori K, Kaneko YS, Nakashima A, Nagatsu I, Nagatsu T (2008) Peripheral lipopolysaccharide administration affects the olfactory dopamine system in mice. Ann N Y Acad Sci. 1148:127-135.
Nakashima A, Hayashi N, Kaneko YS, Mori K, Sabban EL, Nagatsu T, Ota A (2007) RNAi of 14-3-3Å protein increases intracellular stability of tyrosine hydroxylase. Biochem Biophys Res Commun. 363(3):817-821.
Ota A, Kaneko YS, Mori K, Nakashima A, Nagatsu I, Nagatsu T (2007) Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice. Stress 10(2):131-136.
Ota M, Nakashima A, Kaneko YS, Mori K, Takami G, Ota A (2007) Risperidone reduces mRNA expression levels of Sulfonylurea Receptor 1 and TASK1 in PC12 cells. Neurosci Lett. 412(3):254-258.
Mazzulli JR, Mishizen AJ, Giasson BI, Lynch DR, Thomas SA, Nakashima A, Nagatsu T, Ota A, Ischiropoulos H (2006) Cytosolic catechols inhibit ¿-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediates. J Neurosci. 26(39):10068-10078.
Kaneko YS, Mori K, Nakashima A, Sawada M, Nagatsu I, Ota A (2005) Peripheral injection of lipopolysaccharide enhances expression of inflammatory cytokines in murine locus coeruleus: possible role of increased norepinephrine turnover. J Neurochem. 94(2):393-404.
Kaneko YS, Mori K, Nakashima A, Nagatsu I, Nagatsu T, Ota A (2005) Corticotropin-releasing factor receptor antagonist attenuates LPS-induced increase of GTP cyclohydrolase I expression at murine locus coeruleus. Biogenic Amines 19;289-297.
Nakashima A, Hayashi N, Kaneko YS, Mori K, Egusa H, Nagatsu T, Ota A (2005) Deletion of N-terminus of human tyrosine hydroxylase type 1 enhances stability of the enzyme in AtT-20 cells. J Neurosci Res. 81(1):110-120.
Nakashima A, Kaneko YS, Mori K, Nagatsu T, Ota A (2005) The phosphorylation of Ser40 of tyrosine hydroxylase has no effect on the stability of the enzyme in PC12 cells. Biogenic Amines 19:279-288.
Mori K, Kaneko YS, Nakashima A, Nagatsu I, Takahashi H, Ota A (2005) Peripheral lipopolysaccharide induces apoptosis in the murine olfactory bulb. Brain Res. 1039(1-2):116-129.
Ota M, Mori K, Nakashima A, Kaneko YS, Takahashi H, Ota A (2005) Resistance to excessive bodyweight gain in risperidone-injected rats. Clin Exp Pharmacol Physiol. 32(4):279-287.
Ota M, Mori K, Nakashima A, Kaneko YS, Takami G, Ota A (2005) mRNA Expression levels of leptin-related substances can be modified in risperidone-injected rats. Biogenic Amines 19(4-6):299-308.
Fujiwara K, Mori K, Kaneko YS, Nakashima A, Nagasaka A, Itoh M, Ota A (2004) Tetrahydrobiopterin biosynthesis in white and brown adipose tissues is enhanced following intraperitoneal administration of bacterial lipopolysaccharide. Biochim Biophys Acta 1670(3):181-198.
Nakashima A, Ota A, Sabban EL (2003) Interactions between Egr1 and AP1 factors in regulation of tyrosine hydroxylase transcription. Brain Res Mol Brain Res. 112(1-2):61-69.
Mori K, Kaneko YS, Nakashima A, Fujiwara K, Nagatsu I, Ota A (2003) Effect of peripheral lipopolysaccharide injection on dopamine content in murine anterior olfactory nucleus. J Neural Transm. 110(1):31-50.
Kaneko YS, Mori K, Nakashima A, Nagatsu I, Ota A (2003) Peripheral administration of lipopolysaccharide enhances the expression of guanosine triphosphate cyclohydrolase I mRNA in murine locus coeruleus. Neuroscience 116(1):7-12.
Ota M, Mori K, Nakashima A, Kaneko YS, Fujiwara K, Itoh M, Nagasaka A, Ota A (2002) Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats. Clin Exp Pharmacol Physiol. 29(11):980-989.
Nakashima A, Kaneko YS, Mori K, Fujiwara K, Tsugu T, Suzuki T, Nagatsu T, Ota A (2002) The mutation of two amino acid residues in the N-terminus of tyrosine hydroxylase (TH) dramatically enhances the catalytic activity in neuroendocrine AtT-20 cells. J Neurochem. 82(1):202-206.
Kaneko YS, Mori K, Nakashima A, Nagatsu I, Nagatsu T, Ota A (2001) Determination of tetrahydrobiopterin in murine locus coeruleus by HPLC with fluorescence detection. Brain Res Brain Res Protoc. 8(1):25-31.
Ota M, Nakashima A, Ikemoto K, Nojima S, Tanaka M, Okuda M, Koga H, Mori K, Kaneko YS, Fujiwara K, Yamamoto H, Nagatsu T, Ota A (2001) Exon 3 of tyrosine hydroxylase gene: lack of association with Japanese schizophrenic patients. Mol Psychiatry 6(3):315-319.
Kaneko YS, Ikemoto K, Mori K, Nakashima A, Nagatsu I, Ota A (2001) Expression of GTP cyclohydrolase I in murine locus ceruleus is enhanced by peripheral administration of lipopolysaccharide. Brain Res. 890(2):203-210.
Nakashima A, Hayashi N, Mori K, Kaneko YS, Nagatsu T, Ota A (2000) Positive charge intrinsic to Arg37-Arg38 is critical for dopamine inhibition of the catalytic activity of human tyrosine hydroxylase type 1. FEBS Lett. 465(1):59-63.
Nakashima A, Mori K, Nagatsu T, Ota A (1999) Expression of human tyrosine hydroxylase type I in Escherichia coli as a protease-cleavable fusion protein. Short communication. J Neural Transm. 106(9-10):819-824.
Nakashima A, Mori K, Suzuki T, Kurita H, Otani M, Nagatsu T, Ota A (1999) Dopamine inhibition of human tyrosine hydroxylase type 1 is controlled by the specific portion in the N-terminus of the enzyme. J Neurochem. 72(5):2145-2153.
Nomura T, Tazawa M, Ohtsuki M, Sumi-Ichinose C, Hagino Y, Ota A, Nakashima A, Mori K, Sugimoto T, Ueno O, Nozawa Y, Ichinose H, Nagatsu T (1998) Enzymes related to catecholamine biosynthesis in Tetrahymena pyriformis. Presence of GTP cyclohydrolase I. Comp Biochem Physiol B Biochem Mol Biol. 120(4):753-760.
Mori K, Nakashima A, Nagatsu T, Ota A (1997) Effect of lipopolysaccharide on the gene expression of the enzymes involved in tetrahydrobiopterin de novo biosynthesis in murine neuroblastoma cell line N1E-115. Neurosci Lett. 238(1-2):21-24.
Ota A, Nakashima A, Mori K, Nagatsu T (1997) Effects of dopamine on N-terminus-deleted human tyrosine hydroxylase type 1 expressed in Escherichia coli. Neurosci Lett. 229(1):57-60.
Thu May 16 09:07:13 JST 2013