Molecular dissection of tryptophan metabolism in emotional behavior and its related is diseases.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590362
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Asahikawa Medical College
• Principal Investigator: FUNAKOSHI Hiroshi 旭川医科大学, 医学部, 教授 (40273685)
• Project Period (FY): 2011 – 2013
• Keywords: tryptophan / tryptophan dioxygenase / indoleamine dioxygenase / キヌレニン / 情動 / 代謝 / ノックアウトマウス / TDO

Research Abstract

Tryptophan (Trp) is metabolized via there major pathways; the serotonergic , transaminergic and kynurenergic (Kyn) pathways, and the Kyn pathway contributes about 95% of Trp metabolism. Therefore it has been thought that the elucidation of the roles of Kyn pathway may unvail the roles of Trp metabolisms in a variety of functions, including emotional behaviors. However, because of the presence of two restriction enzymes in Kyn pathway, it has been limited for the analyses of these enzymes in vivo. Here we have generated TDO-KO mice and elucidated the roles of TDO in (1) tryptophan metabolism in the systemic circulation and brain (2) tryptophan metabolismsincluding NAD in different food conditions (3) higher brain function as well as immunological function and (4) emotional disease.

Research Products

• [Journal Article] The kynurenine pathway contributes to long-term neuropsychological changes in experimental pneumococcal meningitis (2014)
  • Author(s): Too LK, McQuillan J, Ball H, Kanai M, Nakamura T, Funakoshi H, McGregor I, Hunt N
  • Journal Title: Behavioural Brain Research Volume: 270C[Epub ahead of print] Pages: 179-195
  • DOI: 10.1016/j.bbr.2014.05.018
• [Journal Article] (2014)
  • Author(s): Bessede A, Gargaro M, Pallotta MT, Matino D, Servillo G, Brunacci C, Bicciato S, Mazza EM, Macchiarulo A, Vacca C, Iannitti R, Tissi L, Volpi C, Belladonna ML,Orabona C, Bianchi R, Lanz TV, Platten M, Della Fazia MA, Piobbico D, Zelante T, Funakoshi H, et al
  • Journal Title: Nature
  • DOI: 10.1038/nature13323
• [Journal Article] Contributions of Tryptophan 2,3-dioxygenase and Indoleamine 2,3-dioxygenase to the Conversion of D-Tryptophan to Nicotinamide Analyzed by using Tryptophan 2,3-dioxygenase -Knockout Mice (2014)
  • Author(s): Maeta A, Sano M, Fukuwatari T, Funakoshi H, Nakamura T, Shibata K
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Pages: 1-4
  • DOI: 10.1080/09168451.2014.905185
• [Journal Article] The niacin required for optimum growth can be synthesized from L-tryptophan in growing mice lacking tryptophan-2,3-dioxygenase (2013)
  • Author(s): Terakata M, Fukuwatari T, Kadota E, Sano M, Kanai M, Nakamura T, Funakoshi H, Shibata K
  • Journal Title: J Nutr Volume: 143(7) Pages: 1046-1051
  • DOI: 10.3945/jn.113.176875
• [Journal Article] Tryptophan-restriction diets help to maintain L-tryptophan homeostasis in tryptophan 2,3-dioxygenase knockout mice (2013)
  • Author(s): Maeta A, Fukuwatari T, Funakoshi H, Nakamura T, Shibata K
  • Journal Title: Int J Tryptophan Res. Volume: 6(Suppl 1) Pages: 55-65
  • DOI: 10.4137/IJTR.S12206
• [Journal Article] Overexpression of HGF attenuates the degeneration of Purkinje cells and Bergmann glia in a knockin mouse model of spinocerebellar ataxia type 7 (2012)
  • Author(s): Noma S, Ohya-Shimada W, Kanai M, Ueda K, Nakamura T, Funakoshi H
  • Journal Title: Neurosci Res.(Corresponding author) Volume: 773(2) Pages: 115-121
• [Journal Article] Hepatocyte growth factor (HGF) overexpression in the nervous system enhances learning and memory performance in mice (2012)
  • Author(s): Kato T, Funakoshi H, Kadoyama K, Noma S, Kanai M, Ohya-Shimada W, Mizuno S, Doe N, Taniguchi T, Nakamura T
  • Journal Title: J. Neurosci. Res. (Corresponding authors) Volume: 90(9) Pages: 1743-1755
• [Journal Article] Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury (2011)
  • Author(s): Kitamura K, Fujiyoshi K, Yamane J, Toyota F, Hikishima K, Nomura T, Funakoshi H, Nakamura T, Aoki M, Toyama Y, Okano H, Nakamura M
  • Journal Title: PLoS One Volume: 6(11) Pages: e27706
  • DOI: 10.1371/journal.pone.0027706
• [Journal Article] Strong neurogenesis, angiogenesis and anti-fibrosis of hepatocyte growth factor in rats brain after transient middle cerebral artery occlusion (tMCAO) (2011)
  • Author(s): Shang J, Deguchi K, Ohta Y, Liu N, Zhang X, Tian F, Yamashita T, Ikeda Y, Matsuura T, Funakoshi H, Nakamura T, Abe K
  • Journal Title: J Neurosci Res Volume: 89(1) Pages: 86-95
• [Remarks]
  • URL: http://www.asahikawa-med.ac.jp/arec/funakoshis_labo/
• [Remarks]
  • URL: http://www.asahikawa-med.ac.jp/arec/