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Tadahiro Numakawa, PhD
Section Chief of Department of Mental Disorder Research, NCNP (2004-2014). I also contribute as a visiting associate professor of Waseda University, a lecturer of the Tokyo Medical University, and the Tokyo Medical and Dental University. I am a member of the Society for Neuroscience, the American Society for Biochemistry and Molecular Biology, Japan Neuroscience Society, the Japanese Society of Biological Psychiatry, and the Japanese Society for Neurochemistry. I had been given a doctoral degree from the Osaka University in 2000 and given award prizes from Japan Foundation for Aging and Health (2006) and from Japanese Society for Neurochemistry (2009).
 

I am a biologist of cell and molecular biology. I am very interested in function of neurotrophic factors including NGF (Nerve growth factor), BDNF (Brain-derived neurotrophic factor), FGF (Fibroblast Growth Factor) and other factors, because these trophic factors do have multiple function of central nervous system neurons, and are involved in many brain diseases including mental disorders. These days, I have started the studies concerning influence of internal secretion hormone (Estrogen, glucocorticoids, etc.) in (CNS) on neuronal functions. Especially, to clarify the cellular mechanism underlying pathophysiology of mood disorders including depressive disorders , I am trying to investigate the influence of stress hormone on the action of BDNF in CNS . There are many attractive projects of interaction between factors and hormone s at cellular and animal levels. Why don't you join us! As shown in some pictures (Please see them), we are waiting for your joining and let's share fantastic time!

 

Publications
  1. Numakawa T, Richards M, Nakajima S, Adachi N, Furuta M, Odaka H, Kunugi H. The role of brain-derived neurotrophic factor in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition. Front Psychiatry. 2014 Sep 26;5:136. doi: 10.3389/fpsyt.2014.00136. eCollection 2014. Review.
  2. Odaka H, Numakawa T, Adachi N, Ooshima Y, Nakajima S, Katanuma Y, Inoue T, and Kunugi H. Cabergoline, a dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity. PLOS ONE 2014 Jun 10;9(6):e99271. doi: 10.1371/journal.pone.0099271. eCollection 2014.
  3. Numakawa T, Matsumoto T, Ooshima Y, Chiba S, Furuta M, Izumi A, Ninomiya-Baba M, Odaka H, Hashido K, Adachi N, Kunugi H. Impairments in brain-derived neurotrophic factor-induced glutamate release in cultured cortical neurons derived from rats with intrauterine growth retardation: possible involvement of suppression of TrkB/phospholipase C-γ activation. Neurochem Res. 2014 Apr;39(4):785-92. doi: 10.1007/s11064-014-1270-x. Epub 2014 Mar 6.
  4. Katanuma Y, Numakawa T, Adachi N, Yamamoto N, Ooshima Y, Haruki O, Takafumi I, Kunugi H. Phencyclidine rapidly decreases neuronal mRNA of brain-derived neurotrophic factor. Synapse. 2014 Jun;68(6):257-65. doi: 10.1002/syn.21735. Epub 2014 Feb 24.
  5. Suzuki N, Numakawa T, Chou J, de Vega S, Mizuniwa C, Sekimoto K, Adachi N, Kunugi H, Arikawa-Hirasawa E, Yamada Y, Akazawa C. Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling. FASEB J. 2014 Mar;28(3):1386-97. doi: 10.1096/fj.13-241034. Epub 2013 Dec 16.
  6. Jalsrai A, Numakawa T, Ooshima Y, Adachi N, Kunugi H. Phosphatase-mediated intracellular signaling contributes to neuroprotection by flavonoids of Iris tenuifolia Pall. Am J Chin Med. 2014;42(1):119-30. doi: 10.1142/S0192415X14500086.
  7. Numakawa T, Nakajima S, Adachi N, Richards M, Kunugi H. Neurotrophin BDNF and novel molecular targets in depression pathogenesis. Journal of Neurology & Translational Neuroscience 2013 in press.
  8. Numakawa T. The Response of Glucocorticoids to Stress and Functional Alteration of brain-derived neurotrophic Factor. Journal of Neurology & Translational Neuroscience 1: 1004. Published: 20 July 2013.
  9. Furuta M, Numakawa T, Chiba S, Ninomiya M, Kajiyama Y, Adachi N, Akema T, Kunugi H. Estrogen, predominantly via estrogen receptor α, attenuates postpartum-induced anxiety- and depression-like behaviors in female rats. Endocrinology.2013 Oct;154(10):3807-16. doi: 10.1210/en.2012-2136. Epub 2013 Aug 2.
  10. Numakawa T, Adachi N, Richards M, Chiba S, Kunugi H. Brain-derived neurotrophic factor and glucocorticoids: Reciprocal influence in the central nervous system. Neuroscience 2012 Oct 13. pii: S0306-4522(12)01004-4. doi: 10.1016/j.neuroscience.2012.09.073. [Epub ahead of print]
  11. Numakawa T, Adachi N, Richards M, Chiba S, and Kunugi H. The influence of glucocorticoids on neuronal survival and synaptic function. BioMolecular Concepts 2012 Dec; 3(6): 495–504. doi: 10.1515/bmc-2012-0012.
  12. Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, and Kunugi H. Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2012 Oct 1;39(1):112-9. doi: 10.1016/j.pnpbp.2012.05.018. Epub 2012 Jun 1.
  13. Adachi N, Numakawa T, Kumamaru E, Itami C, Chiba S, Iijima Y, Richards M, Katoh-Semba R, Kunugi H. Phencyclidine-Induced Decrease of Synaptic Connectivity via Inhibition of BDNF Secretion in Cultured Cortical Neurons. Cereb Cortex. 2012 Mar 30. [Epub ahead of print]
  14. Numakawa T, Chiba S, Richards MC, Wakabayashi C, Adachi N and Kunugi H. Production of BDNF by stimulation with antidepressant-related substances. Journal of Biological Medicine. 2011; 1(3): 1-10.
  15. Numakawa T, Yamamoto N, Chiba S, Richards M, Ooshima Y, Kishi S, Hashido K, Adachi N, Kunugi H. Growth factors stimulate expression of neuronal and glial miR-132. Neurosci Lett. (2011) Nov 21;505(3):242-7. Epub 2011 Oct 19.
  16. Kumamaru E, Numakawa T, Adachi N, Kunugi H. Glucocorticoid suppresses BDNF-stimulated MAPK/ERK pathway via inhibiting interaction of Shp2 with TrkB. FEBS Lett. (2011) 585(20): 3224-8.
  17. Wakabayashi C, Numakawa T, Ninomiya M, Chiba S, Kunugi H. Behavioral and molecular evidence for psychotropic effects in L:-theanine. Psychopharmacology (Berl). (2012) Feb;219(4):1099-109. Epub 2011 Aug 23.
  18. Numakawa T, Richards M, Adachi N, Kishi S, Kunugi H and Hashido K. MicroRNA function and neurotrophin BDNF. (2011) Neurochemistry International. (2011) Oct;59(5):551-8. Epub 2011 Jun 24.
  19. Numakawa T, Matsumoto T, Numakawa Y, Richards M, Yamawaki S and Kunugi H. Protective action of neurotrophic factors and estrogen against oxidative stress-mediated neurodegeneration. Journal of Toxicology. (2011) 1(5): 133-43.
  20. Numakawa T, Yokomaku D, Richards M, Hori H, Adachi N, and Kunugi H. Functional interactions between steroid hormones and neurotrophin BDNF. World Journal of Biological Chemistry. 2010 May 26;1(5):133-43. doi: 10.4331/wjbc.v1.i5.133.
  21. Kunugi H, Hori H, Adachi N, Numakawa T. Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression. Psychiatry and Clinical Neurosciences. (2010) 64(5): 447-59.
  22. Chiba S, Numakawa T, Ninomiya M, Yoon HS, and Kunugi H. Cabergoline, a dopamine receptor agonist, has an antidepressant-like property and enhances brain-derived neurotrophic factor signaling. Psychopharmacology (Berl) (2010) 211(3): 291-301.
  23. Ninomiya M, Numakawa T , Adachi N, Furuta M, Chiba S, Richards M, Shibata S, and Kunugi H. Cortical neurons from intrauterine growth retardation rats exhibit lower response to neurotrophin BDNF. Neurosci Letters (2010) 476, 104-109.
  24. Kitazawa H, Numakawa T, Adachi N, Kumamaru E, Tuerxun T, Kudo M, Kunugi H: Cyclophosphamide promotes cell survival via activation of intracellular signaling in cultured cortical neurons. Neuroscience Letters (2010) 12, 139-144.
  25. Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, and Kunugi H. BDNF function and intracellular signaling in neurons. Histology and Histopathology (2010) 25: 237-258.
  26. Kawashima H, Numakawa T, Kumamaru E, Adachi N, Mizuno H, Ninomiya M, Kunugi H, Hashido K: Glucocorticoid attenuates brain-derived neurotrophic factor-dependent upregulation of glutamate receptors via the suppression of microRNA-132 expression. Neuroscience (2009) 165, 1301-11.
  27. Tuerxun T, Numakawa T, Adachi N, Kumamaru E, Kitazawa H, Kudo M, Kunugi H: SA4503, a sigma-1 receptor agonist, prevents cultured cortical neurons from oxidative stress-induced cell death via suppression of MAPK pathway activation and glutamate receptor expression. Neuroscience Letters (2009) 469, 303-308.
  28. Numakawa T, Kumamaru E, Adachi N, Yagasaki Y, Izumi A, and Kunugi H. Glucocorticoid receptor interaction with TrkB promotes BDNF-triggered PLC-gamma signaling for glutamate release via a glutamate transporter. Proc. Natl. Acad. Sci. U S A. (2009) 106, 647-652.  →論文の概要はこちら(日本語)
  29. Izumi A, Iijima Y, Noguchi H, Numakawa T, Okada T, Hori H, Kato T, Tatsumi M, Kosuga A, Kamijima K, Asada T, Arima K, Saitoh O, Shiosaka S, and Kunugi H. Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions. Neuropsychopharmacology.(2008) 33, 3237-3245.
  30. Kumamaru E, Numakawa T, Adachi N, Yagasaki Y, Izumi A, Niyaz M, Kudo M, and Kunugi H. Glucocorticoid prevents brain-derived neurotrophic factor-mediated maturation of synaptic function in developing hippocampal neurons through reduction in the activity of mitogen-activated protein kinase. Mol Endocrinol. (2008) 22, 546-558.
  31. Niyaz M, Numakawa T, Matsuki Y, Kumamaru E, Adachi N, Kitazawa H, Kunugi H, and Kudo M. MCI-186 prevents brain tissue from neuronal damage in cerebral infarction through the activation of intracellular signaling. J Neurosci Res. (2007) 85, 2933-2942.
  32. Numakawa Y, Matsumoto T, Yokomaku D, Taguchi T, Niki E, Hatanaka H, Kunugi H, and Numakawa T. 17beta-estradiol protects cortical neurons against oxidative stress-induced cell death through reduction in the activity of mitogen-activated protein kinase and in the accumulation of intracellular calcium. Endocrinology (2007) 148, 627-637.
  33. Hashimoto R, Numakawa T, Ohnishi T, Kumamaru E, Yagasaki Y, Ishimoto T, Mori T, Nemoto K, Adachi N, Izumi A, Chiba S, Noguchi H, Suzuki T, Iwata N, Ozaki N, Taguchi T, Kamiya A, Kosuga A, Tatsumi M, Kamijima K, Weinberger DR, Sawa A, and Kunugi H. Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Hum Mol Genet. (2006) 15, 3024-3033.
  34. Numakawa Y, Numakawa T, Matsumoto T, Yagasaki Y, Kumamaru E, Kunugi H, Taguchi T, Niki E. Vitamin E protected cultured cortical neurons from oxidative stress-induced cell death through the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. J Neurochem. (2006) 97, 1191-1202.
  35. Okada T, Hashimoto R, Numakawa T, Iijima Y, Kosuga A, Tatsumi M, Kamijima K, Kato T, and Kunugi H. A complex polymorphic region in the brain-derived neurotrophic factor (BDNF) gene confers susceptibility to bipolar disorder and affects transcriptional activity. Mol Psychiatry. (2006) 11, 695-703.
  36. Yagasaki Y, Numakawa T, Kumamaru E, Hayashi T, Su TP, and Kunugi H. Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release. J. Biol. Chem. (2006) 281, 12941-12949.
  37. Matsumoto T, Numakawa T, Yokomaku D, Adachi N, Yamagishi S, Numakawa Y, Kunugi H, and Taguchi T. Brain-derived neurotrophic factor-induced potentiation of glutamate and GABA release: different dependency on signaling pathways and neuronal activity. Mol Cell Neurosci. (2006) 31, 70-84.
  38. Yamagishi S, Matsumoto T, Numakawa T, Yokomaku D, Adachi N, Hatanaka H, Yamada M, Shimoke K, and Ikeuchi T. ERK1/2 are involved in low potassium-induced apoptotic signaling downstream of ASK1-p38 MAPK pathway in cultured cerebellar granule neurons. Brain Res. (2005) 1038, 223-230.
  39. Suzuki S, Numakawa T, Shimazu K, Koshimizu H, Hara T, Hatanaka H, Mei L, Lu B, and Kojima M. BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: roles in synaptic modulation. J Cell Biol. (2004) 167, 1205-1215.
  40. Numakawa T, Yagasaki Y, Ishimoto T, Okada T, Suzuki T, Iwata N, Ozaki N, Taguchi T, Tatsumi M, Kamijima K, Straub RE, Weinberger DR, Kunugi H, and Hashimoto R. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet. (2004) 13, 2699-2708.
  41. Numakawa T, Ishimoto T, Suzuki S, Numakawa Y, Adachi N, Matsumoto T, Yokomaku D, Koshimizu H, Fujimori KE, Hashimoto R, Taguchi T, and Kunugi H. Neuronal roles of the integrin-associated protein (IAP/CD47) in developing cortical neurons. J. Biol. Chem. (2004) 279, 43245-43253.
  42. Numakawa T, Nakayama H, Suzuki S, Kubo T, Nara F, Numakawa Y, Yokomaku D, Araki T, Ishimoto T, Ogura A, and Taguchi T. Nerve growth factor-induced glutamate release is via p75 receptor, ceramide, and Ca(2+) from ryanodine receptor in developing cerebellar neurons. J Biol Chem. (2003) 278, 41259-41269.
  43. Nakahata Y, Okumura N, Otani H, Hamada J, Numakawa T, Sano S, and Nagai K. Stimulation of BIT induces a circadian phase shift of locomotor activity in rats. Brain Res. (2003) 976, 194-201.
  44. Yokomaku D, Numakawa T, Numakawa Y, Suzuki S, Matsumoto T, Adachi N, Nishio C, Taguchi T, and Hatanaka H. Estrogen enhances depolarization-induced glutamate release through activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase in cultured hippocampal neurons. Mol Endocrinol. (2003) 17, 831-844.
  45. Nakayama H, Numakawa T, and Ikeuchi T. Nicotine-induced phosphorylation of Akt through epidermal growth factor receptor and Src in PC12h cells. J Neurochem. (2002) 83, 1372-1379.
  46. Numakawa T, Yokomaku D, Kiyosue K, Adachi N, Matsumoto T, Numakawa Y, Taguchi T, Hatanaka H. and Yamada M. Basic fibroblast growth factor evokes a rapid glutamate release through activation of the MAPK pathway in cultured cortical neurons. J Biol Chem. (2002) 277, 28861-28869.
  47. Numakawa T, Yamagishi S, Adachi N, Matsumoto T, Yokomaku D, Yamada M. and Hatanaka H. Brain-derived Neurotrophic Factor-induced potentiation of Ca2+ oscillations in developing cortical neurons. J Biol Chem. (2002) 277, 6520-6529.
  48. Yamada M, Numakawa T, Koshimizu H, Tanabe K, Wada K, Koizumi S, and Hatanaka H. Distinct usages of phospholipase C gamma and Shc in intracellular signaling stimulated by neurotrophins. Brain Res. (2002) 955, 183-190.
  49. Matsumoto T, Numakawa T, Adachi N, Yokomaku D, Yamagishi S, Takei N. and Hatanaka H. Brain-derived neurotrophic factor enhances depolarization-evoked glutamate release in cultured cortical neurons. J Neurochem. (2001) 79, 522-530.
  50. Nakayama H, Numakawa T, Ikeuchi T. and Hatanaka H. Nicotine-induced phosphorylation of extracellular signal-regulated protein kinase and CREB in PC12h cells. J Neurochem. (2001) 79, 489-498.
  51. Numakawa T, Matsumoto T, Adachi N, Yokomaku D, Kojima M, Takei N. and Hatanaka H. Brain-derived neurotrophic factor triggers a rapid glutamate release through increase of intracellular Ca(2+) and Na(+) in cultured cerebellar neurons. J Neurosci Res. (2001) 66, 96-108.
  52. Kojima M, Takei N, Numakawa T, Ishikawa Y, Suzuki S, Matsumoto T, Katoh-Semba R, Nawa H. and Hatanaka H. Biological characterization and optical imaging of brain-derived neurotrophic factor-green fluorescent protein suggest an activity-dependent local release of brain-derived neurotrophic factor in neurites of cultured hippocampal neurons. J. Neurosci Res. (2001) 64, 1-10.
  53. Numakawa T, Takei N, and Hatanaka H. BDNF rapidly induces aspartate release from cultured CNS neurons. Neurosci Res. (2000) 37, 59-65.
  54. Numakawa T, Takei N, Yamagishi S, Sakai N, and Hatanaka H. Neurotrophin-elicited short-term glutamate release from cultured cerebellar granule neurons. Brain Res. (1999) 842, 431-438.
  55. Takei N, Numakawa T, Kozaki S, Sakai N, Endo Y, Takahashi M, and Hatanaka H. Brain-derived neurotrophic factor induces rapid and transient release of glutamate through the non-exocytotic pathway from cortical neurons. J Biol Chem. (1998) 273, 27620-27624.
  56. Satoh T, Numakawa T, Abiru Y, Yamagata T, Ishikawa Y, Enokido Y, and Hatanaka H. Production of reactive oxygen species and release of L-glutamate during superoxide anion-induced cell death of cerebellar granule neurons. J. Neurochem. (1998) 70, 316-324.
  57. Sakai N, Yamada M, Numakawa T, Ogura A, and Hatanaka H. BDNF potentiates spontaneous Ca2+ oscillations in cultured hippocampal neurons. Brain Res. (1997) 778, 318-328.
  58. Shimoke K, Kubo T, Numakawa T, Abiru Y, Enokido Y, Takei N, Ikeuchi T,
    Hatanaka H. Involvement of phosphatidylinositol-3 kinase in prevention of low
    K(+)-induced apoptosis of cerebellar granule neurons
    . Brain Res Dev Brain Res. 1997 Jul 18;101(1-2):197-206.