我々の研究室では、本能行動や学習行動が脳でどのように制御されているのかを明らかにする研究を行っています。キーワードは学習・記憶、性行動、睡眠、概日リズム、環境要因、ストレス、トラウマ、です。

哺乳類では、過度なストレスによるトラウマ記憶によりオスの性的モチベーションが長期間低下することが知られています。しかし、そのメカニズムは謎に包まれています。
　最近我々は、昆虫であるショウジョウバエでも同様に過剰ストレスによりオスの求愛活性が低下することを見出しました。ショウジョウバエ遺伝学を利用して、ストレスにより求愛活性が低下するメカニズムを明らかにする研究を進めています。

　ビデオトラッキング解析、そして、光遺伝学と脳イメージングを駆使してストレスにより活性化するニューロンの同定と、ストレスが求愛を抑制する仕組みを回路レベルで解明することに取り組んでいます。、

哺乳類では、過度なストレスによるトラウマ記憶によりオスの性的モチベーションが長期間低下することが知られています。昆虫であるショウジョウバエでも同様の現象が知られており、「求愛条件付け」と呼ばれています。オスはメスの性フェロモンに反応して求愛を始めますが、一度交尾したメスは、求愛するオスに対して過度なストレス（性交拒絶、オスが忌避する匂い物質）を与えます。このメスからのストレス刺激に長時間さらされたオスは、その後、未交尾のメスとつがわせてもあまり求愛しなくなります。求愛条件付けでは、メスからストレスを受けたオスのトラウマ記憶により、求愛モチベーションが低下すると考えられています。このようなハエのトラウマ記憶を利用して、

　動物は自身の経験を通して記憶を獲得し、それを維持して生存に役立てています。これまでに多くのモデル動物で記憶獲得の分子機構が明らかにされてきましたが、獲得した記憶を長期間維持する機構はよく分かっていませんでした。我々は、ショウジョウバエ（以下、ハエ）が環境光を利用して長期記憶を維持していることを発見し、この「光による記憶維持」の分子メカニズムを明らかにする研究を行いました。その結果、光により神経ペプチドPDF（神経伝達物質の一種）が放出されると、ハエ記憶中枢におけるCREBという転写因子が活性化し、記憶中枢で新規遺伝子が発現することで長期記憶が維持されることを突き止めました。この成果は、光の有無や遺伝学的な操作により、長期記憶の維持もしくは消失をコントロールできる可能性を示しています。現在はCREBのターゲットを明らかにする研究を進めています。

　長期記憶は一度獲得されると簡単には忘却されず、消去が困難です。そのため、トラウマによる記憶など、動物にとってネガティブな記憶が残り続けてしまうという弊害をもたらしてしまいます。我々の研究成果は、将来、トラウマ記憶の消去技術の発展に寄与するかもしれません。

関連情報

最近の研究業績

1. Watanabe, K. and *Sakai, T. (2015) Knockout mutations of insulin-like peptides enhance sexual receptivity in Drosophila virgin females. Genes and Genetic System (in press)
2. Ohashi, H. and *Sakai, T. (2015) Novel behavioral assay of wasabi avoidance in Drosophila using a video tracking system. Appl. Entmol. Zool. 50: 137-142.
3. Sato, S., Kitamoto, T. and *Sakai, T. (2014) Modulation of innate and learned sexual behaviors by the TRP channel Painless expressed in the fruit fly brain: behavioral genetic analysis and its implications. Front. Behav. Neurosci. 8: Article 400 (doi: 10.3389/fnbeh.2014.00400)
4. *Sakai, T., Watanabe, K., Ohashi, H., Sato, S., Inami, S., Shimada, N., Kitamoto, T. (2014) Insulin-producing cells regulate the sexual receptivity through the Painless TRP channel in Drosophila virgin females. PLoS ONE 9(2): e88175
5. Amano A, Tsunoda M, Aigaki T, Maruyama N, Ishigami A. (2013) Effect of ascorbic acid deficiency on catecholamine synthesis in adrenal glands of SMP30/GNL knockout mice. Eur J Nutr. In Press.
6. Trindade LS, Aigaki T, Peixoto AA, Balduino A, Mânica da Cruz IB, Heddle JG. (2013) A novel classification system for evolutionary aging theories. Front Genet. 4:25.
7. Cheng Z, Tsuda M, Kishita Y, Sato Y, Aigaki T. (2013) Impaired energy metabolism in a Drosophila model of mitochondrial aconitase deficiency. Biochem Biophys Res Commun. 433, 145-150.
8. Aizawa S, Senda M, Harada A, Maruyama N, Ishida T, Aigaki T, Ishigami A, Senda T. (2013) Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase. PLoS One. 8, e53706.
9. Kadengodlu PA, Aigaki T, Abe H, Ito Y. (2013) Cationic cholesterol-modified gelatin as an in vitro siRNA delivery vehicle. Mol Biosyst. 9, 965-968.
10. Sakai, T., Sato, S., Ishimoto, H., *Kitamoto, T. (2013) Significance of the centrally expressed TRP channel Painless in Drosophila courtship memory. Learning & Memory 20: 34-40.
11. Asano T., Taoka M., Shinkawa T., Yamauchi Y., Isobe T., Sato D.（2013）Identification of a cuticle protein with unique repeated motifs in the silkworm, Bombyx mori. Insect Biochem. Molec. Biol. 43, 344-351.
12. 八木勇三，佐藤由紀子，村松由記子，原高明，相垣敏郎 (2013) ショウジョウバエの寿命に対する赤ワイン由来ポリフェノールProtocatechuic acid の効果. Food function (in press).
13. *Sakai, T., Inami, S., Sato, S., Kitamoto, T. (2012) Fan-shaped body neurons are involved in period-dependent regulation of long-term courtship memory in Drosophila. Learning & Memory 19: 571-574.
14. Tomioka S, Aigaki T, Matsuo T. (2012) Conserved cis-regulatory elements of two odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. Genes Genet Syst. 87, 323-329.
15. Kadengodlu PA, Hebishima T, Takeshima SN, Ito M, Liu M, Abe H, Aida Y, Aigaki T, Ito Y. (2012) Positively charged cholesterol-recombinant human gelatins foster the cellular uptake of proteins and murine immune reactions. J Nanomedicine 7, 5437-5450.
16. Amano A, Tsunoda M, Aigaki T, Maruyama N, Ishigami A. (2012) Age-related changes of dopamine, noradrenaline and adrenaline in adrenal glands of mice. Geriatr Gerontol. 13, 490-496.
17. Nakagawa-Yagi Y, Sato Y, Matsumoto E, Nakatsuka SI, Sakaki T, Muramatsu Y, Hara T, Aigaki T. (2012) Pharmacological modulation of histone demethylase activity by a small molecule isolated from subcritical water extracts of Sasa senanensis leaves prolongs the lifespan of Drosophila melanogaster. BMC Complement Altern Med. 12,101.
18. Trindade LS, Balduino A, Aigaki T, Heddle JG. (2012) Senemorphism: a novel perspective on aging patterns and its implication for diet-related biology. Biogerontology. 13,457-466.
19. Takeo S, Swanson SK, Nandanan K, Nakai Y, Aigaki T, Washburn MP, Florens L, Hawley RS. (2012) Shaggy/glycogen synthase kinase 3β and phosphorylation of Sarah/regulator of calcineurin are essential for completion of Drosophila female meiosis. Proc Natl Acad Sci U S A. 109, 6382-6389.
20. Kishita Y, Tsuda M, Aigaki T. (2012) Impaired fatty acid oxidation in a Drosophila model of mitochondrial trifunctional protein (MTP) deficiency. Biochem Biophys Res Commun. 419, 344-349.
21. Harada E, Nakagawa J, Asano T, Taoka M, Sorimachi H, Ito Y, Aigaki T, Matsuo T. (2012) Functional evolution of duplicated odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. PLoS One. 7, e29710.
22. Takeo S, Swanson SK, Nandanan K, Nakai Y, Aigaki T, Washburn MP, Florens L, Hawley RS. (2012) Shaggy/glycogen synthase kinase 3β and phosphorylation of Sarah/regulator of calcineurin are essential for completion of Drosophila female meiosis. Proc Natl Acad Sci U S A, 109, 6382-6389.
23. Kishita Y, Tsuda M, Aigaki T. (2012) Impaired fatty acid oxidation in a Drosophila model of mitochondrial trifunctional protein (MTP) deficiency. Biochem Biophys Res Commun. 419, 344-349.
24. Harada E, Nakagawa J, Asano T, Taoka M, Sorimachi H, Ito Y, Aigaki T, Matsuo T. (2012) Functional evolution of duplicated odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. PLoS One, 7, e29710.
25. Kourosh Shahpasand, Isao Uemura, Taro Saito, Tsunaki Asano, Kenji Hata, Keitaro Shibata, Yoko Toyoshima, Masato Hasegawa and Shin-ichi Hisanaga,（2012）Regulation of mitochondrial transport and inter-microtubule spacing by Tau phosphorylation at the sites hyperphosphorylated in Alzheimer’s disease, J. Neuroscience, 32, 2430-2441.
26. Tomita J, Mitsuyoshi M, Ueno T, Aso Y, Tanimoto H, Nakai Y, Aigaki T, Kume S, Kume K. (2011) Pan-neuronal knockdown of calcineurin reduces sleep in the fruit fly, Drosophila melanogaster. J Neurosci. 31, 13137-13146.
27. Amano A, Handa S, Aigaki T, Shigemoto K, Maruyama N, Ishigami A. (2011) Establishment and characterization of hepatocytes from an Immortomouse/SMP30/GNL knockout mouse hybrid lacking vitamin C to study vitamin C transport. J Biochem. 150, 671-678.
28. Nakai Y, Horiuchi J, Tsuda M, Takeo S, Akahori S, Matsuo T, Kume K, Aigaki T. (2011) Calcineurin and its regulator sra/DSCR1 are essential for sleep in Drosophila. J Neurosci, 3012759-12766.
29. Wang W, Hara S, Liu M, Aigaki T, Shimizu S, Ito Y. (2011) Polypeptide aptamer selection using a stabilized ribosome display. J Biosci Bioeng, 112, 515-517.
30. Rotkopf S, Hamberg Y, Aigaki T, Snapper SB, Shilo BZ, Schejter ED. (2011) The WASp-based actin polymerization machinery is required in somatic support cells for spermatid maturation and release. Development, 188, 105-125.
31. 坂井貴臣（2011）「ショウジョウバエメスの性行動の神経遺伝学的研究」　比較生理生化学 28: 225-230.
32. Brumby AM, Goulding KR, Schlosser T, Loi S, Galea R, Khoo P, Bolden JE, Aigaki T, Humbert PO, Richardson HE. (2011） Identification of Novel Ras-cooperating Oncogenes in Drosophila melanogaster: A RhoGEF/Rho-family/JNK Pathway is a Central Driver of Tumorigenesis. Genetics, 188, 105-125.
33. Funakoshi M, Tsuda M, Muramatsu K, Hatsuda H, Morishita S, Aigaki T. (2011） A gain-of-function screen identifies wdb and lkb1 as lifespan-extending genes in Drosophila. Biochem Biophys Res Commun. 405, 667-72.
34. Sakai T and Aigaki T. (2010) The Drosophila calcineurin regulator, Sarah, is involved in male courtship. NeuroReport 21: 985-988.
35. Sakai T and Aigaki T. (2010) Overexpression of a repressor isoform of CrebB-17A lengthens courtship break in the fruit fly Drosophila melanogaster (Diptera: Drosophilidae). Applied Entomology and Zoology 45: 533-539.
36. Tsuda M, Kawaida R, Kobayashi K, Shinagawa A, Sawada T, Yamada R, Yamamoto K, Aigaki T. (2010） POSH promotes cell survival in Drosophila and in human RASF cells. FEBS Lett, 584, 4689-4694.
37. Ueyama M, Akimoto Y, Ichimiya T, Ueda R, Kawakami H, Aigaki T, Nishihara S. (2010） Increased apoptosis of myoblasts in Drosophila model for the Walker-Warburg syndrome. PLoS One, 5, e11557.
38. Yasukawa J, Tomioka S, Aigaki T, Matsuo T. (2010） Evolution of expression patterns of two odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. Gene, 467, 25-34.
39. Yamazaki D, Horiuchi J, Miyashita T, Saitoe M. (2010） Acute inhibition of PKA activity at old ages ameliorates age-related memory impairment in Drosophila. J Neurosci, 30, 15573-15577.
40. Tsuda M, Ootaka R, Ohkura C, Kishita Y, Seong KH, Matsuo T, Aigaki T. (2010） Loss of Trx-2 enhances oxidative stress-dependent phenotypes in Drosophila. FEBS Lett, 584, 3398-401.
41. Takeo S, Hawley RS, Aigaki T. (2010） Calcineurin and its regulation by Sra/RCAN is required for completion of meiosis in Drosophila. Dev Biol, 344, 957-67.
42. Tsuda M, Kobayashi T, Matsuo T, Aigaki T. (2010） Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila. FEBS Lett, 584, 2916-20.
43. Amano A, Aigaki T, Maruyama N, Ishigami A. (2010) Ascorbic acid depletion enhances expression of the sodium-dependent vitamin C transporters, SVCT1 and SVCT2, and uptake of ascorbic acid in livers of SMP30/GNL knockout mice. Arch Biochem Biophys. 496, 38–44.
44. Ahsan, B., Saito, TL., Hashimoto, S., Muramatsu, K., Tsuda, M., Sasaki, A., Matsushima, K., Aigaki, T. and Morishita, S. (2009) MachiBase: a Drosophila melanogaster 5'-end mRNA transcription database. Nucleic Acids Res. 37, D49-53.
45. Tsubouchi, A., Tsuyama, T., Fujioka, M., Kohda, H., Okamoto-Furuta, K., Aigaki, T. and Uemura, T. (2009) Mitochondrial Protein Preli-like Is Required for Development of Dendritic Arbors and Prevents Their Regression in the Drosophila Sensory Nervous System. Development, 136, 3757-3766.
46. Sakai T, Kasuya J, Kitamoto T and Aigaki T. (2009) The Drosophila TRPA channel, Painless, regulates sexual receptivity in virgin females. Genes, Brain and Behavior 8: 546-557.
47. Ishimoto H,Sakai T, and Kitamoto T. (2009) Ecdysone signaling regulates courtship long-term memory formation in adult Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 106: 6381-6386.
48. Matsuo, T. (2008) Rapid evolution of two odorant-binding protein genes, Obp57d and Obp57e, in the Drosophila melanogaster species group. Genetics 178:1061-1072.
49. Harada, E., Haba, D., Aigaki, T., Matsuo, T. (2008) Behavioral analyses of mutants for two odorant-binding protein genes, Obp57d and Obp57e, in Drosophila melanogaster. Genes Genet. Syst. 83:257-264.
50. Matsuo, T. (2008) Genes for host-plant selection in Drosophila. J. Neurogenetics 22:195-210
51. 松尾隆嗣 (2008) ショウジョウバエの食性の進化　細胞工学 27:1112-1117
52. Matsuno M, Horiuchi J, Tully T, Saitoe M. (2008) The Drosophila cell adhesion molecule klingon is required for long-term memory formation and is regulated by Notch. Proc Natl Acad Sci USA. 106, 310-315.
53. Horiuchi, J., Yamazaki, D., Naganos, S., Aigaki, T. and Saitoe, M. (2008) Protein kinase A inhibits a consolidated form of memory in Drosophila. Proc Natl Acad Sci USA. 105, 20976-20981.
54. List, O., Togawa, T., Tsuda, M., Matsuo, T., Elard, L. and Aigaki, T. (2009) Overexpression of grappa encoding a histone methyltransferase enhances stress resistance in Drosophila. Hereditas, 146, 19-28.
55. Suzuki, E., Zhao Y., Ito, S., Sawatsubashi, S., Murata, T., Furutani, T., Shirode, Y., Yamagata, K., Tanabe, M., Kimura, S., Ueda, T., Fujiyama, S., Lim, J., Matsukawa, H., Kouzmenko, AP., Aigaki, T., Tabata, T., Takeyama, KI, and Kato, S. (2009) Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity. Proc Natl Acad Sci USA.106, 3818-3822.
56. Ahsan, B., Saito, TL., Hashimoto, S., Muramatsu, K., Tsuda, M., Sasaki, A., Matsushima, K., Aigaki, T. and Morishita, S. (2009) MachiBase: a Drosophila melanogaster 5'-end mRNA transcription database. Nucleic Acids Res. 37, D49-53.
57. Shindo, M., Wada, H., Kaido, M., Tateno, M., Aigaki, T., Tsuda, L. and Hayashi, S. (2008) Dual function of Src in the maintenance of adherens junctions during tracheal epithelial morphogenesis. Development 135, 1355-1364
58. 木下善仁，津田学，相垣敏郎 (2008) TCA回路を中心とした代謝調節と寿命制御，基礎老化研究 32, 21-23.
59. Kaji, K., Tomino, S., and Asano, T. (2009) A serine protease in the midgut of the silkworm, Bombyx mori: Protein sequencing, identification of cDNA, demonstration of its synthesis as zymogen form and activation during midgut remodeling. Insect Biochem and Mol biol. 39. 207-17.
60. Asano, T. and Takebuchi, K. (2009) Identification of the gene encoding pro-phenoloxidase A3 in the fruitfly, Drosophila melanogaster. Insect Mol Biol. 18, 223-232
61. Nam, H-J. Jang, I-H., Asano, T. and Lee, W-J. (2008) Involvement of pro-phenoloxidase 3 in lamellocyte-meidated spontaneous melanization in Drosophila. Molecular and Cells. 2008. 2, .606-610
62. Yao, Y., Wu, Y., Yin, C., Ozawa, R., Aigaki, T., Wouda, R.R., Noordermeer, J.N., Fradkin, L.G., Hing, H. (2007) Antagonistic roles of Wnt5 and the Drl receptor in patterning the Drosophila antennal lobe. Nat Neurosci. 10, 1423-1432
63. Taniguchi K, Hozumi S, Maeda R, Ooike M, Sasamura T, Aigaki T, Matsuno K. (2007) D-JNK signaling in visceral muscle cells controls the laterality of the Drosophila gut. Dev Biol. 311, 251-263
64. Tsuda M, Sugiura T, Ishii T, Ishii N, Aigaki T. (2007) A mev-1-like dominant-negative SdhC increases oxidative stress and reduces lifespan in Drosophila. Biochem Biophys Res Commun. 363, 342-346.
65. Sakurai T, K., Kojima, T., Aigaki, T., *Hayashi, S (2007) Differential control of cell affinity required for progression and refinement of cell boundary during Drosophila leg segmentation, Dev Biol, 309, 126-136
66. Matsuo, T., Sugaya, S., Yasukawa, J., Aigaki, T., Fuyama, Y. (2007) Odorant-Binding Proteins OBP57d and OBP57e Affect Taste Perception and Host-Plant Preference in Drosophila sechellia. PLoS Biology. 5(5):e118
67. Umeda-Kameyama, Y., Tsuda, M., Ohkura, C., Matsuo, T., Namba, Y., Ohuchi, Y. and Aigaki, T. (2007) Thioredoxin suppresses Pael-R-induced neurotoxicity and extends longevity in Drosophila. J. Biol. Chem. 282, 11180-11187.
68. Shima, S., Aigaki, T., Nojima, T. and Yamamoto, D. (2007) Identification of trf2 mutants of Drosophila with defects in anterior spiracle eversion. Arch. Insect Biochem. Physiol. 64, 157-163.