Mechanism underlying the biological clock dysfunction-induced onset of mood disorder and hippocampal neurogenesis upregulation

• Project/Area Number: 26461709
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Tohoku University
• Principal Investigator: Kurita Masatake 東北大学, 薬学研究科, 分野研究員 (10423790)
• Co-Investigator(Kenkyū-buntansha): 守屋 孝洋 東北大学, 薬学研究科, 准教授 (80298207)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 時計遺伝子 / Clock / 気分障害 / 神経幹細胞 / 海馬ニューロン新生

Outline of Final Research Achievements

It is well known that the circadian rhythm dysregulation is associated with onset of mood disorder in human. In this study, we investigated the effects of clock gene mutation on the hippocampal neurogenesis and tried to clarify the underlying molecular mechanism. We found that clock mutant showed the mania-like behaviour of mice and hypersensitivity to EGF of cultured neural stem cells. The detailed assay revealed that clock mutaion altered EGF-induced acute changes in clock-related genes as well as the cell cycle-related genes in the neural stem cells. These findings suggest that the molecular clock in the neural stem cells causally involve the onset of mood disorder via regulation the cell cycle conditions.

Research Products

• [Journal Article] Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity (2017)
  • Author(s): Okuda-Tanino A, Sugawara D, Tashiro T, Iwashita M, Obara Y, Moriya T, Tsushima C, Saigusa D, Tomioka Y, Ishii K, Nakahata N
  • Journal Title: PLoS One Volume: 12 Issue: 3 Pages: e0173628-e0173628
  • DOI: 10.1371/journal.pone.0173628
  • Peer Reviewed / Open Access
• [Journal Article] Yokukansan improves behavioral and psychological symptoms of dementia by suppressing dopaminergic function. (2016)
  • Author(s): Takeyoshi K, Kurita M, Nishino S, Teranishi M, Numata Y, Sato T, Okubo Y.
  • Journal Title: Neuropsychiatr Dis Treat. Volume: 12 Pages: 641-9
  • DOI: 10.2147/ndt.s99032
  • Peer Reviewed / Open Access
• [Journal Article] Non-24-hour sleep-wake syndrome improved by low-dose valproic acid: a case report (2016)
  • Author(s): Kurita M, Moriya T, Nishino S, Hirata E, Hirasawa N, Okubo Y, Sato T
  • Journal Title: Neuropsychiatr Dis Treat Volume: 12 Pages: 3199-3203
  • DOI: 10.2147/ndt.s115648
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] BE360, a new selective estrogen receptor modulator, produces antidepressant and antidementia effects through the enhancement of hippocampal cell proliferation in olfactory bulbectomized mice. (2016)
  • Author(s): Osamu Nakagawasai, Wataru Nemoto, Hiroshi Onogi, Takahiro Moriya, Jia-Rong Lin, Takayo Odaira, Fukie Yaoita, Takumi Ogawa, Kiminori Ohta, Yasuyuki Endo, Koichi Tan-No
  • Journal Title: Behav Brain Res Volume: 297 Pages: 315-322
  • DOI: 10.1016/j.bbr.2015.10.033
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ROLE OF CLOCK GENE IN THE HIPPOCAMPAL NEUROGENESIS (2014)
  • Author(s): Jun Takoda, Shiori Sudo, Asuka Mogi, Hiromu Fukuzawa, Masatake Kurita, Tokiko Suzuki, Shigenobu Shibata, Takahiro Moriya
  • Organizer: The 2nd Taiwan-Tohoku univeristy Neuroscience Workshop for Young Scientists
  • Place of Presentation: 宮城県蔵王町
  • Year and Date: 2014-12-07 – 2014-12-10