Testing the microglial activation hypothesis of schizophrenia using perinatal asphyxia model of rats

• Project/Area Number: 24591702
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: TAKAHASHI Taro 浜松医科大学, 医学部, 特任助教 (30402358)
• Co-Investigator(Kenkyū-buntansha): WAKUDA Tomoyasu 浜松医科大学, 精神医学講座, 助教 (80444355) ; IWATA Keiko 福井大学, 子どものこころの発達研究センター, 特命助教 (30415088)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 統合失調症 / ミクログリア / 周産期仮死 / 周産期仮死モデル / 産科合併症 / 胎生期感染モデル / poly I:C

Outline of Final Research Achievements

Epidemiological studies suggest that hypoxia-related perinatal complications increase the risk of schizophrenia. Neuropathological and neuroimaging studies of the disorder have indicated that immunological events such as overt microglial activation might underpin the development of schizophrenia. We hypothesized that birth complications that cause hypoxia in the fetal brain may be associated with dysregulation in the expression of susceptibility genes of schizophrenia and increased microglial activation. To test this, we examined these points in rat model of perinatal asphyxia. We found significantly altered expression of NRG1 and COMT in the mPFC. However, microglial activation was not detected at any developmental periods examined. Although these results failed to support the microglial activation hypothesis of schizophrenia, the results did suggest that perinatal asphyxia may lead to a long-lasting influence on the expression of specific genes, such as NRG1 and COMT.

Research Products

• [Journal Article] Perinatal asphyxia alters neuregulin-1 and COMT gene expression in the medial prefrontal cortex in rats. (2015)
  • Author(s): Wakuda T, Iwata K, Iwata Y, Anitha A, Takahashi T, Yamada K, Vasu MM, Matsuzaki H, Suzuki K, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. Volume: 56 Pages: 149-154
  • DOI: 10.1016/j.pnpbp.2014.08.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism. (2014)
  • Author(s): 1.Iwata K, Matsuzaki H, Tachibana T, Ohno K, Yoshimura S, Takamura H, Yamada K, Matsuzaki S, Nakamura K, Tsuchiya KJ, Matsumoto K, Tsujii M, Sugiyama T, Katayama T, Mori N
  • Journal Title: Molecular Autism Volume: 5(33) Issue: 1 Pages: 2040-2392
  • DOI: 10.1186/2040-2392-5-33
  • Peer Reviewed / Open Access
• [Journal Article] Vldlr overexpression causes hyperactivity in rats. (2012)
  • Author(s): Iwata K
  • Journal Title: Mol Autism. Volume: 3 Issue: 1 Pages: 11-11
  • DOI: 10.1186/2040-2392-3-11
  • Peer Reviewed