The influence of anesthetic agent on the plasty of neuronal circuit in the developmental brain

• Project/Area Number: 15K10528
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: National Defense Medical College
• Principal Investigator: Kodama Mitsuyoshi 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 病院 麻酔科, 講師 (00597528)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); 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)
• Keywords: 麻酔薬 / 発達期脳神経 / 毒性 / 脳神経 / 麻酔 / 神経 / 管状輸送

Outline of Final Research Achievements

Propofol increased RhoA activation, collapsed growth cones, and impaired retrograde axonal transport ofquantum dot-labelled brain-derived neurotrophic factor, all of which were prevented with TAT-C3. Adult mice previously treated with propofol had decreased numbers of total hippocampal synapses and presynaptic vesicles, reduced hippocampal dendritic arborisation, and infrapyramidal mossy fibres. These mice also exhibited decreased hippocampaldependent contextual fear memory recall. All anatomical and behavioural changes were prevented with TAT-C3 pretreatment.

Research Products

• [Journal Article] Inhibition of RhoA reduces propofol-mediated growth cone collapse, axonal transport impairment, loss of synaptic connectivity, and behavioural deficits. (2018)
  • Author(s): Pearn ML, Schilling JM, Jian M, Egawa J, Wu C, Mandyam CD, Fannon-Pavlich MJ, Nguyen U, Bertoglio J, Kodama M, Mahata SK, DerMardirossian C, Lemkuil BP, Han R, Mobley WC, Patel HH, Patel PM, Head BP.
  • Journal Title: British Journal of Anaesthesia Volume: 120 Issue: 4 Pages: 745760-745760
  • DOI: 10.1016/j.bja.2017.12.033
  • Peer Reviewed