Development of neuroprotective therapy for amyotrophic lateral sclerosis using serotonergic reagent

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659431
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: ASANUMA Masato 岡山大学, 医歯(薬)学総合研究科, 教授 (00273970)
• Co-Investigator(Kenkyū-buntansha): MIYAZAKI Ikuko 岡山大学, 大学院医歯薬学総合研究科, 助教 (40335633)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 筋萎縮性側索硬化症 / アストロサイト / セロトニン / 運動障害 / メタロチオネイン

Outline of Final Research Achievements

We examined neuroprotective effects of serotonin-1A receptor agonist 8-OH-DPAT on progressive motor neuron degeneration in amyotrophic lateral sclerosis (ALS) model mice and in primary culture cells. The pre-treatments of 8-OH-DPAT prior to onset of motor symptoms delayed disease onset. The chronic post-treatments of the drug after the onset significantly inhibited disease progression and showed protective effects on motor neuron loss in the cervical and lumber spinal cords in the ALS models. Furthermore, we revealed that the neuroprotective effects are based, in part, on expression and release of metallothionein in/from astrocytes via serotonin-1A receptors and sequent activation of transcription factor Nrf2.

Free Research Field

神経薬理化学