Original Article

Neurotoxicity Research

, Volume 23, Issue 3, pp 238-248

The Rho-Kinase (ROCK) Inhibitor Y-27632 Protects Against Excitotoxicity-Induced Neuronal Death In Vivo and In Vitro

  • Byeong Tak JeonAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Eun Ae JeongAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Sun-Young ParkAffiliated withDepartment of Neurosurgery, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Hyeonwi SonAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Hyun Joo ShinAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Dong Hoon LeeAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Hyun Joon KimAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Sang Soo KangAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
  • , Gyeong Jae ChoAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
    • , Wan Sung ChoiAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
    • , Gu Seob RohAffiliated withDepartment of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine Email author 

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Abstract

Rho-associated coil kinase (ROCK) inhibitors reportedly prevent neurodegeneration, and abnormal ROCK activation in the central nervous system induces neurite collapse and retraction. However, it is unclear whether the ROCK inhibitor Y-27632 directly protects hippocampal neurons from excitotoxicity. Here, we determined the effects of Y-27632 on neuroprotection following kainic acid (KA)-induced seizures in mice and during glutamate-induced excitotoxicity in HT22 cells. One day after Y-27632 injection, mice were treated with KA and killed 1–2 days later. Fluoro-Jade B and rapid Golgi staining showed that Y-27632 protected against KA-induced neurodegeneration and neurite dystrophy. Y-27632 inhibited increases in hippocampal RhoA and ROCK2 in KA-treated mice as determined by western blot analysis. Immunohistochemical analysis revealed ROCK2-positive neurons and astrocytes in the KA-treated hippocampus. In HT22 cells, Y-27632 also protected neurons and neurite formation during glutamate-induced excitotoxicity in vitro. These results indicate that ROCK inhibition modulates neurite growth and protects neurons from excitotoxicity-induced cell death.

Keywords

Y-27632 Excitotoxicity Rho kinase Neuron