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 Jeon
  • Eun Ae Jeong
  • Sun-Young Park
  • Hyeonwi Son
  • Hyun Joo Shin
  • Dong Hoon Lee
  • Hyun Joon Kim
  • Sang Soo Kang
  • Gyeong Jae Cho
  • Wan Sung Choi
  • Gu Seob Roh
Original Article

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 

Supplementary material

12640_2012_9339_MOESM1_ESM.tif (2.3 mb)
Supplementary Fig. 1Effect of Y-27632 pretreatment on neuroprotection in the mouse hippocampus 7 days after KA administration (A) Representative microphotographs of cresyl violet, TUNEL, and FJB in the mouse hippocampus 7 days after KA injection. The numbers of TUNEL- (B) and FJB-positive cells (C) in the CA3 region. Arrow indicates a dying neuron with pyknotic nucleus and scant cytoplasm. Scale bar = 100 μm. (TIFF 2321 kb)
12640_2012_9339_MOESM2_ESM.tif (2.4 mb)
Supplementary Fig. 2Effect of Y39983 pretreatment on neuroprotection in glutamate-treated HT22 cells. (A) HT22 cells were incubated in the presence or absence of Y39983 (MedChemexpress Co., Shanghai, China) for 1 h. (B) Effect of Y39983 on glutamate-treated HT22 cell viability. (C) Representative photomicrographs showing the effect of Y39983 on cell viability of glutamate-treated HT22 cells. (TIFF 2427 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Byeong Tak Jeon
    • 1
  • Eun Ae Jeong
    • 1
  • Sun-Young Park
    • 2
  • Hyeonwi Son
    • 1
  • Hyun Joo Shin
    • 1
  • Dong Hoon Lee
    • 1
  • Hyun Joon Kim
    • 1
  • Sang Soo Kang
    • 1
  • Gyeong Jae Cho
    • 1
  • Wan Sung Choi
    • 1
  • Gu Seob Roh
    • 1
  1. 1.Department of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural DysfunctionGyeongsang National University School of MedicineJinjuRepublic of Korea
  2. 2.Department of Neurosurgery, Institute of Health Sciences, Medical Research Center for Neural DysfunctionGyeongsang National University School of MedicineJinjuRepublic of Korea

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