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Author

Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-kappa B-mediated neuroinflammation in kainic acid-induced seizures

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Title
Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-kappa B-mediated neuroinflammation in kainic acid-induced seizures
Author
Shin, H.J.Kim, H.Heo, R.W.Kim, H.J.Choi, W.S.Kwon, H. MooRoh, G.S.
Keywords
TRANSCRIPTION FACTOR NFAT5; TEMPORAL-LOBE EPILEPSY; STATUS EPILEPTICUS; BRAIN-DAMAGE; RAT-BRAIN; SYSTEMIC HYPERTONICITY; MOUSE HIPPOCAMPUS; WATER CHANNELS; NEURONAL DEATH; EXPRESSION
Issue Date
201407
Publisher
NATURE PUBLISHING GROUP
Citation
CELL DEATH AND DIFFERENTIATION, v.21, no.7, pp.1095 - 1106
Abstract
Kainic acid (KA)-induced seizures followed by neuronal death are associated with neuroinflammation and blood-brain barrier (BBB) leakage. Tonicity-responsive enhancer binding protein (TonEBP) is known as a transcriptional factor activating osmoprotective genes, and in brain, it is expressed in neuronal nuclei. Thus dysregulation of TonEBP may be involved in the pathology of KA-induced seizures. Here we used TonEBP heterozygote (+/-) mice to study the roles of TonEBP. Electroencephalographic study showed that TonEBP (+/-) mice reduced seizure frequency and severity compared with wild type during KA-induced status epilepticus. Immunohistochemistry and western blotting analysis showed that KA-induced neuroinflammation and BBB leakage were dramatically reduced in TonEBP (+/-) mice. Similarly, TonEBP-specific siRNA reduced glutamate-induced death in HT22 hippocampal neuronal cells. TonEBP haplodeficiency prevented KA-induced nuclear translocation of NF-κB p65 and attenuated inflammation. Our findings identify TonEBP as a critical regulator of neuroinflammation and BBB leakage in KA-induced seizures, which suggests TonEBP as a good therapeutic target.
URI
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DOI
http://dx.doi.org/10.1038/cdd.2014.29
ISSN
1350-9047
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