| First Author | Shin HJ | Year | 2014 |
| Journal | Cell Death Differ | Volume | 21 |
| Issue | 7 | Pages | 1095-106 |
| PubMed ID | 24608792 | Mgi Jnum | J:229492 |
| Mgi Id | MGI:5752117 | Doi | 10.1038/cdd.2014.29 |
| Citation | Shin HJ, et al. (2014) Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-kappaB-mediated neuroinflammation in kainic acid-induced seizures. Cell Death Differ 21(7):1095-106 |
| abstractText | 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-kappaB 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. |
