The Protective Role of Peroxisome Proliferator-Activated Receptor-Gamma in Seizure and Neuronal Excitotoxicity

Te Yu Hung, Fang Liang Chu, Dong Chuan Wu, Sheng Nan Wu, Chin Wei Huang

研究成果: Article同行評審

25 引文 斯高帕斯(Scopus)

摘要

The peroxisome proliferator-activated receptor (PPAR) family, type II nucleus receptors have been successfully tested for their neuroprotective potential in certain central nervous system diseases. The aim of the present study was to determine if modulation by PPAR-γ could attenuate pilocarpine-induced seizures and decrease neuronal excitability. Adult male C57BL/6 mice were divided into two groups: one group received pretreatment with pioglitazone and the other received dimethyl sulfoxide (DMSO) for a period of 2 weeks. Status epilepticus was then induced in both groups by lithium-pilocarpine, after which seizure susceptibility, severity, and mortality were evaluated. Hippocampal histopathology was carried out on all mice at 24 h post-status epilepticus as well as blood–brain barrier (BBB) damage analysis. With the aid of patch clamp technology, the hippocampal neuronal excitability from mice with PPAR-γ 50% expression (PpargC/C) and PPAR-γ 25% expression (PpargC/−), as well as the effect of pioglitazone on the sodium currents in hippocampal neurons, were evaluated. It was found that pioglitazone, a PPAR-γ agonist, could attenuate pilocarpine-induced seizure severity in mice. Pathological examination showed that pioglitazone significantly attenuated pilocarpine-induced status epilepticus-related hippocampal neuronal loss and BBB damage. Further characterization of neuronal excitability revealed higher excitability in the brain slices from mice with PpargC/− expression, compared with the PpargC/C group. It was also found that pioglitazone could decrease sodium currents in hippocampal neurons. In conclusion, PPAR-γ deficiency aggravated neuronal excitability and excitotoxicity. PPAR-γ attenuated pilocarpine-induced seizure severity, neuronal loss, BBB damage, and sodium currents in hippocampal neurons. Modulation of PPAR-γ could be a potential novel treatment for epileptic seizures.

原文English
頁(從 - 到)5497-5506
頁數10
期刊Molecular Neurobiology
56
發行號8
DOIs
出版狀態Published - 2019 8月 15

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 細胞與分子神經科學

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