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 HuangEmail author


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.


Seizures Neuronal excitability PPAR-γ Pioglitazone Pilocarpine 



This work was supported in part by grants from the Taiwan National Science Council (NSC-102-2314-B-006-051-MY3), Ministry of Science and Technology, ROC, (105-2314-B-006-013, 106-2314-B-006-034, 106-2320-B-006-055, 107-2314-B-006-018, 107-2320-B-006-019), National Cheng Kung University Hospital (20180254), and Chi-Mei Medical Center (CMNCKU10303). Part of this abstract was presented at the Taiwan Neurological Society Annual Meeting, 2013.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.


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Authors and Affiliations

  1. 1.Department of PediatricsChi-Mei Medical CenterTainanTaiwan
  2. 2.Institute of Clinical MedicineNational Cheng Kung University College of MedicineTainanTaiwan
  3. 3.Graduate Institute of Biomedical SciencesChina Medical UniversityTaichungTaiwan
  4. 4.Translational Medicine Research CenterChina Medical University HospitalTaichungTaiwan
  5. 5.Department of PhysiologyNational Cheng Kung University College of MedicineTainanTaiwan
  6. 6.Department of Neurology, National Cheng Kung University Hospital, College of MedicineNational Cheng Kung UniversityTainanTaiwan

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